CDC 78668 DS1

Toxicological Profile for
Endrin
Draft for Public Comment
May 2019
ENDRIN ii
DISCLAIMER
Use of trade names is for identification only and does not imply endorsement by the Agency for Toxic
Substances and Disease Registry, the Public Health Service, or the U.S. Department of Health and Human
Services.
This information is distributed solely for the purpose of pre dissemination public comment under
applicable information quality guidelines. It has not been formally disseminated by the Agency for Toxic
Substances and Disease Registry. It does not represent and should not be construed to represent any
agency determination or policy.
***DRAFT FOR PUBLIC COMMENT***

ENDRIN iii
FOREWORD
This toxicological profile is prepared in accordance with guidelines developed by the Agency for Toxic
Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The
original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised
and republished as necessary.
The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects
information for these toxic substances described therein. Each peer-reviewed profile identifies and
reviews the key literature that describes a substance's toxicologic properties. Other pertinent literature is
also presented, but is described in less detail than the key studies. The profile is not intended to be an
exhaustive document; however, more comprehensive sources of specialty information are referenced.
The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile
begins with a relevance to public health discussion which would allow a public health professional to
make a real-time determination of whether the presence of a particular substance in the environment
poses a potential threat to human health. The adequacy of information to determine a substance's health
effects is described in a health effects summary. Data needs that are of significance to the protection of
public health are identified by ATSDR and EPA.
Each profile includes the following:

(A) The examination, summary, and interpretation of available toxicologic information and
epidemiologic evaluations on a toxic substance to ascertain the levels of significant human
exposure for the substance and the associated acute, intermediate, and chronic health effects;
(B) A determination of whether adequate information on the health effects of each substance is
available or in the process of development to determine the levels of exposure that present a
significant risk to human health due to acute, intermediate, and chronic duration exposures;
and
(C) Where appropriate, identification of toxicologic testing needed to identify the types or levels
of exposure that may present significant risk of adverse health effects in humans.
The principal audiences for the toxicological profiles are health professionals at the Federal, State, and
local levels; interested private sector organizations and groups; and members of the public. ATSDR plans
to revise these documents in response to public comments and as additional data become available.
Therefore, we encourage comments that will make the toxicological profile series of the greatest use.
Electronic comments may be submitted via: www.regulations.gov. Follow the on-line instructions for
submitting comments.
Written comments may also be sent to: Agency for Toxic Substances and Disease Registry
Division of Toxicology and Human Health Sciences
Environmental Toxicology Branch
1600 Clifton Road, N.E.
Mail Stop S102-1
Atlanta, Georgia 30329-4027

ENDRIN iv
The toxicological profiles are developed under the Comprehensive Environmental Response,
Compensation, and Liability Act of 1980, as amended (CERCLA or Superfund). CERCLA section
104(i)(1) directs the Administrator of ATSDR to “…effectuate and implement the health related
authorities” of the statute. This includes the preparation of toxicological profiles for hazardous
substances most commonly found at facilities on the CERCLA National Priorities List (NPL) and that
pose the most significant potential threat to human health, as determined by ATSDR and the EPA.
Section 104(i)(3) of CERCLA, as amended, directs the Administrator of ATSDR to prepare a
toxicological profile for each substance on the list. In addition, ATSDR has the authority to prepare
toxicological profiles for substances not found at sites on the NPL, in an effort to “…establish and
maintain inventory of literature, research, and studies on the health effects of toxic substances” under
CERCLA Section 104(i)(1)(B), to respond to requests for consultation under section 104(i)(4), and as
otherwise necessary to support the site-specific response actions conducted by ATSDR.
This profile reflects ATSDR’s assessment of all relevant toxicologic testing and information that has been
peer-reviewed. Staffs of the Centers for Disease Control and Prevention and other Federal scientists have
also reviewed the profile. In addition, this profile has been peer-reviewed by a nongovernmental panel
and is being made available for public review. Final responsibility for the contents and views expressed
in this toxicological profile resides with ATSDR.
Patrick N. Breysse, Ph.D., CIH

Director, National Center for Environmental Health and
Agency for Toxic Substances and Disease Registry
Centers for Disease Control and Prevention

ENDRIN v
VERSION HISTORY
Date Description
May 2019 Update of data in Chapters 2, 3, and 7
August 1996 Final toxicological profile released

ENDRIN vi
CONTRIBUTORS & REVIEWERS
CHEMICAL MANAGER TEAM
Susan Zells Ingber, AB, MSPP (Lead) Kimberly Zaccaria, Ph.D., D.A.B.T.
Lisa Ingerman, Ph.D., D.A.B.T.
ATSDR, Division of Toxicology and Human Health SRC, Inc., North Syracuse, NY
Sciences, Atlanta, GA
REVIEWERS
Interagency Minimal Risk Level Workgroup:

Includes ATSDR; National Center for Environmental Health (NCEH); National Institute of
Occupational Health and Safety (NIOSH); U.S. Environmental Protection Agency (EPA); National
Toxicology Program (NTP).
Additional reviews for science and/or policy:

ATSDR, Division of Community Health Investigations; ATSDR, Office of Science; NCEH, Division of
Laboratory Science; NCEH, Division of Environmental Health Science and Practice.
PEER REVIEWERS
1. Jonathan Doorn, Ph.D., Associate Professor, College of Pharmacy, Division of Medicinal and
Natural Products Chemistry, Division Head, Medicinal and Natural Products Chemistry, The
University of Iowa, Iowa City, Iowa
2. J.E. Klaunig, Ph.D., Fellow ATS, Fellow IATP, Professor, Environmental Health, Professor,
School of Public and Environmental Affairs, Indiana University Bloomington, Bloomington,
Indiana
3. Debasis Bagchi, Ph.D., MACN, CNS, MAIChE, Chief Scientific Officer at Cepham Research
Center, Industry Pharmaceuticals, San Francisco, California
These experts collectively have knowledge of toxicology, chemistry, and/or health effects. All reviewers
were selected in conformity with Section 104(I)(13) of the Comprehensive Environmental Response,
Compensation, and Liability Act, as amended.
ATSDR scientists review peer reviewers’ comments and determine whether changes will be made to the
profile based on comments. The peer reviewers’ comments and responses to these comments are part of
the administrative record for this compound.
The listing of peer reviewers should not be understood to imply their approval of the profile's final
content. The responsibility for the content of this profile lies with ATSDR.

ENDRIN vii
CONTENTS
DISCLAIMER .............................................................................................................................................. ii
FOREWORD ............................................................................................................................................... iii
VERSION HISTORY ................................................................................................................................... v
CONTRIBUTORS & REVIEWERS ........................................................................................................... vi
CONTENTS................................................................................................................................................ vii
LIST OF FIGURES ..................................................................................................................................... ix
LIST OF TABLES ........................................................................................................................................ x
CHAPTER 1. RELEVANCE TO PUBLIC HEALTH ................................................................................ 1

1.1 OVERVIEW AND U.S. EXPOSURES ......................................................................................... 1
1.2 SUMMARY OF HEALTH EFFECTS........................................................................................... 1
1.3 MINIMAL RISK LEVELS (MRLs) .............................................................................................. 6
CHAPTER 2. HEALTH EFFECTS ............................................................................................................. 9

2.1 INTRODUCTION .......................................................................................................................... 9
2.2 DEATH ........................................................................................................................................ 44
2.3 BODY WEIGHT .......................................................................................................................... 46
2.4 RESPIRATORY .......................................................................................................................... 46
2.5 CARDIOVASCULAR ................................................................................................................. 47
2.6 GASTROINTESTINAL............................................................................................................... 48
2.7 HEMATOLOGICAL ................................................................................................................... 48
2.8 MUSCULOSKELETAL .............................................................................................................. 49
2.9 HEPATIC ..................................................................................................................................... 49
2.10 RENAL ........................................................................................................................................ 53
2.11 DERMAL ..................................................................................................................................... 54
2.12 OCULAR ..................................................................................................................................... 54
2.13 ENDOCRINE ............................................................................................................................... 54
2.14 IMMUNOLOGICAL ................................................................................................................... 56
2.15 NEUROLOGICAL....................................................................................................................... 56
2.16 REPRODUCTIVE ....................................................................................................................... 60
2.17 DEVELOPMENTAL ................................................................................................................... 61
2.18 OTHER NONCANCER ............................................................................................................... 64
2.19 CANCER...................................................................................................................................... 64
2.20 GENOTOXICITY ........................................................................................................................ 65
2.21 MECHANISMS OF TOXICITY ................................................................................................. 68
CHAPTER 3. TOXICOKINETICS, SUSCEPTIBLE POPULATIONS, BIOMARKERS, CHEMICAL

INTERACTIONS ............................................................................................................... 70
3.1 TOXICOKINETICS..................................................................................................................... 70
3.1.1 Absorption ............................................................................................................................. 70
3.1.2 Distribution ........................................................................................................................... 71
3.1.3 Metabolism............................................................................................................................ 72
3.1.4 Excretion ............................................................................................................................... 74
3.1.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models ............. 75
3.1.6 Animal-to-Human Extrapolations ......................................................................................... 76
3.2 CHILDREN AND OTHER POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE..... 76
3.3 BIOMARKERS OF EXPOSURE AND EFFECT ....................................................................... 77
3.3.1 Biomarkers of Exposure ........................................................................................................ 78
3.3.2 Biomarkers of Effect ............................................................................................................. 79

ENDRIN viii
3.4 INTERACTIONS WITH OTHER CHEMICALS ....................................................................... 79
CHAPTER 4. CHEMICAL AND PHYSICAL INFORMATION ............................................................ 81

4.1 CHEMICAL IDENTITY ............................................................................................................. 81
4.2 PHYSICAL AND CHEMICAL PROPERTIES .......................................................................... 81
CHAPTER 5. POTENTIAL FOR HUMAN EXPOSURE ........................................................................ 85

5.1 OVERVIEW ................................................................................................................................ 85
5.2 PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL .................................................. 86
5.2.1 Production ............................................................................................................................. 86
5.2.2 Import/Export ........................................................................................................................ 87
5.2.3 Use ........................................................................................................................................ 87
5.2.4 Disposal ................................................................................................................................. 87
5.3 RELEASES TO THE ENVIRONMENT ..................................................................................... 88
5.3.1 Air ......................................................................................................................................... 88
5.3.2 Water ..................................................................................................................................... 89
5.3.3 Soil ........................................................................................................................................ 89
5.4 ENVIRONMENTAL FATE ........................................................................................................ 90
5.4.1 Transport and Partitioning..................................................................................................... 90
5.4.2 Transformation and Degradation .......................................................................................... 93
5.5 LEVELS IN THE ENVIRONMENT ........................................................................................... 96
5.5.1 Air ......................................................................................................................................... 98
5.5.2 Water ..................................................................................................................................... 99
5.5.3 Sediment and Soil ............................................................................................................... 100
5.5.4 Other Media ........................................................................................................................ 102
5.6 GENERAL POPULATION EXPOSURE.................................................................................. 105
5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES .............................................. 109
CHAPTER 6. ADEQUACY OF THE DATABASE ............................................................................... 110

6.1 Information on Health Effects .................................................................................................... 110
6.2 Identification of Data Needs ...................................................................................................... 112
6.3 Ongoing Studies ......................................................................................................................... 118
CHAPTER 7. REGULATIONS AND GUIDELINES ............................................................................ 119
CHAPTER 8. REFERENCES ................................................................................................................. 121
APPENDICES
APPENDIX A. ATSDR MINIMAL RISK LEVELS AND WORKSHEETS......................................... A-1
APPENDIX B. LITERATURE SEARCH FRAMEWORK FOR ENDRIN ........................................... B-1
APPENDIX C. USER’S GUIDE ............................................................................................................. C-1
APPENDIX D. QUICK REFERENCE FOR HEALTH CARE PROVIDERS ....................................... D-1
APPENDIX E. GLOSSARY ................................................................................................................... E-1
APPENDIX F. ACRONYMS, ABBREVIATIONS, AND SYMBOLS .................................................. F-1

ENDRIN ix
LIST OF FIGURES
1-1. Health Effects Found in Animals Following Oral Exposure to Endrin ................................................ 3
1-2. Summary of Sensitive Targets of Endrin – Oral................................................................................... 7
2-1. Overview of the Number of Studies Examining Endrin Health Effects ............................................. 12
2-2. Levels of Significant Exposure to Endrin – Inhalation....................................................................... 22
2-3. Levels of Significant Exposure to Endrin/Endrin Aldehyde/Endrin Ketone – Oral ........................... 38
3-1. Proposed Metabolism Scheme for Endrin in Mammals ..................................................................... 73
5-1. Number of NPL Sites with Endrin Contamination ............................................................................. 85
6-1. Summary of Existing Health Effects Studies on Endrin By Route and Endpoint ............................ 111

ENDRIN x
LIST OF TABLES
1-1. Minimal Risk Levels (MRLs) for Endrin ............................................................................................. 8
2-1. Health Effects in Humans Exposed to Endrin—Epidemiological Studies ......................................... 13
2-2. Levels of Significant Exposure to Endrin – Inhalation....................................................................... 21
2-3. Levels of Significant Exposure to Endrin/Endrin Aldehyde/Endrin Ketone – Oral ........................... 23
2-4. Levels of Significant Exposure to Endrin – Dermal ........................................................................... 43
2-5. Genotoxicity of Endrin In Vitro .......................................................................................................... 65
2-6. Genotoxicity of Endrin In Vivo........................................................................................................... 67
4-1. Chemical Identity of Endrin, Endrin Aldehyde, and Endrin Ketone .................................................. 82
4-2. Physical and Chemical Properties of Endrin, Endrin Aldehyde, and Endrin Ketone ......................... 83
5-1. Bioconcentration Data for Endrin ....................................................................................................... 91
5-2. Lowest Limit of Detection Based on Standards ................................................................................. 97
5-3. Endrin, Endrin Aldehyde and Endrin Ketone Levels in Water, Soil, and Air of National
Priorities List (NPL) Sites .................................................................................................................. 97
5-4. Serum Endrin Levels (Lipid-Adjusted) in the NHANES U.S. Population ....................................... 107
7-1. Regulations and Guidelines Applicable to Endrin............................................................................ 119

ENDRIN 1
CHAPTER 1. RELEVANCE TO PUBLIC HEALTH
1.1 OVERVIEW AND U.S. EXPOSURES
ATSDR’s Toxicological Profile for Endrin was released in 1996. In order to update the literature in this
profile, ATSDR conducted a literature search focused on health effects information as described in
Appendix B. Chapters 2, 3, and 7 were revised to reflect the most current health effects and
regulations/guidelines data. In some cases, other sections of the profile were updated as needed or for
consistency with the updated health effects data. However, the focus of the update to this profile is on
health effects information.
Endrin [2,7:3,6-dimethanonaphth(2,3-b)oxirene, 3,4,5,6,9,9-hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-

(1aα,2β,2aβ,3α,6α,6aβ,7β,7aα)-, CAS No. 72-20-8] was used as a pesticide. It has not been produced or
used in the United States since 1991 (Bishop 1984, 1985, 1986; EPA 1983e; USDA 1995), which greatly
reduces the potential for human exposure. This profile also covers endrin aldehyde and endrin ketone,
which were never commercial products, but occurred as impurities of endrin or as degradation products
(EPA 1985e; IARC 1974; SRI 1987). Because the United States no longer produces or uses endrin,
future levels of endrin, endrin aldehyde, and endrin ketone in environmental media are expected to be
low. The most significant route of exposure is most likely ingestion of imported foods contaminated with
endrin; however, there may also be some localized risks from exposures near waste disposal sites or from
groundwater contaminated with endrin.
Case reports of endrin toxicity in humans suggest that endrin is readily absorbed following ingestion and,
as evidenced by accounts in the occupational setting, dermal exposure. Limited data in animals suggest
that endrin is also quickly absorbed following inhalation exposure. Endrin is rapidly metabolized and
excreted in the urine and feces. However, low concentrations of endrin may remain in adipose tissue
following high exposures.
1.2 SUMMARY OF HEALTH EFFECTS
Information on the noncancer toxicity of endrin comes primarily from oral studies in animals; however,
several occupational surveys and case reports in exposed humans contribute to the identification of
primary toxicity targets. Sixty-three laboratory animal toxicity studies with health effects data have been
identified: 2 inhalation, 57 oral, and 4 dermal.

ENDRIN 2
1. RELEVANCE TO PUBLIC HEALTH
As illustrated in Figure 1-1, the most sensitive effects in laboratory animals appear to be neurological
effects (e.g., altered activity, convulsions) and hepatic toxicity. Other noncancer toxicity effects are
generally only observed at doses associated with lethality, including diffuse organ damage (lungs, heart,
kidney, endocrine glands) and body weight effects. With the exception of altered locomotor activity in
offspring, developmental effects were only observed at doses that caused significant maternal mortality
and/or toxicity. Data regarding these effects are discussed briefly below. Available data following
exposure to endrin in humans and animals are inadequate to determine the potential for adverse effects in
the gastrointestinal, hematological, musculoskeletal, ocular, dermal, immunological, or reproductive
systems.
Neurological Effects. Based on human reports, the central nervous system is the primary target system
of endrin. Acute human poisonings by endrin were characterized by symptoms of central nervous system
toxicity such as jerking of arms and legs, twitching facial muscles, tonic and clonic contractions,
convulsions and sudden collapse, and death (Carbajal-Rodriquez et al. 1990; Coble et al. 1967; Curley et
al. 1970; Davies and Lewis 1956; Rowley et al. 1987; Runhaar et al. 1985; Waller et al. 1992; Weeks
1967). Numerous case reports of convulsions following acute, high-level exposure have been reported in
workers that manufacture endrin; changes in electroencephalogram (EEG) patterns were usually observed
in these cases (Hoogendam et al. 1962, 1965).
Neurological effects occurred consistently in animals exposed to endrin via inhalation, oral, and dermal
exposure. Reported findings included behavioral effects (e.g., altered activity) and frank neurotoxic
effects (e.g., tremors and convulsions) (Chernoff et al. 1979a; Deichmann et al. 1970; Gaines 1960;
Kavlock et al. 1981; Kettering 1969, 1971; Lawrence et al. 1968; Mehrotra et al. 1989; NCI 1978; Pandey
1978; Speck and Maaske 1958; Treon et al. 1955), with altered EEG and diffuse brain lesions observed at
lethal levels (Ressang et al. 1959; Speck and Maaske 1958; Treon et al. 1955). Altered activity levels
have also been reported in rat and hamster offspring following maternal exposure to endrin (Gray et al.
1981).

ENDRIN 3
Figure 1-1. Health Effects Found in Animals Following Oral Exposure to Endrin

ENDRIN 4
Hepatic Effects. Human data on endrin-related hepatic effects are limited. The available human data
consist of an occupational survey of endrin workers reporting a few cases of increased serum levels of
liver enzymes (Hoogendam et al. 1965). However, only limited conclusions should be drawn from these
results, as the levels were within normal limits at subsequent evaluations (1 week–3 months later), despite
continued occupational exposure. Moreover, the study did not control for concurrent exposure to other
chemicals or alcohol. Studies involving several species of laboratory animals have consistently reported
hepatic effects following inhalation, oral, or dermal exposure at or near lethal levels. Effects included
increased liver weight, altered liver serum enzymes, diffuse degenerative lesions, necrosis, vacuolation,
fatty degeneration, and lipid peroxidation (Ali and Shakoori 1993; Bagchi et al. 1992a, 1992b, 1992c;
Hassan et al. 1991; Hassoun et al. 1993; Kavlock et al. 1981; Lawrence et al. 1968, Treon et al. 1955;
Young and Mehendale 1986). Chronic-duration oral studies in rats and dogs reported hepatic effects at
sublethal doses, including increased liver weight and/or cloudy swelling of centrilobular cells
(Deichmann et al. 1970; Kettering 1969; Treon et al. 1955).
Renal Effects. No human studies that assessed renal effects following endrin exposure were found.
Inhalation, oral, and dermal exposure to lethal levels of endrin caused diffuse degenerative lesions in the
kidneys of various species (Treon et al. 1955). Available laboratory animal studies have reported
inconsistent renal effects at sublethal exposure levels. A single study involving acute exposure to a high
dose reported renal histopathologic effects in rats, mice, and hamsters, including moderate tubular
necrosis and congestion, inflammation, and interstitial edema (Hassan et al. 1991). One chronic-duration
oral study in rats reported renal effects (cloudy swelling of tubule epithelial cells) at sublethal levels
(Deichmann et al. 1970). However, a 2-year bioassay did not observe any pathological renal effects in
rats or mice (NCI 1978) or dogs (Kettering 1969) following sublethal chronic doses.
Endocrine Effects. Several epidemiological studies have examined the potential relationship between
environmental endrin exposure and thyroid hormone levels in highly contaminated regions. In general,
only weak (if any) relationships were observed, and findings are inconsistent between studies, sexes, and
age groups (Freire et al. 2011, 2012, 2013; Piccoli et al. 2016). A potential increase in risk for Type I
diabetes was observed in children with high serum endrin levels; however, however, the study did not
adjust for any confounders, including other detectible pesticides (El Morsi et al. 2012). In laboratory
animals, thyroid hyperplasia and pituitary cysts were observed in rats, but not in mice or dogs, in chronic
bioassay studies with endrin administered in the feed (Kettering 1969; NCI 1978).

ENDRIN 5
Respiratory Effects. Limited human and animal data showed respiratory effects following endrin
exposure. Increased deaths due to pneumonia and other nonmalignant respiratory diseases were observed
in workers at one of two plants that manufactured endrin (Ditraglia et al. 1981). However, simultaneous
exposure to other chemicals occurred, and increased respiratory disease was not observed in the second
endrin manufacturing facility. Pulmonary edema was observed in a patient poisoned with endrin, but was
thought to be due to chemical pneumonitis from aspiration of aromatic hydrocarbons contained in the
formulation (Runhaar et al. 1985). Some rats chronically exposed to low dietary doses exhibited focal
hemorrhage and congestion of the lungs (Deichmann et al. 1970). Other histopathologic effects were
only observed in animals at lethal doses and were attributed to widespread systemic failure at lethal
exposure levels.
Cardiovascular Effects. Only limited reports of cardiovascular toxicity of endrin in animals were
located. Diffuse degenerative lesions of the heart were observed in some dogs administered lethal doses
of endrin, and enlarged hearts were observed at sublethal doses (Lawrence et al. 1968; Treon et al. 1955).
The health significance of these finding is unclear, as the effects were not observed in other animal
species.
Body Weight Effects. No specific effects on body weight have been noted in humans. Decreases in body
weight in animals were usually associated with administration of lethal doses and were not observed in
chronic toxicity studies (Chernoff et al. 1979a; Deichmann et al. 1970; Goldenthal 1978a; Kavlock et al.
1981; NCI 1978; Treon et al. 1955).
Developmental Effects. Available evidence in humans is inadequate to determine if endrin is associated

with adverse birth outcomes or male reproductive development (Fernandez et al. 2007; Samra and Selim
2009); however, one study reported an association between endrin exposure and cord blood thyroid
hormone levels (Freire et al. 2011). Prenatal exposure of animals to concentrations of endrin sufficient to
cause maternal toxicity has resulted in a statistically significant increase in the incidence of fused ribs,
cleft palate, exencephaly, meningoencephaloceles, and open eyes in hamsters and mice (Chernoff et al.
1979a; Kavlock et al. 1981, 1985; Ottolenghi et al. 1974). Effects were not necessarily reproducible
between studies (Goldenthal et al. 1978b), and were not observed in rats (Goldenthal et al. 1978a).
Increased motor activity has been observed in hamster offspring after gestational exposure to maternally
toxic doses (Gray et al. 1981). Adverse developmental effects generally have not been observed in rats
(Kavlock et al. 1981), except for a transient increase in locomotor activity of pups at low doses that were

ENDRIN 6
not toxic to the dam (Gray et al. 1981) and delayed ossification at doses that resulted in maternal toxicity
(Goldenthal 1978a).
Cancer. Studies of endrin-exposed workers have not detected significant increases in mortality due to
cancer (Ribbens 1985). In two industries manufacturing endrin, small excesses of certain cancers were
reported, including malignant neoplasms of the esophagus, rectum, liver, and lymphatic and
hematopoietic systems (Ditraglia et al. 1981). However, these findings were not statistically significant,
and the studies were limited by concurrent exposure to other chemicals. Endrin was reported to be
noncarcinogenic in animal studies (Deichmann et al. 1970; NCI 1978; Treon et al. 1955). Reuber (1978)
reported that endrin is carcinogenic; however, multiple reporting inconsistencies were identified,
observed tumors did not show a dose-related response, and Reuber’s criteria for classifying tissues as
tumorigenic were not consistent with those of other investigators (IRIS 2002).
The U.S. Environmental Protection Agency (EPA) has classified endrin in Group D, indicating there is
inadequate evidence to assess the potential carcinogenicity of endrin in humans (IRIS 2002). The
International Agency for Research on Cancer (IARC) has also determined that endrin was not classifiable
as to its carcinogenicity in humans (IARC 1987). The Department of Health and Human Services
(DHHS) (NTP 2016) has not classified the potential for endrin to cause cancer in humans.
1.3 MINIMAL RISK LEVELS (MRLs)
MRLs for inhalation exposure to endrin, endrin aldehyde, and endrin ketone were not derived for any
duration category because data are insufficient.
The oral database was considered adequate for deriving a provisional acute-duration MRL and a chronic-
duration MRL. An MRL was not derived for intermediate-duration oral exposure because the MRL
derived from the available data in the limited database would be higher than the provisional acute-
duration MRL. The provisional acute-duration MRL is expected to be protective of intermediate-duration
exposures; therefore, the provisional acute oral MRL is adopted as the provisional intermediate oral MRL.
As presented in Figure 1-2, the available oral data for endrin suggest that the central nervous system,
liver, and body weight effects are the most sensitive targets of toxicity in laboratory animals.
The MRL values are summarized in Table 1-1 and discussed in greater detail in Appendix A.

ENDRIN 7
Figure 1-2. Summary of Sensitive Targets of Endrin – Oral

The central nervous system and liver are the most sensitive targets of endrin oral exposure.
Numbers in circles are the lowest LOAELs for all health effects in animals.
No reliable dose response data were available for humans.

ENDRIN 8
Table 1-1. Minimal Risk Levels (MRLs) for Endrina
Exposure Point of Uncertainty

duration MRL Critical effect departure factor Reference
Inhalation exposure (ppm)
Acute Insufficient data for MRL derivation
Intermediate Insufficient data for MRL derivation
Chronic Insufficient data for MRL derivation
Oral exposure (mg/kg/day)
Acute 0.0006b Decreased locomotor 0.06 100 Kavlock et al.
activity (BMDL1SD) 1981
Intermediate Acute MRL is adopted as the intermediate MRLb
Chronic 0.0003 Convulsions, hepatic 0.025 100 Kettering
vacuolation (NOAEL) 1969
aSee Appendix A for additional information.

bProvisionalMRL.
BMDL = 95% lower confidence limit on the benchmark dose (subscripts denote benchmark response: i.e.,
1SD = exposure concentration associated with 1 standard deviation change in outcome); NOAEL = no-observed-
adverse-effect level

ENDRIN 9
CHAPTER 2. HEALTH EFFECTS
2.1 INTRODUCTION
The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and
other interested individuals and groups with an overall perspective on the toxicology of endrin. It
contains descriptions and evaluations of toxicological studies and epidemiological investigations and
provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health.
A glossary and list of acronyms, abbreviations, and symbols can be found at the end of this profile.
To help public health professionals and others address the needs of persons living or working near hazardous
waste sites, the information in this section is organized by health effect. These data are discussed in terms of
route of exposure (inhalation, oral, and dermal) and three exposure periods: acute (≤14 days), intermediate
(15–364 days), and chronic (≥365 days).
As discussed in Appendix B, a literature search was conducted to identify relevant studies examining health
effect endpoints. Figure 2-1 provides an overview of the database of studies in humans or experimental
animals included in this chapter of the profile. These studies evaluate the potential health effects associated
with inhalation, oral, or dermal exposure to endrin, but may not be inclusive of the entire body of literature.
Summaries of the human observational studies are presented in Table 2-1. Animal inhalation studies are
presented in Table 2-2 and Figure 2-2, animal oral studies are presented in Table 2-3 and Figure 2-3, and
animal dermal studies are presented in Table 2-4. For the inhalation and dermal tables (Table 2-2 and
Table 2-4, respectively), all studies evaluated endrin. For the oral table (Table 2-3), the experimental
compound (endrin, endrin ketone, or endrin aldehyde) is indicated for each study.
Levels of significant exposure (LSEs) for each route and duration are presented in tables and illustrated in
figures. The points in the figures showing no-observed-adverse-effect levels (NOAELs) or lowest-
observed-adverse-effect levels (LOAELs) reflect the actual doses (levels of exposure) used in the studies.
LOAELs have been classified into "less serious" or "serious" effects. "Serious" effects are those that
evoke failure in a biological system and can lead to morbidity or mortality (e.g., acute respiratory distress
or death). "Less serious" effects are those that are not expected to cause significant dysfunction or death,
or those whose significance to the organism is not entirely clear. ATSDR acknowledges that a
considerable amount of judgment may be required in establishing whether an endpoint should be

ENDRIN 10
2. HEALTH EFFECTS
classified as a NOAEL, "less serious" LOAEL, or "serious" LOAEL, and that in some cases, there will be
insufficient data to decide whether the effect is indicative of significant dysfunction. However, the
Agency has established guidelines and policies that are used to classify these endpoints. ATSDR believes
that there is sufficient merit in this approach to warrant an attempt at distinguishing between "less
serious" and "serious" effects. The distinction between "less serious" effects and "serious" effects is
considered to be important because it helps the users of the profiles to identify levels of exposure at which
major health effects start to appear. LOAELs or NOAELs should also help in determining whether or not
the effects vary with dose and/or duration, and place into perspective the possible significance of these
effects to human health.
A User's Guide has been provided at the end of this profile (see Appendix C). This guide should aid in
the interpretation of the tables and figures for LSEs and MRLs.
The health effects of endrin have been evaluated in 30 human studies and 63 animal studies. As
illustrated in Figure 2-1, most of the health effects data come from oral exposure studies in animals. For
the purposes of Figure 2-1, all occupational studies were classified as inhalation studies and all
population-based studies were classified as oral studies; however, it is acknowledged that humans were
likely exposed via multiple exposure routes in both occupational and environmental settings. For animal
data, oral studies are available for the majority of health effect categories and all exposure duration
categories. The inhalation and dermal animal databases are limited to three studies each, evaluating
limited endpoints. The most examined endpoints were neurological, death, hepatic, renal, and body
weight effects. Unless otherwise noted, the administered compound in animal studies was endrin; endrin
aldehyde or endrin ketone were only administered in three acute oral studies. The available human
studies were predominantly focused on neurological effects and cancer, with more recent studies focusing
on potential endocrine, reproductive, and developmental effects.
The human and animal studies suggest that the neurological and hepatic systems are the most sensitive
targets of endrin toxicity; other potential targets include the endocrine system, kidney, heart, and
developing organism.
• Neurological effects: Numerous case reports of convulsions following acute, high-level

exposure have been reported in workers who manufacture endrin and in cases of human oral
poisoning. Convulsions and other signs of overt neurotoxicity have also been observed in
numerous animal studies at or just below lethal exposure levels.

ENDRIN 11
2. HEALTH EFFECTS
• Hepatic effects: An occupational survey of workers who manufacture endrin (and other
organochlorine pesticides) reported occasional, transient changes in serum hepatic enzymes in
workers. Hepatic damage has also been observed in numerous animal studies at oral doses
associated with neurological effects.
• Endocrine effects: Data for this endpoint are limited. Human cross-sectional studies have
reported mixed and conflicting findings regarding potential associations between endrin exposure
and thyroid hormone levels. One chronic study in mice reported thyroid hyperplasia.
• Renal effects: No human data are available. Several oral studies reported renal effects;
however, observed effects were generally nonspecific (e.g., diffuse degeneration) and were
attributed to widespread systemic effects at lethal exposure levels. A few studies reported effects
at nonlethal doses, including increased kidney weight, cloudy swelling, and moderate tubular
necrosis.
• Cardiac and respiratory effects: Limited data from human studies do not indicate that the
cardiac and respiratory systems are sensitive targets of endrin toxicity. A few oral animal studies
reported cardiac and respiratory effects; however, these effects were generally nonspecific (e.g.,
increased weight, hemorrhage) and were attributed to widespread systemic effects at or near
lethal exposure levels.
• Developmental effects: Available human data are inadequate to determine if endrin exposure is
associated with birth outcomes or male reproductive development; however, one study reported
an association between endrin exposure and cord blood thyroid hormone levels. Teratogenic and
fetotoxic effects have been reported in gestational oral exposure studies in laboratory animals at
doses associated with maternal toxicity and death. These developmental effects are assumed to
be secondary to maternal toxicity. One study reported altered locomotor activity in rat and
hamster offspring following maternal exposure; effects in hamsters were only observed at
maternally toxic doses.

ENDRIN 12
2. HEALTH EFFECTS
Figure 2-1. Overview of the Number of Studies Examining Endrin Health Effects
Most studies examined the potential hepatic and neurological effects of endrin
Fewer studies evaluated health effects in humans than animals (counts represent studies examining endpoint)
*Includes studies discussed in Chapter 2. A total of 93 studies (including those finding no effect) have examined toxicity; most animal studies examined multiple
endpoints. All occupational studies were classified as inhalation studies and all population-based studies were classified as oral studies to avoid double counting
these studies; however, it is acknowledged that humans were likely exposed via multiple exposure routes in both occupational and environmental settings.

ENDRIN 13
2. HEALTH EFFECTS
Table 2-1. Health Effects in Humans Exposed to Endrin—Epidemiological Studies
Reference and study population Exposure Outcomes

Occupational studies
Ditraglia et al. 1981 Exposure levels not reported; exposure expected to Observed death (SMR; 95% CI)
Cohort study be primarily via inhalation, with potential for dermal
United States and oral exposure All causes:
Plant 2: 24/305 (66; 42–98)
Exposure group: All workers had been employed for ≥6 months Plant 3: 173/1155 (84; 72–98)
Plant 2: 305 workers from
heptachlor/endrin manufacturing Systems with significant increases in nonmalignant
plant disease:
Plant 3: 1,155 workers from Nonmalignant respiratory system disease
aldrin/dieldrin/endrin manufacturing Plant 2: 0/305
plant Plant 3: 22/1155 (212; 133–320)*
(Plants 1 and 4 did not
manufacture endrin) All malignant neoplasms:
Plant 2: 6/305 (91; 33–198)
Referent group: None (SMRs Plant 3: 31/1155 (82; 56–116)
calculated using general population
statistics) Specific cancers with nonsignificant increases:
Esophageal cancer
Plant 2: 0/305
Plant 3: 2/1155 (235; 26–850)
Rectal cancer
Plant 2: 0/305
Plant 3: 3/1155 (242; 49–707)
Liver cancer
Plant 2: 0/305
Plant 3: 3/1155 (242; 49–707)
Lymphatic and hematopoietic system cancer

Plant 2: 0/305
Plant 3: 6/1155 (147; 54–319)

ENDRIN 14
2. HEALTH EFFECTS

Hoogendam et al. 1962, 1965 Exposure levels not reported; exposure expected to Health effects noted during 9-year monitoring period:
Occupational health survey be primarily via inhalation, with potential for dermal
Netherlands and oral exposure 17 cases of convulsions with recovery within 1–
3 days; confirmed with abnormal EEGs
Exposure group: 592 workers Neurological cases had been employed for 3 days – (predominantly bilateral synchronous theta waves,
employed in an aldrin/dieldrin/ 4.5 years and liver cases had been employed for 1– and synchronous spike and wave complexes), which
endrin manufacturing plants 9 years; all observed symptoms expected to be due generally returned to normal within 0.5–1 month after
between 1956 and 1965 to acute, high exposures (potentially without removal from exposure
protective equipment)
Referent group: None 7 cases of abnormal liver function: 3 workers with
increased thymol turbidity, 1 worker with increased
AST, and 4 workers with increased ALT; all test
values returned to normal at subsequent evaluations
Piccoli et al. 2016 Exposure expected to be primarily via inhalation, with Adjusteda regression coefficients between serum
Cross-sectional study potential for dermal and oral exposure endrin levels and serum thyroid hormone levels
Brazil Total T3: 0.97 (0.94–0.99)*
Serum endrin levels detected >LOQ in 30.6% of Free T4: 0.98 (0.94–1.02)
Study population: 120 male and workers TSH: 0.99 (0.86–1.14)
155 female agricultural workers Median: <LOQ
95%: 179.7 ng/g
>50% had been agricultural workers for >25 years,

>40% had handled pesticides for >20 years
Ribbens 1985 Exposure levels not reported; exposure expected to Observed total mortality: 25
Cohort study be primarily via inhalation, with potential for dermal Expected total mortality: 38
Netherlands and oral exposure
Observed cancer mortality: 9
Exposure group: 232 previously Mean years exposed (range): 11 (4–27) Expected cancer mortality: 12
exposed workers in aldrin/dieldrin/ Mean years since exposed (range): 24 (4–29) Cancer SMR (95% CI): 0.75 (0.25–1.25)
endrin/telodrin manufacturing plant
Referent group: None (expected

mortality calculated using general
population statistics)

ENDRIN 15
2. HEALTH EFFECTS

Versteeg and Jager 1973 Exposure levels not reported; exposure expected to Mortality was limited to one accidental death
Cohort study be primarily via inhalation, with potential for dermal (automobile accident); there were no cases of
Netherlands and oral exposure malignant disease, hepatic disease, or epileptiform
convulsions
Exposure group: 52 former workers Mean years exposed (range): 6.6 (4.0–12.3)
in aldrin/dieldrin/endrin/telodrin Mean years since exposed (range): 7.4 (4.5–16)
manufacturing plant
Referent group: None

General population studies
Bapayeva et al. 2016 Route(s) of exposure unknown, but most likely Endrin levels were significantly elevated in exposure
Cohort study primarily oral via diet group compared with referents; lindane, dieldrin, and
South Kazakhstan DDT levels were also significantly elevated
Mean serum endrin levels±SD
Exposure group: 48 adolescent Exposure group: 37.57±0.9 mg/L Regression coefficient (R2) between reproductive
females (age 10–17 years) living in Referent group: 4.85±0.69 mg/L hormone levels and serum endrin (exposure and
cotton-growing rural regions referent groups combined)
FSH: -0.82705
Referent group: 40 adolescent Estradiol: -0.82705
females (age 10–17 years) living in
non-cotton-growing rural regions Significant changes in several parameters indicated
delayed physical and sexual development in female
adolescents exposed to endrin, lindane, dieldrin, and
DDT (endrin-specific analysis not conducted for these
parameters)
Altered parameters included decreased height, body

weight, chest circumference, external pelvic
measurement, and delayed development of
secondary sexual characteristics

ENDRIN 16
2. HEALTH EFFECTS

El Morsi et al. 2012 Route(s) of exposure unknown, may have occurred in Serum endrin levels were significantly elevated in
Case-control study utero, via diet, or via contact with contaminated cases versus controls
Egypt house dust, carpets, chemically treated gardens, or
pets treated with insecticides Odds ratio (95%) of having type 1 diabetes if endrin
Cases: 36 boys and 39 girls with was detected >LOQ in serum
type 1 diabetes (mean age Serum endrin levels were detected >LOQ in 10.7% of Unadjusted: 1.52 (1.32,1.75)*
6.01 years) cases and 0% of controls
Controls: 16 healthy boys and Median (minimum–maximum) endrin values:

19 healthy girls (mean age Cases: 0.90 (0.88–0.96) ng/mL
6.1 years) Controls: <LOQ
Fernandez et al. 2007 Route(s) of exposure unknown, but most likely Placental endrin levels were not elevated in cases
Case-control study primarily oral via diet compared with controls
Granada
Placental endrin levels were detected >LOQ in
Cases: 48 mother-son pairs, 22 cases (46%) and 48 controls (42%)
diagnosed with cryptorchidism
and/or hypospadias at birth Mean±SD (range) placental endrin levels (ng/g lipid)
Cases: 5.0±4.8 (3.0–19.47)
Controls: 114 mother-son pairs, no Controls: 7.4±11.9 (3.0–67.0)
malformations
Freire et al. 2011 Route(s) of exposure unknown, but most likely Odds ratio (95% CI) of having elevated TSHb in cord
Cross-sectional study primarily oral via diet blood (≥5 mU/L) if endrin was detected >LOQ in
Granada placenta
Placental endrin levels detected >LOQ in Unadjusted: 2.32 (1.18, 4.55)*
Study population: 220 mother-son 75 placental samples Adjustedc: 2.05 (1.01, 4.18)*
pairs (from a larger cohort of GM (95% CI): 2.53 (2.12, 3.01) ng/g placenta
700 mother-son pairs in the INMA- Association (β, 95% CI) between ln-transformed
Granada male birth cohort, born placental endrin levels and ln-transformed cord
between 2000 and 2002) thyroid hormones
Unadjusted: 0.08 (-0.10, 0.25)
Adjustedc: 0.03 (-0.15, 0.20)

ENDRIN 17
2. HEALTH EFFECTS

Freire et al. 2012 Primarily exposed via dermal contact and ingestion of Adjustedd regression coefficients (95% CI) between
Cross-sectional study contaminated soil, water, and locally produced food serum endrin levels and serum thyroid hormone
Brazil levels by quintile
Serum endrin levels detected >LOQ in 88.1% of Total T3
Study population: 193 children children Q1: referent
(<15 years old) from a rural area Median (20th–80th %): 1.49 (0.28, 3.56) ng/mL Q2: -0.80 (-13.3, 11.7)
(Cidade dos Meninos) with heavy Q3: -2.08 (-14.2, 10.0)
pesticide contaminations; mean Q4: 2.28 (-10.0, 14.6)
age 6.5 years (range 5 months– Q5 13.3 (1.15, 25.4)
14 years) p-trend: 0.03
Free T4
Q1: referent
Q2: -0.02 (-0.11, 0.07)
Q3: 0.03 (-0.06, 0.11)
Q4: 0.02 (-0.06,0.11)
Q5 0.02 (-0.07, 0.10)
p-trend: 0.42
TSH
Q1: referent
Q2: 0.33 (-0.10, 0.75)
Q3: 0.05 (-0.37, 0.46)
Q4: 0.17 (-0.25, 0.59)
Q5 0.38 (-0.03, 0.79)
p-trend: 0.19
Freire et al. 2013 Primarily exposed via dermal contact and ingestion of Adjustede association (β, 95% CI) between serum
Cross-sectional study contaminated soil, water, and locally produced food endrin levels and serum thyroid hormone levels
Brazil Total T3
Exposure duration: Men: -0.40 (-1.75, 0.95)
Study population: 303 men and Since birth: 82 men, 89 women Women: 0.62 (-1.39, 2.61)
305 women from a rural area Since childhood (<14 years old): 75 men,
(Cidade dos Meninos) with heavy 57 women Free T4
pesticide contaminations; mean Since adulthood (≥15 years old): 147 men, Men: -0.002 (-0.01, 0.01)
age 39 years 159 women Women: 0.01 (-0.004, 0.03)

ENDRIN 18
2. HEALTH EFFECTS
Serum endrin levels detected >LOQ in 87.4% of men TSH

and 87.1% of women Men: -0.03 (-0.07, 0.02)
Women: -0.02 (-0.09, 0.05)
Median (25th–75th %) serum endrin levels:
Men: 0.63 (0.24, 1.48) ng/mL When stratified by exposure duration, the study
Women: 0.58 (0.25,1.51) ng/mL authors reported that a positive relationship was
observed between serum endrin levels and serum T4
and TSH in women who were born in Cidade dos
Meninos; however, data were not provided and
statistical significance of findings were not discussed
Freire et al. 2014 Primarily exposed via dermal contact and ingestion of Adjustedf association (β, 95% CI) between serum
Cross-sectional study contaminated soil, water, and locally produced food endrin levels and serum reproductive hormone levels
Brazil
Exposure duration: Men
Study population: 304 men and Since birth: 82 men, 88 women Testosterone: -0.01 (-0.03,0.007)
300 women from a rural area Since childhood (<14 years old): 75 men,
(Cidade dos Meninos) with heavy 57 women Premenopausal women
pesticide contaminations; mean Since adulthood (≥15 years old): 147 men, Estradiol: 0.007 (-0.08, 0.09)
age 39 years 155 women Progesterone: -0.05 (-0.19,0.08)
Prolactin: 0.00 (-0.07, 0.07)
Serum endrin levels detected >LOQ in 87.4% of men, LH: -0.04 (-0.13, 0.06)
87.9% of premenopausal women, and 87.0% of FSH: -0.04 (-0.13, 0.06)
peri-/postmenopausal women
Peri-/postmenopausal women
Median (25th-75th%) serum endrin levels: Estradiol: 0.008 (-0.05, 0.07)
Men: 0.63 (0.24, 1.48) ng/mL Progesterone: 0.007 (-0.05, 0.07)
Premenopausal women: 0.59 (0.27,1.57) ng/mL Prolactin: 0.02 (-0.10, 0.14)
Postmenopausal women: 0.54 (0.23, 1.38) ng/mL LH: -0.09 (-0.19, 0.01)
FSH: -0.05 (-0.13, 0.03)

ENDRIN 19
2. HEALTH EFFECTS

Henriques-Hernandez et al. 2014 Route(s) of exposure unknown, but most likely Odds ratio (95% CI) of having hypertension (systolic
Cross-sectional study primarily oral via diet blood pressure >140 mmHg, diastolic blood pressure
Canary Islands >90 mmHg, or antihypertensive medication) if endrin
Serum endrin levels detected >LOQ in 291 samples was detected >LOQ in blood
Study population: 191 males, Median (25th–75th%): 0.23 (0.00–0.49) µg/L Unadjusted: 1.077 (0.980–1.184); p=0.124
237 females; aged 18.1–77.3 years
Samra and Selim 2009 Route(s) of exposure unknown, but most likely Mean maternal and cord serum endrin levels were
Cross-sectional study primarily oral via diet significantly elevated (p<0.001) in preterm deliveries,
Egypt compared with full term (note that several other
Mean±SD maternal serum endrin levels organochlorine pesticides were also significantly
123 mother-child pairs (including Preterm: 0.223±0.516 mic/L elevated; e.g., heptachlor, dieldrin, DDT)
43 women with preterm deliveries Full-term: 0.003±0.014 mic/L
and 80 women with full-term Correlation coefficients between maternal serum
deliveries) Mean±SD cord blood serum endrin levels endrin levels and birth outcomes (preterm and full-
Preterm: 0.208±0.497mic/L term births combined)
Full-term: 0.002±0.010 mic/L Gestational age: -0.332 (p=0.000)
Weight: -0.345 (p=0.000)
Length: -0.298 (p=0.001)
Head circumference: -0.322 (p=0.000)
Correlation coefficients between cord serum endrin

levels and birth outcomes (preterm and full-term
births combined)
Gestational age: -0.332 (p=0.000)
Weight: -0.345 (p=0.001)
Length: -0.298 (p=0.001)
Head circumference: -0.322 (p=0.000)
Note: Despite p-values indicating significance, the

study authors did not conclude that correlations
between endrin and birth outcomes were significant;
the rationale for this discrepancy is unclear

ENDRIN 20
2. HEALTH EFFECTS

Rowley et al. 1987 Cause for outbreak unverified, but expected to be Patients presented with CNS symptoms; 19/194 died
Case-series report food contamination
Pakistan
Study population:194 cases of

acute poisoning
Curley et al. 1970; Weeks 1967 Dietary exposure estimates ranged from 48 to Patients presented with convulsions, loss of
Case series report 1,807 ppm (contaminated flour contained 2,153– consciousness, headache, nausea, and vomiting;
Saudi Arabia 3,367 ppm endrin) 26/874 patients died within 12 hours
Study population: 874 people Recovery was rapid in survivors

hospitalized after acute exposure
to endrin-contaminated flour
aAdjusted for sex, age, BMI, current smoking status, and alcohol intake.
bDefined as “moderately elevated neonatal concentration” by the World Health Organization.
cAdjusted for maternal age, gestational age, alcohol consumption and cigarette smoking during pregnancy, parity, birth weight, maternal education, and placental
lipid concentration.
dAdjusted for age (continuous), sex, triglycerides, and cholesterol.
eAdjusted for age, ethnicity, and years of residence in Cidade dos Meninos.
fAdjusted for age, ethnicity, years of residence in Cidade dos Meninos, BMI, and smoking.
* = statistically significant (p<0.05), as reported by the study authors; ALT = alanine transferase; AST = aspartate transaminase; BMI = body mass index;
CNS = central nervous system; CI = confidence interval; EEG = electroencephalogram; FSH = follicle-stimulating hormone; GM = geometric mean;
INMA = Infancia y Medio Ambiente; LH = luteinizing hormone; LOQ = level of quantitation; Q = quintile; SD = standard deviation; SMR = standardized mortality
ratio; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid stimulating hormone

ENDRIN 21
2. HEALTH EFFECTS
Table 2-2. Levels of Significant Exposure to Endrin – Inhalation
Less
Species serious Serious
Figure (strain) Exposure Doses Parameters NOAEL LOAEL LOAEL
keya No./group parameters (ppm) monitored Endpoint (ppm) (ppm) (ppm) Effect
INTERMEDIATE EXPOSURE
1 Mouse 150 days 0.36 LE Death 0.36 1/3 died
(NS) 5 days/week
3 NS 7 hours/day
Treon et al. 1955
2 Rabbit 165 days 0.36 LE Death 0.36 2/4 died
(NS) 5 days/week
4 NS 7 hours/day
Treon et al. 1955
aThe number corresponds to entries in Figure 2-2.
LE = lethality; LOAEL = lowest-observed-adverse-effect level; NOAEL = no-observed-adverse-effect level; NS = not specified

ENDRIN 22
2. HEALTH EFFECTS
Figure 2-2. Levels of Significant Exposure to Endrin – Inhalation

Intermediate (15–364 days)

ENDRIN 23
2. HEALTH EFFECTS
Table 2-3. Levels of Significant Exposure to Endrin/Endrin Aldehyde/Endrin Ketone – Oral
Less
keya No./group parameters (mg/kg/day) monitored Endpoint (mg/kg/day) (mg/kg/day) (mg/kg/day) Effect
ACUTE EXPOSURE
1 Monkey Once Not reported LE Death 3 LD50
(NS) (GO)
2B
Endrin
Treon et al. 1955
2 Rat 1–2 days 0, 8.2 BC, BI, BW, Bd wt 8.2
(Sprague- (F) HP, OF, Hepatic 8.2 48–82% increase in hepatic serum
Dawley) OW enzymes (ALP, AST, ALT, serum
4F isocitrate dehydrogenase) and 27–
35% increase in cholesterol);
vacuolization; fatty infiltration
Other 8.2 41–51% decrease in serum
noncancer glucose
Endrin
Ali and Shakoori 1993
3 Rat Once 0, 3, 4.5, 6 OW, BI Hepatic 3 Increased relative liver weight
(Sprague- (GO)
Dawley)
4F
Endrin
Bagchi et al. 1992a
4 Rat Once 0, 1.5, 3, OW, BI Hepatic 3 11% increase in relative liver
(Sprague- (GO) 4.5, 6 weight relative to low-dose group
Dawley) (control values not reported)
4F
Endrin
Bagchi et al. 1992b

ENDRIN 24
2. HEALTH EFFECTS
Less
5 Rat Once 0, 3, 4.5, 6 OW, BI Hepatic 3 9% increase in relative liver weight
(Sprague- (GO)
Dawley)
4F
Endrin
Bagchi et al. 1992c
6 Rat Once Not reported LE, CS Death 5.6 M LD50
(Carworth (G) 5.3 F
Farm E)
4–8 M, 4–
8F
Endrin
Bedford et al. 1975a
7 Rat 8 days, 0, 1–3 BC, BI, OW, Cardio 1
(Hotlzman every 2– UR Hepatic 1
albino) 3 days
Renal 1
10 M (GO)
Neuro 1
Endrin
Coleman et al. 1968 [TWA dose = 1 mg/kg/day]
8 Rat Once Not reported LE Death 17.8 M LD50
(Sherman) (GO) 7.5 F
90 M, 50 F
Endrin
Gaines 1960, 1969
9 Rat 9d 0, 0.1, 0.5, MX, DX, FX, Death 2 2/25 died on GDs 13 and 14
(Sherman) GDs 6–15 2.0 TG, CS, Bd wt 0.5 2 Decreased maternal weight gain
25 F (G) BW, LE (12% of control)
Develop 0.5 2 Delayed ossification
Endrin
Goldenthal et al. 1978a [Note: vehicle was methocel]

ENDRIN 25
2. HEALTH EFFECTS
Less
10 Rat Once 0, 4 HP, BI Hepatic 4 Moderate focal necrosis, fatty
(Sprague- (GO) degeneration, inflammation, and
Dawley) cell regeneration; 1.9-fold increase
4F in lipid peroxidation
Renal 4 Moderate tubular necrosis, hyaline
and red cell casts; 3.3-fold
increase in lipid peroxidation
Endrin
Hassan et al. 1991
11 Rat Once 0, 4.5 BI, EA Hepatic 4.5 14.5% increase in mitochondrial
(Sprague- (GO) lipid peroxidation at 6 hours; 28%
Dawley) increase at 12 hours
4F
Endrin
Hassoun et al. 1993
12 Rat 14 days 0, 0.075, LE, OW, Bd wt 0.15 0.3 38% decrease in maternal body
(CD) GDs 7–20 0.15, 0.3, BW, CS, weight gain
15–32 F (GO) 0.45 OF, DX, TG Hepatic 0.45
Develop 0.45
Endrin
Kavlock et al. 1981
13 Rat 14 days 0, 0.5, 1, 2, LE, BW, Death 0.5 3/5 died; 100% mortality at higher
(CD) (GO) 4 BH, CS doses
5–9 F Bd wt 0.5 94% decrease in body weight gain
in survivors
Neuro 0.5b 4 Depressed locomotor activity at
≥0.5 mg/kg; convulsions in 2/6 rats
at 4 mg/kg
Endrin
Kavlock et al. 1981 [Range-finding study; neurological assessment conducted 2–4 hours after initial dose]

ENDRIN 26
2. HEALTH EFFECTS
Less
14 Rat Once 0, 25 BC, BI, OW Cardio 25 15% increase in heart weight
(Hotlzman (GO) Hepatic 25 27% increase in liver weight
albino)
Renal 25 9% increase in kidney weight
10–12 M
Neuro 25 Convulsions
Endrin
Lawrence et al. 1968
15 Rat 3 days 0, 0.5, 1, 5 CS, BI Neuro 1 5 Tremors and convulsions
(Sprague- (GO)
Dawley)
4M
Endrin
Mehrotra et al. 1989
16 Rat Once 0, 0.5, 1, 2, BI, BW, OW Bd wt 4
(Sprague- (GO) 4 Hepatic 4 No change in liver weight
Dawley)
4F Renal 4 No change in kidney weight
Endrin
Numan et al. 1990a
17 Rat Once 0, 8 LE Death 8 100% mortality
(Sprague- (GO)
Dawley)
10 F
Endrin
Numan et al. 1990b
18 Rat Once 20–80 LE Death 40 LD50
(Sprague- (GO)
Dawley)
Endrin
Speck and Maaske 1958

ENDRIN 27
2. HEALTH EFFECTS
Less
19 Rat Once Not reported LE Death 7.3 F LD50
(Carworth) (GO) 43.4 M
10 M, 10 F
Endrin
Treon et al. 1955 [Rats exposed at 6 months of age]
20 Rat Once Not reported LE Death 16.8 F LD50
(Carworth) (GO) 28.8 M
10 M, 10 F
Endrin
Treon et al. 1955 [Rats exposed at PND 29, 30, or 31]
21 Mouse Once 0, 4 HP, BI Hepatic 4 Moderate focal necrosis and
(Swiss (GO) inflammation; 1.8-fold increase in
Webster) lipid peroxidation
4F Renal 4 Moderate tubular necrosis; 1.7-fold
increase in lipid peroxidation
Endrin
Hassan et al. 1991
22 Mouse Once 0, 4.5, 6 BW, FX, LE, Death 6 25% maternal death
(C57BL/6J) GD 12 MX, TG Bd wt 6
5–8 F (GO)
Develop 4.5 6 10% decrease in fetal weight, 13%
decrease in fetal thymus weight,
and 14% decrease in placental
weight at 4.5 mg/kg;
28.9% fetal death/resorption, 28%
decrease in fetal weight, 17%
decrease in fetal thymus weight,
and increased percent of
fetuses/litter with hydronephrosis
at 6 mg/kg
Endrin
Hassoun and Stohs 1996b

ENDRIN 28
2. HEALTH EFFECTS
Less
23 Mouse Once 0, 4.5, 6 BW, FX, LE, Death 6 25% maternal death
(DBA/2J) GD 12 MX, TG Bd wt 6
5–8 F (GO)
Develop 4.5 6–13% decrease in fetal weight at
≥4.5 mg/kg; 20% decrease in
placental weight at 6 mg/kg
Endrin
Hassoun and Stohs 1996b
24 Mouse 11 days 0, 0.5, 1.0, LE, OW, Death 1.5 4/20 died at 1.5 mg/kg/day;
(CD-1) GDs 7–17 1.5, 2.0 BW, CS, 18/20 died at 2.0 mg/kg/day
20–40 F (GO) OF, DX, TG Bd wt 0.5 1 24% decrease in maternal body
weight gain
Hepatic 0.5 1 10% increase in relative liver
weight
Develop 0.5 1 Delayed ossification, decrease in
number of caudal vertebrae,
altered development of renal
pelvis, decreased fetal body
weight
Endrin
Kavlock et al. 1981
25 Mouse 11 days 0, 0.5, 1.5, LE, BW, Death 4.5 100% mortality
(CD-1) (GO) 4.5 BH, CS Bd wt 0.5 1.5 43% decrease in body weight gain
7–8 F
Neuro 0.5 1.5 38–46% decrease in locomotor
activity on days 1 and 3
Endrin
Kavlock et al. 1981 [Range-finding study; neurological assessment conducted 2–4 hours after 1st, 3rd, and 10th doses]

ENDRIN 29
2. HEALTH EFFECTS
Less
26 Mouse Once 0, 7, 9 LE, BW, Death 7 3/21 died
(CD-1) GD 8 CS, HP, GN Develop 7 Increased incidence of
21–40 F (GO) exencephaly, fused ribs, and
supernumerary ribs
Endrin
Kavlock et al. 1985
27 Mouse Once 0, 2.5 FX, MX, DX, Develop 2.5 2.7% increase in open eye; 2.2%
(CD-1) GD 9 TG increase in cleft palate
10 F (GO)
Endrin
Ottolenghi et al. 1974
28 Guinea pig Once 0, 4 HP, BI Hepatic 4 Moderate focal necrosis and
(NS) (GO) inflammation; 1.3-fold increase in
4F lipid peroxidation
Renal 4 Cloudy swelling and narrowing of
tubular lumen
Endrin
Hassan et al. 1991
29 Guinea pig Once Not reported LE Death 16 F LD50
(NS) (GO) 36 M
2 M, 2 F
Endrin
Treon et al. 1955

ENDRIN 30
2. HEALTH EFFECTS
Less
30 Hamster 10 days 0, 0.75, 1.5, LE, OW, Death 1.5 37% of dams died
(Golden GDs 5–14 2.5, 3.5 BW, CS, Bd wt 0.75 1.5 19 times more weight loss than
Syrian) (GO) FX, MX, TG, controls
20–63 F DX
Hepatic 3.5
Develop 0.75 1.5 2-fold increase in fetal death; 30%
decrease in fetal weight, skeletal
and visceral abnormalities
Endrin
Chernoff et al. 1979a
31 Hamster Once 0, 0.5, 1.5, LE, OW, Neuro 7.5 10 1/30 animals displayed
(Golden GD 8 5, 7.5, 10 BW, CS, convulsions
Syrian) (GO) FX, MX, TG, Develop 1.5 5.0 Increased incidence (5/7) of
18–87 F DX meningoencephaloceles
Endrin
32 Hamster Once Not reported LE, OW, Death 18.6 LD50
(Golden (GO) BW, CS,
Syrian) FX, MX, TG,
NS F DX
Endrin
33 Hamster 10 days 0, 0.1, 0.75, MX, DX, FX, Develop 2.5
(Golden GDs 4–13 2.5 TG, CS,
Syrian) (G) BW, LE
28 F
Endrin
Goldenthal et al. 1978b [Vehicle was methocel]

ENDRIN 31
2. HEALTH EFFECTS
Less
34 Hamster 10 days 0, 0.75, 1.5 LE, BX, FX, Death 1.5 57% of dams died
(Golden GDs 5–14 OF, DX, CS Neuro 0.75 Hypoactivity
Syrian) (GO)
10–63 F Develop 0.75 1.5 Altered habituation in locomotor
testing on PNDs 15–125
Endrin
Gray et al. 1981
35 Hamster Once 0, 4 HP, BI Hepatic 4 Moderate necrosis and
(NS) (GO) inflammation, 1.3-fold increase in
4F lipid peroxidation
Renal 4 Moderate tubular necrosis, hyaline
and calcium containing casts, lipid
peroxidation
Endrin
Hassan et al. 1991
36 Hamster Once 0, 5 FX, DX, TG Develop 5 Increased incidence of dead and
(Golden GD 7, 8, or resorbed fetuses, increased
Syrian) 9 incidence of cleft palate and fused
8F (GO) ribs, decreased fetal weight;
increased incidence of open eye
and webbed feet after exposure on
GD 8 only
Endrin
Ottolenghi et al. 1974
37 Rabbit Once Not reported LE, CS, GN, Death 7–10 LD50
(NS) (GO) HP, BW,
4F OW BC,
Endrin
Treon et al. 1955

ENDRIN 32
2. HEALTH EFFECTS
Less
38 Rat 79 days 0, 0.005, BW, DX, Repro 0.1
(Long- (F) 0.05, 0.1 FX, GN, HP, Develop 0.1
Evans) OW
10 M/10 F
(F0)
Endrin
Eisenlord et al. 1968 [3-generation study]
39 Rat 28 days 0, 0.075, LE, BX, FX, Develop 0.075 0.15 Altered habituation in locomotor
(CD) GD 7– 0.15, 0.3 OF, DX, CS testing in offspring on PND 16 and
5–21 F PND 15 20
(GO)
Endrin
Gray et al. 1981
40 Rat 10 weeks Males: 2, 5 LE, BW, Death 5M 3/3 males died
(Carworth) 5 day/week Females: 1, CS, GN 2F 1/3 females died
3 M, 3 F (GO) 2
Endrin
Treon et al. 1955 [Rats 6 months of age at start of exposure]
41 Rat 10 weeks 1, 2 LE, BW, Death 2F 1/2 females died
(Carworth) 5 days/week CS, GN
3 M, 2–3 F (GO)
Endrin
Treon et al. 1955 [Rats PND 29 at start of exposure]
42 Rat 15 days 0, 0.25, 0.5 BC, OF Hepatic 0.25 Altered hepatobiliary function; no
(Sprague- (F) change in serum ALT or AST
Dawley)
6 M, 6 F
Endrin
Young and Mehendale 1986

ENDRIN 33
2. HEALTH EFFECTS
Less
43 Rat 15 days 0, 0.5 BC, OF Hepatic 0.5 10-fold increase in serum ALT and
(Sprague- (F) 5-fold increase in serum AST; no
Dawley) change in hepatobiliary function
6M
Endrin aldehyde
44 Rat 15 days 0, 0.25 BC, OF Hepatic 0.25 8-fold increase in serum ALT, no
(Sprague- (F) change in hepatobiliary function
Dawley)
6M
Endrin ketone
45 Mouse 120 days 0, 0.65 LE, OF Death 0.65 Deaths in 33/101 breeding pairs
(CFW (F) Repro 0.65 5% reduction in litter size
Swiss)
101 M,
101 F
Endrin
Good and Ware 1969 [1-generation study]
46 Dog Up to 0.18, 0.24, LE, CS, GN, Death 0.24 M Death in 1/1 after 47 days; 1/2
(Beagle) 9.9 months 0.38, 0.46, HP, BW, died at 0.38 and 0.46 mg/kg/day;
1–4 B 6 days/week 0.62, 0.65, OW, BC 100% mortality at higher doses
(F) 1.71, 3.25
Endrin
Treon et al. 1955 [Doses above represent the midpoint of the reported range for each dose group]
47 Rabbit 10 weeks 1 LE Death 1 4/5 rabbits died
(NS) 5 days/week
5F (GO)
Endrin
Treon et al. 1955

ENDRIN 34
2. HEALTH EFFECTS
Less
CHRONIC EXPOSURE
48 Rat 17.6– 0, 0.1, 0.29, GN, HP, LE, Bd wt 0.56
(Osborne 20.8 months 0.56 BW Resp 0.1 Congestion, focal hemorrhage
Mendel) (F)
50–100 M, Hepatic 0.1 Cloudy swelling of centrilobular
50–100 F cells
Renal 0.1 Cloudy swelling of tubule epithelial
cells
Neuro 0.1 Convulsions and tremors
Cancer No neoplastic lesions in liver,
kidney, or lungs
Endrin
Deichmann et al. 1970
49 Rat 80 weeks Males: 0, LE, CS, HP, Bd wt 0.25
(Osborne- (F) 0.13, 0.25 GN, UR, Resp 0.13 Shortness of breath, epistaxis
Mendel) Females: 0, BW
10–50 M, 0.15, 0.3 Cardio 0.25
10–50 F Gastro 0.13 Diarrhea
Hepatic 0.25
Renal 0.13 Discolored urine
Dermal 0.13 Dermatitis, alopecia
Endocr 0.13 Thyroid hyperplasia and pituitary
cysts
Neuro 0.25
Cancer No exposure-related neoplasms
Endrin
NCI 1978
50 Rat 2 years 0, 0.08, LE, CS, GN, Death 2.1 F Increased mortality
(Carworth) (F) 0.42, 2.1, HP, BW, 4.2 M
20 M, 20 F 4.2, 8.4 OW, BC Bd wt 0.42 M 2.1 M >10% reduction in weight gain

ENDRIN 35
2. HEALTH EFFECTS
Less
Hepatic 0.08 M 0.42 M >10% increase in relative liver
0.42 F 2.1 F weight in males at
≥0.42 mg/kg/day and in females at
≥2.1 mg/kg/day; diffuse
degeneration of the liver in
animals that died
Renal 0.42 2.1 Diffuse degeneration of kidneys in
animals that died
Endocr 0.42 2.1 Diffuse degeneration of adrenals
in animals that died
Neuro 0.42 2.1 4.2 Diffuse degeneration of the brain
in animals that died; convulsions
and hypersensitivity at
≥4.2 mg/kg/day
Endrin
Treon et al. 1955
51 Mouse 80 weeks Males: 0, LE, CS, HP, Bd wt 0.42
(B6C3F1) (F) 0.21, 0.42 GN, UR, Resp 0.42
10–60 M, Females: 0, BW
10–60 F 0.33, 0.65 Cardio 0.42
Gastro 0.21 Abdominal distension
Hepatic 0.42
Renal 0.42
Dermal 0.21 Hair loss
Endocr 0.42
Neuro 0.21 M Hyperexcitability
0.33 F
Cancer No exposure-related neoplasms
Endrin
NCI 1978

ENDRIN 36
2. HEALTH EFFECTS
Less
52 Dog 2 years 0, 0.0025, BW, FI, BC, Bd wt 0.1
(Beagle) (F) 0.0125, HE, HP, Resp 0.1
3 M, 3 F 0.025, 0.05, OW, CS
0.1 Cardio 0.1
Gastro 0.1
Hemato 0.1
Musc/skel 0.1
Hepatic 0.025c F 0.05 F Hepatic cell vacuolation
0.05 M 0.1 M
Renal 0.1
Dermal 0.1
Ocular 0.1
Endocr 0.1
Immuno 0.1
Neuro 0.025c F 0.05 F Convulsions
0.05 M 0.1 M
Endrin
Kettering 1969
53 Dog 64– 0, 0.003, BW, FI, CS, Hemato 0.059
(Beagle) 156 weeks 0.014, OW, HP, Hepatic 0.059
3F (F) 0.027, GN, BC,
0.059 MX, UR Renal 0.059
Neuro 0.059 Seizures
Endrin
Kettering 1971

ENDRIN 37
2. HEALTH EFFECTS
Less
54 Dog 16.4– 0, 0.08, LE, CS, GN, Bd wt 0.19
(Beagle) 18.7 months 0.19 HP, BW, Resp 0.19
2–4 B 6 days/week OW, BC
(F) Cardio 0.08 0.19 25% increase in relative heart
weight
Hemato 0.19
Hepatic 0.19
Renal 0.08 0.19 24% increase in relative kidney
weight
Immuno 0.19
Neuro 0.19
Endrin
Treon et al. 1955 [Doses above represent the midpoint dose of the reported range for each dose group]
aThe number corresponds to entries in Figure 2-3; differences in levels of health effects and cancer effects between male and females are not indicated in
Figure 2-3. Where such differences exist, only the levels of effect for the most sensitive sex are presented.
bUsed to derive a provisional acute oral minimal risk level (MRL) of 0.0006 mg/kg/day; BMDL
1SD of 0.06 mg/kg divided by an uncertainty factor of 100 (10 for
extrapolation from animals to humans and 10 for human variability). The provisional acute oral MRL was adopted as the provisional intermediate oral MRL.
cUsed to derive and chronic oral MRL of 0.0003 mg/kg/day; dose divided by an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for
human variability).
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; B = both male(s) and female(s); BC = serum (blood) chemistry;
Bd Wt or BW = body weight; BH = behavioral; BI = biochemical changes; BMD = benchmark dose; BMDL = 95% lower confidence limit on the BMD (subscripts
denote benchmark response: i.e., 1SD = exposure concentration associated with 1 standard deviation change in outcome); Cardio = cardiovascular; CS = clinical
signs; Develop = developmental; DX = developmental toxicity; EA = enzyme activity; Endocr = endocrine; (F) = food; F = female(s); FI = food intake; FX = fetal
toxicity; (G) = gavage; (GO) = gavage in oil; Gastro = gastrointestinal; GD = gestational day; GN = gross necropsy; HE = hematology; Hemato = hematological;
HP = histopathology; LD50 = lethal dose, 50% kill; LE = lethality; LOAEL = lowest-observed-adverse-effect level; M = male(s); MX = maternal toxicity;
Neuro = neurological; NOAEL = no-observed-adverse-effect level; NS = not specified; OF = organ function; OW = organ weight; PND = postnatal day;
Repro = reproductive; Resp = respiratory; TG = teratogenicity; TWA = time-weighted average; UR = urinalysis

ENDRIN 38
2. HEALTH EFFECTS
Figure 2-3. Levels of Significant Exposure to Endrin/Endrin Aldehyde/Endrin Ketone – Oral

Acute (≤14 days)

ENDRIN 39
2. HEALTH EFFECTS

Acute (≤14 days)

ENDRIN 40
2. HEALTH EFFECTS

Intermediate (15-364 days)

ENDRIN 41
2. HEALTH EFFECTS

Chronic (≥365 days)

ENDRIN 42
2. HEALTH EFFECTS

Chronic (≥365 days)

ENDRIN 43
2. HEALTH EFFECTS
Table 2-4. Levels of Significant Exposure to Endrin – Dermal
Less
(strain) Exposure Doses Parameters NOAEL LOAEL LOAEL
No./group parameters (mg/kg/day) monitored Endpoint (mg/kg/day) (mg/kg/day) (mg/kg/day) Effect
ACUTE EXPOSURE
Rat Once Not reported LE Death 15 LD50
(Sherman)
NS F
Gaines 1960 [A total of 50 rats were used in study, number per group not reported]
Rat Once Not reported LE Death 18 LD50
(Sherman)
NS M
Gaines 1969 [A total of 40 rats were used in study, number per group not reported]
Rabbit 24 hours 60, 94, 125, LE, GN, HP Death 94 1/3 died
(NS) 160, 250– Dermal 3,600
3–8 F 3,600
Treon et al. 1955
Rabbit 25– 27–44 LE, GN, HP Death 27–44 1/4 died
(NS) 45 exposures Dermal 27–44
4F 5 days/week
2 hours/day
Treon et al. 1955 [Abraded skin]
Rabbit 19– 20–42, 67– LE, GN, HP Death 20–42 1/3 died at low dose; 3/3 died at
(NS) 70 exposures 91 high dose
3F 5 days/week Dermal 67–91
2 hours/day
Treon et al. 1955 [Intact skin]
F = female(s); LD50 = lethal dose, 50% kill; GN = gross necropsy; HP = histopathology; LE = lethality; LOAEL = lowest-observed-adverse-effect level; M = male(s);
NOAEL = no-observed-adverse-effect level; NS = not specified

ENDRIN 44
2. HEALTH EFFECTS
2.2 DEATH
Deaths have rarely been associated with occupational exposure to endrin. Retrospective cohort studies
have reported lower than expected overall mortality in workers manufacturing endrin (along with related
chemicals) compared to the general population, likely due to the healthy worker effect (Ditraglia et al.
1981; Ribbens 1985). One facility that manufactured aldrin, endrin, and dieldrin reported a significant
excess of death due to nonmalignant respiratory system disease, but similar effects were not observed in
another facility that manufactured heptachlor and endrin (Ditraglia et al. 1981; see Table 2-1). These
studies are limited by small cohort size and/or multiple chemical exposures. Human reports of high
occupational exposure have not reported deaths, even at exposure levels high enough to cause tonic-
clonic contractions and seizures (Hoogendam et al. 1962, 1965).
Human deaths have occurred following community-wide poisoning events involving acute exposure to
endrin via ingestion. In 1967, 26/ 874 hospitalized people died in Saudi Arabia following exposure to
endrin-contaminated flour containing 2,153–3,367 ppm endrin (Weeks 1967). Estimated concentrations
of endrin in bread eaten by victims ranged from 48 to 1,807 ppm (Curley et al. 1970). A similar outbreak
of endrin poisoning in 1984 resulted in 19/194 patient deaths in Pakistan; however, the source of the
contamination was not identified (assumed to be a contaminated food item) (Rowley et al. 1987). In both
cases, severe central nervous system toxicity preceded death.
Case studies also report death following acute ingestion of endrin. A 49-year old man died 11 days after
intentional ingestion of 12 g of endrin dissolved in aromatic hydrocarbons (~171 mg/kg); death was
preceded by convulsions (Runhaar et al. 1985). Eleven other cases of endrin ingestion resulted in death
within 1–6 hours after exposure (Tewari and Sharma 1978). In cases where endrin ingestion occurred
with milk or alcohol, death occurred more rapidly (within 1–2 hours), presumably as the result of
enhanced absorption that increased toxicity. An elderly senile woman died 7 hours after ingesting an
unknown quantity of liquid pesticide containing endrin; tissue concentrations ranged from 0.467 to
13.3 mg/kg, and the amount of endrin adsorbed onto activated charcoal (administered as a treatment) was
66 mg (Moriya and Hashimoto 1999).
Studies involving laboratory animals have reported death following inhalation exposure. A cat exposed
twice for 1 hour to 417 ppm endrin as a spray of 1.5% aqueous solution died within 24 hours (Ressang et
al. 1959). In another inhalation study, six species of animals were exposed to endrin vapor at 0.36 ppm
for 7 hours/day, 5 days/week for 150–185 days (Treon et al. 1955). Two of four rabbits died after 26 and

ENDRIN 45
2. HEALTH EFFECTS
90 exposures, and one of three mice died after 22 exposures. The cat, two guinea pigs, two hamsters, and
three rats survived. Additional groups of one to two mice survived 18–64 exposures over 3–13 weeks
(5 days/week; 7 hours/day), and additional three rabbits survived 12 exposures over 16 days (7 hours/day)
(Treon et al. 1955). Diffuse degenerative changes were observed in kidneys, livers, and brains in all
animals that died, except in the mouse where effects on the brain were not observed.
Endrin is also lethal to animals when sufficiently high doses are administered by gavage or in the diet.
Reported oral LD50 values (the dose that has been calculated to cause death in 50% of the experimental
animal population) ranged from 3 mg/kg in monkeys (Treon et al. 1955), 5.3–43.4 mg/kg in adult rats
(Bedford et al. 1975a; Gaines 1960, 1969; Speck and Maaske 1958; Treon et al. 1955), 16.8–28.8 mg/kg
in young rats approximately 4–5 weeks old (Treon et al. 1955), 16–36 mg/kg in guinea pigs (Treon et al.
1955), 18.6 mg/kg in hamsters (Chernoff et al. 1979a), and 7–10 mg/kg in rabbits (Treon et al. 1955).
Phillips et al. (1962) reported an acute oral LD50 of >500 mg/kg for endrin aldehyde in male mice, but did
not provide experimental details. Other single-exposure studies observed mortality in 100% of rats at
8 mg/kg dose (Numan et al. 1990b), a cat that was exposed to 3 mg/kg/day for 3 days (Ressang et al.
1959), a cat that was exposed once to 6 mg/kg (Ressang et al. 1959), and 7/8 hunting dogs that accidently
ingested an unknown quantity in endrin-containing bait (Quick et al. 1989). Single or repeated doses of
endrin to pregnant dams during gestation also resulted in maternal lethality at doses as low as
0.5 mg/kg/day in rats (Goldenthal et al. 1978a; Kavlock et al. 1981), 1.5 mg/kg/day in mice (Hassoun and
Stohs 1996b; Kavlock et al. 1981, 1985), or 1.5 mg/kg/day in hamsters (Chernoff et al. 1979a; Gray et al.
1981). Longer-duration studies have reported increased mortality in rats at chronic dietary doses
≥2.1 mg/kg/day (Treon et al. 1955), in mice administered 0.42 mg/kg of endrin in feed for 120 days
(Good and Ware 1969), and in dogs exposed to doses ≥0.24 mg/kg/day for ≥47 days (Treon et al. 1955).
Dermal studies reported LD50 values of 18 mg/kg in male rats and 15 mg/kg in female rats for endrin in
xylene (Gaines 1960, 1969). In cats (one cat/group), topical application of 75 mg/kg in a 0.5%
formulation resulted in death 22 days later and topical application of 150 mg/kg in a 2.5% formulation
resulted in the death within 48 hours; however, application of 75 mg/kg in a 2.5% formulation did not
result in death or toxic signs in another cat (Ressang et al. 1959). In rabbits, dermal exposure to 94 mg/kg
for 24 hours resulted in death in 1/3 animals; 2/3 died at 60 mg/kg, and mortality was 100% at
≥250 mg/kg (Treon et al. 1955). When rabbits were exposed for longer durations, 1/4 rabbits died
following 25 applications of endrin at doses ranging from 27 to 44 mg/kg/day on abraded skin (the
remaining three rabbits survived 45 exposures), 1/3 rabbits died following 40 applications of endrin at
doses ranging from 20 to 42 mg/kg/day on intact skin (the remaining two rabbits survived

ENDRIN 46
2. HEALTH EFFECTS
70 applications), and 3/3 rabbits died following 19–25 applications of endrin at doses ranging from 67 to
91 mg/kg on intact skin (Treon et al. 1955). Regardless of exposure duration, convulsions preceded death
and animals that died showed diffuse degenerative lesions of the liver, kidney, and brain.
2.3 BODY WEIGHT
No studies were located regarding body weight effects in humans following exposure to endrin.
Laboratory studies have observed body weight effects in multiple species following oral endrin exposure.
Studies involving pregnant animals reported significant decreases in body weight gain in maternal rats at
≥0.3 mg/kg/day, mice at ≥1 mg/kg/day, and hamsters at ≥1.5 mg/kg/day for 9–11 days during gestation
(Chernoff et al. 1979a; Goldenthal 1978a; Kavlock et al. 1981). Nonpregnant animals did not experience
body weight effects following single oral exposures up to 8.2 mg/kg in rats (Ali and Shakoori 1993;
Numan et al. 1900a) or 6 mg/kg in mice (Hassoun and Stohs 1996a). In an older study, dogs became
emaciated prior to death following exposure to dietary doses ≥0.24 mg/kg/day for up to 9.9 months;
according to the authors, the dogs “did not grow normally” at the nonlethal dose of approximately
0.18 mg/kg/day (Treon et al. 1955). However, the inadequate data reporting did not clearly define an
effect level in this study. Chronic studies in dogs did not observe body weight effects following dietary
doses up to 0.19 mg/kg/day (Kettering 1969; Treon et al. 1955). Chronic rodent dietary studies reported
significant decreases in body weight gain in male rats exposed to doses ≥2.1 mg/kg/day, but not
≤0.56 mg/kg/day; female rats showed no body weight effects at doses up to 5 mg/kg/day, and doses up to
0.42 mg/kg/day did not affect body weights of male or female mice (Deichmann et al. 1970; NCI 1978;
Treon et al. 1955).
2.4 RESPIRATORY
Information regarding potential respiratory effects in humans following endrin exposure is extremely
limited. In a retrospective cohort study (see Table 2-1 for details), the number of deaths due to
nonmalignant respiratory diseases (e.g., pneumonia) was increased in workers employed at a plant that
manufactured aldrin, dieldrin, and endrin, compared with the rate in the general population (Ditraglia et
al. 1981). However, Ditraglia et al. (1981) did not observe an excess of death from nonmalignant
respiratory disease in another plant that manufactured endrin and heptachlor. The only additional
information on endrin’s potential to cause respiratory disease or dysfunction in humans comes from a
case report of pulmonary edema in a patient that attempted suicide by drinking an endrin formulation
(Runhaar et al. 1985). However, the study authors attributed pulmonary edema to chemical pneumonitis

ENDRIN 47
2. HEALTH EFFECTS
resulting from aspiration of aromatic hydrocarbons contained in the ingested formulation, since
hydrocarbon-induced chemical pneumonitis is a well-established clinical entity.
Information regarding potential respiratory effects in laboratory animals following inhalation exposure is
limited to a single, inadequately designed lethality study in multiple species. The authors reported
granulomatous pneumonitis in two rabbits that survived intermittent exposure to 0.36 ppm of endrin
vapors over 165 days (7 hours/day, 5 days/week); however, the study did not include control animals, so
it is unclear if this finding is exposure-related (Treon et al. 1955). The study authors did not report
pneumonitis in one cat, two guinea pigs, two hamsters, three rats, or two mice that survived similar
exposure for up to 185 days, but the limited data reporting, small animal number, and lack of controls
limits the usefulness of this study. Therefore, no NOAEL/LOAEL determinations for respiratory effects
were included in the LSE for this study.
There are also limited data regarding respiratory effects in animals following oral exposure to endrin.
Severe congestion and serofibrinous exudate were observed in the lungs of five hunting dogs that died
after acute exposure via ingestion of an unknown quantity of endrin-containing bait (Quick et al. 1989).
In an intermediate-duration study in dogs, the study authors noted respiratory distress, pulmonary
hyperplasia and edema in all dogs that died following exposure to dietary doses ≥0.24 mg/kg/day for up
to 9.9 months (Treon et al. 1955). However, the study did not provide a clearly defined effect level due to
inadequate data reporting. Moreover, the dogs were observed regurgitating their food and may have
aspirated endrin-contaminated material. In chronic oral studies, rats exposed to dietary doses
≥0.1 mg/kg/day exhibited shortness of breath and focal hemorrhage and congestion of the lungs at
necropsy (Deichmann et al. 1970; NCI 1978). No adverse respiratory effects were observed in similarly
exposed mice at dietary doses up to 0.42 mg/kg/day (NCI 1978) or dogs at dietary doses up to
0.1 mg/kg/day (Kettering 1969).
2.5 CARDIOVASCULAR
Two human studies contained limited information on the potential effects of endrin exposure on
cardiovascular function and health (see Table 2-1 for details). A population-based study in the Canary
Islands found no association between hypertension and serum endrin levels (Henriques-Hernandez et al.
2014). In a retrospective cohort study, workers employed at plants that manufactured endrin (and other
chemicals) for at least 6 months did not have an increased risk of death due to circulatory system disease

ENDRIN 48
2. HEALTH EFFECTS
compared with the general population (Ditraglia et al. 1981). One plant reported a significantly decreased
risk of death due to circulatory system disease, likely due to the healthy worker effect.
Limited reports of cardiovascular toxicity of orally administered endrin in animals were located. An
acute rat study reported a 15% increase in heart weight following a single gavage exposure to 25 mg/kg
(Lawrence et al. 1968); however, this finding is difficult to interpret in the absence of histological
examination. No change in heart weight was observed in rats exposed to 1 mg/kg/day for 8 days via
gavage (Coleman et al. 1968). At intermediate durations, diffuse degeneration changes occurred in the
hearts of dogs who died following exposure to dietary doses ≥0.24 mg/kg/day for up to 9.9 months (Treon
et al. 1955). However, data reporting was inadequate to clearly define an effect level for this finding.
Chronic rodent studies did not observe cardiovascular lesions in rats at doses up to 0.25 mg/kg/day or in
mice at doses up to 0.42 mg/kg/day (NCI 1978). A chronic dog study noted a 25% increase in relative
heart weight without cardiac lesions following exposure to an approximate dietary dose of
0.19 mg/kg/day for up to 18.7 months (Treon et al. 1955). A second chronic dog study did not observe
any exposure-related changes in lung weight or histology at dietary doses up to 0.1 mg/kg/day for 2 years
(Kettering 1969).
2.6 GASTROINTESTINAL
A report of nausea and vomiting in people who consumed endrin-contaminated taquitos provides the only
available human data on potential gastrointestinal effects (Waller et al. 1992).
In chronic dietary studies, rats exhibited diarrhea at doses ≥0.13 mg/kg/day and mice had abdominal
distension at ≥0.21 mg/kg/day; however, rats did not develop gastrointestinal lesions at doses up to
0.25 mg/kg/day or mice at doses up to 0.42 mg/kg/day (NCI 1978). Treon et al. (1955) noted that dogs
regurgitated food containing endrin at dietary levels of ≥0.24 mg/kg/day (Treon et al. 1955). No
gastrointestinal lesions were observed in dogs exposed to dietary levels up to 0.1 mg/kg/day for 2 years
(Kettering 1969).
2.7 HEMATOLOGICAL
No studies were located regarding hematological effects in humans following exposure to endrin.
The only available animal data on hematological effects are from three dog studies that found no
hematological effects following chronic oral exposure. The peripheral blood of male and female dogs

ENDRIN 49
2. HEALTH EFFECTS
given endrin in their diet at doses up to 0.19 mg/kg/day for periods of 16.4–18.7 months did not show
changes in the relative numbers or types of formed elements (Treon et al. 1955). Similarly, no
hematological changes were observed in dogs administered doses up to 0.059 mg/kg/day for 64–
156 weeks or 0.1 mg/kg/day for 2 years (Kettering 1969, 1971).
2.8 MUSCULOSKELETAL
No studies were located regarding musculoskeletal effects in humans following exposure to endrin. The
only animal study evaluating musculoskeletal effects reported a lack of exposure-related histological
changes in skeletal muscle or bone in dogs given endrin in their diet at doses up to 0.1 mg/kg/day for
2 years (Kettering 1969).
2.9 HEPATIC
Two occupational reports assessed hepatic effects in humans exposed to chemical mixtures that included
endrin. Seven of 592 workers manufacturing aldrin/dieldrin/endrin had abnormal liver function tests, as
shown by three cases of increased thymol turbidity, increased serum aspartate transaminase (AST) in one
worker, and increased serum alanine aminotransferase (ALT) in four workers (Hoogendam et al. 1965).
Exposure to other compounds was not controlled, and serum values returned to normal during continued
exposure. No cases of hepatic disease were reported in 52 former workers from an
aldrin/dieldrin/endrin/telodrin manufacturing plant (Versteeg and Jager 1973).
In the only available inhalation study evaluating hepatic effects in animals, diffuse degenerative changes
were observed in the livers of rabbits and mice exposed over 6 months at a lethal endrin concentration of
0.36 ppm (Treon et al. 1955). The authors did not provide details of the liver pathology.
Oral studies in animals consistently report histopathological changes in the liver (e.g., degeneration,
necrosis, vacuolization, hypertrophy, lipid peroxidation) following single- or repeat-dose exposure to
endrin. There is inconsistent evidence for elevated liver weight and changes in hepatic serum chemistry
parameters.
Three studies have reported histopathological changes in the liver following acute oral exposures in
multiple species. An LD50 study reported diffuse hepatic degeneration in multiple species at lethal doses
(Treon et al. 1955). Rats, mice, and guinea pigs administered 4 mg/kg endrin and sacrificed 24 hours
later showed moderate hepatic necrosis, fatty degeneration (rats only), and inflammation; histological

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examination found lipofuscin deposits in hepatocytes and Kupffer cells (Hassan et al. 1991). Similar
changes were observed in control and endrin-treated hamsters; however, the hepatic effects were more
severe in the treated animals, and only livers from treated animals had lipofuscin pigment deposits
associated with lipid peroxidation (Hassan et al. 1991). Hepatic cell hypertrophy, dilation of sinusoidal
spaces, zonal disorganization/degeneration, vacuolization, and fatty infiltration were also observed in the
livers of rats exposed to dietary endrin at doses of 8.2 mg/kg/day for 2 days (Ali and Shakoori 1993).
Congestion and serofibrinous exudate were observed in the livers of dogs that died apparently following
ingestion of endrin-containing bait (Quick et al. 1989).
Two intermediate-duration oral studies in dogs and rats also observed histopathological changes in the
liver; however, inadequate data reporting in both studies precluded identification of a clearly defined
effect level. Speck and Maaske (1958) reported spotty livers with zones of basophilic cells around the
central and portal veins in rats exposed to endrin for 3–7 months; however, the report does not clearly
identify the dose at which these effects occurred (administered doses were 0.8, 1.7, and 3.5 mg/kg/day).
Treon et al. (1955) reported diffuse degeneration changes in the livers of dogs that died following
exposure to dietary doses ≥0.24 mg/kg/day for up to 9.9 months; in some cases, fatty vacuolation
occurred (number not specified).
In chronic-duration studies, histopathological findings in the liver have been inconsistent between studies
and species. The livers of Osborne-Mendel rats exposed to dietary levels ≥0.1 mg/kg/day for 17.6–
20.8 months showed minor histologic changes (cloudy swelling of centrilobular cells) (Deichman et al.
1970); however, NCI (1978) did not report any exposure-related nonneoplastic hepatic lesions in
Osborne-Mendel rats exposed to dietary levels up to 0.25 mg/kg/day for 80 weeks. In another chronic
study, diffuse degeneration occurred in the livers of Carworth rats that died following dietary exposure to
doses as low as 2.1 mg/kg/day for up to 2 years; lesions were not observed at nonlethal doses
≤0.42 mg/kg/day (Treon et al. 1955). No significant increase in nonneoplastic hepatic lesions was
observed in B6C3F1 mice exposed to dietary endrin levels up to 0.42 mg/kg/day for 80 weeks (NCI
1978). In chronic dog studies, Kettering (1969) reported slight vacuolization of hepatic cells in dogs
following exposure to dietary doses ≥0.05 mg/kg/day for 2 years (Kettering 1969), but Treon et al. (1955)
did not observe hepatic lesions in dogs following exposure to dietary doses up to 0.19 mg/kg/day for
16.4–18.7 months. Additionally, a 1-generation study found no hepatic lesions in female dogs exposed to
doses up to 0.059 mg/kg/day for 64–156 weeks in (Kettering 1971).

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A series of acute studies reported time- and dose-related increases in relative liver weights (9–30%) in
rats administered a single oral dose of 3–6 mg/kg and sacrificed at intervals over 3 days, compared with
the lowest dose of 1.5 mg/kg; organ weight data were not reported for concurrent control groups in these
studies (Bagchi et al. 1992a, 1992b, 1992c). A significant 27% increase in absolute liver weight occurred
in rats exposed once to 25 mg/kg (Lawrence et al. 1968); body and relative liver weights were not
reported. In contrast, no significant changes in liver weight were noted for rats 24 hours after a single
oral administration of 4 mg/kg (Numan et al. 1990a), dietary exposure to 8.2 mg/kg/day for 1–2 days (Ali
and Shakoori 1993), or gavage administration of 1–3 mg/kg every 2–3 days for 8 days (total dose
8 mg/kg) (Coleman et al. 1968). Studies in pregnant animals reported increases in maternal relative liver
weight ≥10% in mice administered ≥1 mg/kg/day of endrin for 11 days during gestation (Kavlock et al.
1981), but not in hamsters and rats at doses up to 3.5 or 0.45 mg/kg/day, respectively (Chernoff et al.
1979a; Kavlock et al. 1981).
In chronic-duration studies, relative liver weights increased by >10% in male rats exposed to doses
≥0.42 mg/kg/day and female rats exposed to doses ≥2.1 mg/kg/day for up to 2 years (Treon et al. 1955).
In dogs, no significant or biologically relevant liver weight changes were observed at doses up to
approximately 3.25 mg/kg/day for up to 9.9 months (Treon et al. 1955), 0.19 mg/kg/day for up to
18.7 months (Treon et al. 1955), 0.059 mg/kg/day for 64–156 weeks (Ketttering 1971), or 0.1 mg/kg/day
for 2 years (Kettering 1969).
Significant alterations in liver serum enzymes occurred in Sprague-Dawley rats following dietary
exposure to approximately 8.2 mg/kg/day for 1–2 days (Ali and Shakoori 1993). After 24 and 48 hours,
endrin exposure caused a significant 48–69% increase in alkaline phosphatase, a 82–97% increase in
AST, a 55–71% increase in ALT, and a 65% increase in isocitrate dehydrogenase, relative to controls.
Serum cholesterol also significantly increased by 27 and 35% at 24 and 48 hours, respectively (Ali and
Shakoori 1993). A 15-day dietary exposure experiment evaluating liver function in rats after exposure to
endrin, endrin aldehyde, or endrin ketone reported 10- and 5-fold elevations in serum ALT and AST,
respectively, following exposure to 0.5 mg/kg/day endrin aldehyde. Serum ALT also increased 8-fold
following exposure to 0.25 mg/kg/day endrin ketone; neither serum ALT or AST significantly changed
following exposure to endrin doses up to 0.5 mg/kg/day (Young and Mehendale 1986). However, endrin-
treated animals experienced alterations in hepatobiliary function, as measured by phenolphthalein
glucuronide or bile flow, (decreased in males, increased in females), but not animals treated with endrin
aldehyde or endrin ketone (Young and Mehendale 1986).

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Rabbits fatally poisoned by an acute dermal endrin dose ≥94 mg/kg body weight had centrilobular
degeneration of the liver (Treon et al. 1955). The study did not provide details regarding the
histopathology of the lesions and only tested a small number of animals. Rabbits surviving multiple skin
applications exhibited severe fatty degeneration of the liver.
Mechanisms of Hepatotoxicity. Administration of endrin to animals has been associated with hepatic
histopathology, including the presence of lipofuscin pigment (Hassan et al. 1991). One laboratory studied
the ability of endrin to elicit hepatic lipid peroxidation and associated cell injury. Administration of
single doses of endrin to rats was associated with increased lipid peroxidation, decreased membrane
fluidity, and deoxyribonucleic acid (DNA) damage (single strand breaks) in hepatocytes (Bagchi et al.
1995a,1995b, 1992a, 1993a, 1993c, 2000, 2002; Hassoun et al. 1993). The authors suggested that
membrane alterations and DNA damage may result from the enhanced formation of free radical or
reactive oxygen species. These reactive species could lead to altered cell proliferation and differentiation,
potentially through activation of the protein kinase C (PKC) pathway (Bagchi et al. 1997). Endrin caused
dose-related increases in lipid peroxidation in rats resulting in breakdown of polyunsaturated fatty acids
as evidenced by the urinary excretion of the lipid metabolites formaldehyde, acetaldehyde,
malondialdehyde, and acetone (Bagchi et al. 1992b). Induction of microsomal cytochrome P450 has also
been observed following intraperitoneal injections of endrin (Khan et al. 1998). As discussed in Section
2.20 (Mechanisms of Toxicity), general mechanisms of toxicity that may contribute to observed hepatic
toxicity include glutathione depletion and alterations in metal homeostasis. Pretreatment with various
antioxidants (vitamin E succinate, ellagic acid, lazaroid U74389F) ameliorated endrin-related lethality,
histopathologic damage, lipid peroxidation, DNA damage, glutathione depletion, alterations in iron
homeostasis, and excretion of lipid metabolites (Bagchi et al. 1992c, 1993c, 1995b; Hassan et al. 1991;
Numan et al. 1990a, 1990b).
In studies with dioxin-responsive and -nonresponsive strains of mice, there was no clear evidence for
involvement of the Ah receptor in endrin-induced lipid peroxidative effects in liver (Bagchi et al. 1993d).
Endrin is also not likely to exert hepatotoxicity via peroxisome proliferator-activated receptors (PPARs)
because it was not an agonist for mouse PPARɑ or PPARγ in an in vitro reporter gene assay (Takeuchi et
al. 2006). However, endrin was a human pregnane X receptor (hPXR) agonist in an in vitro reporter gene
assay, resulting in induction of CYP3A4 and CYP2B6 in hepatocytes (Lemaire et al. 2004). Together,
PXR and the constitutive androstane receptor (CAR) can mediate hepatotoxicity via alterations in
metabolism and hepatic proliferations (Hernandez et al. 2009). No information on whether or not endrin
can induce CAR was available (Hernandez et al. 2009).

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Macrophages from endrin-exposed rats or mice showed an increase in the concentration of nitric oxide
(Akubue and Stohs 1992; Bagchi et al. 1993d) and increased chemiluminescence and production of
superoxide anion (Bagchi et al. 1993a). Based on these results and those described above for hepatic
microsomal and mitochondrial alterations, it appears that multiple sources of reactive oxygen species may
be involved in endrin-mediated cell damage.
2.10 RENAL
No studies were located regarding renal effects in humans following exposure to endrin.
One inhalation study found diffuse degenerative changes in the kidneys of two rabbits and one mouse that
died following exposure to 0.36 ppm of endrin (Treon et al. 1955). The study did not provide further
details of the kidney pathology.
Kidney damage has been reported in multiple species following acute oral exposure. Consistent with
inhalation data, diffuse degenerative changes were also observed in the kidneys of multiple species at
lethal oral doses in LD50 studies; no further information was reported (Treon et al. 1955). In other acute
oral studies, moderate tubular necrosis and congestion, inflammation, and interstitial edema were
observed in rats and mice sacrificed 24 hours after a single oral exposure to 4 mg/kg (Hassan et al. 1991).
These effects without inflammation were also observed in similarly exposed hamsters, and cloudy
swelling of cells and narrowing of tubular lumina were observed in similarly exposed guinea pigs (Hassan
et al. 1991). Severe congestion and serofibrinous exudate were observed in the kidneys of dogs that died
following apparent ingestion of endrin-containing bait (Quick et al. 1989). Among acute studies that only
evaluated kidney weight, one reported a 9% increase in rats following a single gavage exposure to
25 mg/kg (Lawrence et al. 1968), but another found no effect after a single exposure to 4 mg/kg (Numan
et al. 1990a) or to 1–3 mg/kg/day for 8 days (dosed every 2–3 days; time-weighted average [TWA] dose
= 1 mg/kg/day) (Coleman et al. 1968).
Kidney damage was also seen in longer-duration oral studies, but generally only at concentrations
resulting in increased mortality. An older study observed diffuse degeneration changes in the kidneys of
dogs that died following exposure to dietary doses ≥0.24 mg/kg/day for up to 9.9 months (Treon et al.
1955). However, data reporting was inadequate to clearly define an effect level. These lesions were not
observed at nonlethal concentrations up to approximately 0.19 mg/kg/day for up to 2 years (Treon et al.

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1955), but did cause a 24% increase in relative kidney weight (Treon et al. 1955). Exposure to
0.08 mg/kg/day had no effect on kidney weight. No changes in kidney weight or histology were observed
in dogs exposed to dietary concentrations up to 0.1 mg/kg/day for 2 years (Kettering 1969). Diffuse
degeneration of the kidney also occurred in rats that died following dietary exposure to doses as low as
2.1 mg/kg/day for 2 years; nonlethal doses ≤0.42 mg/kg/day did not result in kidney lesions (Treon et al.
1955). In addition, cloudy swelling of tubule epithelial cells occurred in rats chronically exposed to
nonlethal doses ranging from 0.1 to 0.56 mg/kg/day (Deichmann et al. 1970). An NCI (1978) bioassay of
rats and mice did not observe any pathological changes in the kidney at dietary doses up to 0.25 and
0.42 mg/kg/day, respective; however, discolored urine occurred in rats administered >0.13 mg/kg/day.
Dermal exposure to lethal doses of endrin once or for an intermediate duration resulted in diffuse
degenerative changes of the kidney in rabbits (Treon et al. 1955).
2.11 DERMAL
No studies were located regarding dermal effects in humans following exposure to endrin.
Chronic administration of endrin in feed resulted in alopecia in mice (0.21 mg/kg/day) and both dermatitis
and alopecia in rats (0.13 mg/kg/day) at the lowest tested doses (NCI 1978). In dogs, no changes in skin
histology were observed at dietary doses up to 0.1 mg/kg/day for 2 years (Kettering 1969). No damage to
the skin at the site of application was observed in rabbits exposed to a single or repeated dermal
application of dry endrin (Treon et al. 1955).
2.12 OCULAR
No studies were located regarding ocular effects in humans following exposure to endrin. The only
animal study evaluating ocular effects reported a lack of exposure-related histological changes in the eyes
of dogs given endrin in their diet at doses up to 0.1 mg/kg/day for 2 years (Kettering 1969).
2.13 ENDOCRINE
Several epidemiological studies have examined the potential relationship between environmental endrin
exposure and thyroid hormone levels. In general, the studies observed only weak (if any) relationships,
and reported inconsistent findings between studies, sexes, and age groups (see Table 2-1 for more details).
In Brazilian agricultural workers, a weak, but statistically significant, association was observed between

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serum endrin levels and decreased serum total triiodothyronine (T3) levels; no association was observed
between serum endrin levels and serum thyroid stimulating hormone (TSH) or free thyroxine (T4) levels
(Piccoli et al. 2016). The predominant exposure route is expected to be inhalation; however, dermal and
oral exposure may have also occurred. In the general population, no significant associations were
observed between serum total T3, free T4, or TSH levels in adults living in a heavily contaminated rural
area in Brazil (Freire et al. 2013). When stratified by exposure duration, Freire et al. (2013) reported that
a positive relationship was observed between serum endrin levels and serum T4 and TSH in women who
were born in the area; however, data are not provided and statistical significance of findings were not
discussed. In contrast, children from the same area showed a significant increase in total T3 levels with
increasing serum endrin levels, but no associations were observed between serum endrin levels and serum
T4 or TSH (Freire et al. 2012). In infants, the risk of elevated cord blood TSH levels was increased
2-fold when endrin was detected in the placenta (Freire et al. 2011; see Section 2.17 Developmental for
more details). Exposure in these studies is most likely via dermal contact and ingestion of contaminated
soil, water, and locally produced food. A major limitation in all these studies is lack of adjustment for
measured serum levels of other pesticides.
El Morsi et al. (2012) provides limited evidence of a potential risk of type 1 diabetes in children with
endrin exposure. This case-control study in Egypt reported a significant increase in serum endrin levels
in children diagnosed with type 1 diabetes compared with healthy controls (see Table 2-1 for more
details). The risk of having type 1 diabetes was significantly increased by 1.5-fold with detectible serum
endrin levels. However, the study did not adjust for any confounders, including other detectible
pesticides. Exposure may have occurred in utero, via diet, or via contact with contaminated house dust,
carpets, chemically treated gardens, or pets treated with insecticides.
Data regarding potential endocrine effects in laboratory animals exposed to endrin are limited. In a
chronic dietary bioassay, thyroid hyperplasia and pituitary cysts were observed in rats at dietary doses
≥0.13 mg/kg/day, but not mice at doses up to 0.42 mg/kg/day (NCI 1978). In another chronic study in
rats, diffuse degeneration of the adrenal glands was observed in rats that died following dietary exposure
to doses as low as 2.1 mg/kg/day for 2 years; lesions were not observed at nonlethal doses
≤0.42 mg/kg/day (Treon et al. 1955). In dogs, no changes in thyroid, adrenal, pancreas, or pituitary
weight and/or histology were observed following dietary exposure to doses up to 0.1 mg/kg/day for
2 years (Kettering 1969).

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2.14 IMMUNOLOGICAL
No studies were located regarding immunological or lymphoreticular effects in humans after inhalation
exposure to endrin. An in vitro study of endrin effects on human lymphocyte mitogenic responses to
phytohemagglutinin and neutrophil chemotaxis was negative (Lee et al. 1979).
Immunological data in animals following exposure to endrin are limited to inconsistent alterations in
immune organ weight following oral exposure. Time- and dose-related increases in spleen-to-body
weight ratios were observed in rats administered a single oral dose of 1.5–6 mg/kg and sacrificed at
intervals over 3 days, while relative thymus weights were decreased (Bagchi et al. 1992b, 1992c). Organ
weight data were not reported for concurrent control groups in these studies. No changes in spleen weight
were observed in rats sacrificed 2 hours following a single exposure to 25 mg/kg; thymus weights were
not evaluated (Lawrence et al. 1968). In another acute rat study, increased absolute spleen weights were
observed in rats exposed to a total of 8 mg/kg over 8 days (dosed every 2–3 days); however, interpretation
of these data are difficult due to lack of body weight data despite reported “changes in eating habits”
(Coleman et al. 1968). Thymus weights were not evaluated by Coleman et al. (1968). In dogs, there were
no effects on spleen weight at dietary doses up to 0.19 mg/kg/day for 16.4–18.7 months (Treon et al.
1955) or dietary doses up to 0.1 mg/kg/day for 2 years (Kettering 1969). The adversity of the sporadic
organ weight findings is unclear due to inconsistency and lack of concurrent histopathological evaluation;
therefore, no NOAEL/LOAEL determinations were made for immune effects based on organ weight data.
The only study evaluating immune organ histology was Kettering (1969), which reported a lack of
exposure-related histopathological changes in spleen, thymus, mesenteric lymph nodes, and bone marrow
in dogs exposed to dietary endrin at doses up to 0.1 mg/kg/day. No studies evaluating immune function
were available.
Decreased thymic weight was reported in mouse fetuses following maternal exposure to ≥4.5 mg/kg/ on
gestation day (GD) 12 (Hassoun and Stohs 1996a, 1996b); see Section 2.17 (Developmental) for more
information.
2.15 NEUROLOGICAL
Studies in humans demonstrate that the nervous system is a primary target for acute endrin toxicity in the
occupational setting. Exposure in this setting is primarily due to inhalation, with potential for dermal and
oral exposure. An occupational health survey at a plant that manufactured aldrin, dieldrin, and endrin,
reported 17 acute cases of convulsions over a 9-year period (Hoogendam et al. 1962, 1965). The authors

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stated that acute, high exposures, often without proper protective gear, accounted for all the cases;
however, they did not report any exposure levels. After removal from exposure, seizures subsided, and
the patients made a complete recovery within 1–3 days. Abnormal electroencephalograms (EEGs) were
usually observed in endrin-poisoned workers, and sometimes occurred without any clinical symptoms.
Predominantly bilateral synchronous theta waves, and synchronous spike and wave complexes were seen
(Hoogendam et al. 1962). These are believed to be associated with brain stem injury. Abnormal EEGs
generally returned to normal within a period of 0.5–1 month after removal of the worker from exposure
(Hoogendam et al. 1965). Retrospective cohort studies evaluating long-term effects of occupational
organochlorine exposure (including endrin) in former workers reported no incidences of epileptiform
convulsions in the years following employment (Versteeg and Jager 1973), and did not observe excesses
in death due to neurological diseases (Ditraglia et al. 1981).
Poisoning episodes in humans show that the central nervous system is the primary target system of orally
administered endrin. Acute human poisonings by endrin-contaminated food caused symptoms of central
nervous system toxicity such as jerking of arms and legs, tonic-clonic contractions, convulsions, and
sudden collapse and death (Carbajal-Rodriquez et al. 1990; Coble et al. 1967; Curley et al. 1970; Davies
and Lewis 1956; Rowley et al. 1987; Waller et al. 1992; Weeks 1967). Convulsions were also reported in
a man who attempted suicide by drinking an endrin formulation (Runhaar et al. 1985).
In a severe case of poisoning in a 1-year-old child, severe convulsions, coma, decerebrate rigidity, and
permanent brain injury occurred after the child played in his room following application of an endrin-
containing pesticide (endrin content and other compounds present not available) (Jacobziner and Raybin
1959). The floors and walls of the boy’s room had endrin residue; therefore, the exposure was likely a
combination of dermal and oral (due to hand-to-mouth activities of young children).
Data regarding potential neurological effects in animals following inhalation exposure to endrin are
limited to reports of diffuse lesions in acute lethality studies. Degenerative lesions of the brain were
observed in two rabbits that died after exposure to 0.36 ppm for 165 days (5 days/week); these lesions
were not observed in a mouse that died after similar exposure (Treon et al. 1955). Seizures were not
observed prior to death. Ressang et al. (1959) also reported slight degenerative lesions of ganglion cells
in the brains of a cat exposed to a lethal concentration of endrin.
Neurological effects are commonly observed in animals following acute oral exposure to endrin. Diffuse
degenerative changes were observed in the brains of multiple species at lethal doses in LD50 studies; no

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further information was reported (Treon et al. 1955). Beagle dogs that had apparently ingested endrin-
containing bait exhibited tetanic convulsions (Quick et al. 1989). Death occurred within 45 minutes of
the onset of convulsions in five of eight dogs (and later for an additional two of eight dogs). Tremors and
convulsions were noted in rats administered acute doses ≥4 mg/kg (Gaines 1960; Kavlock et al. 1981;
Lawrence et al. 1968; Mehrotra et al. 1989; Speck and Maaske 1958), but not ≤3 mg/kg (Coleman et al.
1968; Kavlock et al. 1981; Mehrotra et al. 1989). Decreased activity levels were observed in pregnant
rats, mice, and hamsters administered endrin during gestation at doses as low as 0.5 mg/kg/day (Gray et
al. 1981; Kavlock et al. 1981). Altered neurodevelopment was observed in some rat and hamster
offspring (Gray et al. 1981); see Section 2.17 (Developmental) for more information.
Neurological effects were also observed in longer-duration oral studies. The most sensitive species
appears to be the dog, with convulsions observed at chronic doses ≥0.05 mg/kg/day (Kettering 1969,
1971). An intermediate-duration study observed various neurological effects (lethargy, tremors,
twitching, hyperirritability to stimuli, convulsions, tremors, and diffuse degenerative brain lesions) in
animals that died following exposure to dietary doses of approximately ≥0.24 mg/kg/day for up to
9.9 months; however, data reporting in this study is inadequate to define an effect level (Treon et al.
1955). Petechial hemorrhages and cerebral edema were observed in the brain of one dog having
convulsions at the time of death (Kettering 1969). In rats, Deichmann et al. (1970) reported convulsions
and tremors following chronic dietary exposure to ≥0.1 mg/kg/day; however, no clinical signs of
neurotoxicity or brain lesions were observed in rats in an NCI (1978) bioassay at dietary exposures up to
0.25 mg/kg/day. In another chronic study in rats, diffuse degeneration of the brain was observed in rats
that died following dietary exposure to doses as low as 2.1 mg/kg/day and convulsions and
hypersensitivity to stimuli were observed at lethal doses ≥4.2 mg/kg/day; these effects were not observed
at nonlethal doses ≤0.42 mg/kg/day (Treon et al. 1955). Speck and Maaske (1958) reported altered EEGs
and audiogenic convulsions (convulsions triggered by noise) in rats exposed to endrin for 3–7 months;
however, the report does not clearly indicate the dose(s) at which these effects occurred (administered
doses were 0.8, 1.7, and 3.5 mg/kg/day); due to inadequate reporting, this study was not included in the
LSE. Mice exhibited hyperexcitability following dietary doses of ≥0.21 mg/kg/day for up to 80 weeks;
however, no histologic changes in the brain were found (NCI 1978).
Convulsions, tremors, and/or twitching of the facial muscles were the chief signs of endrin intoxication in
rabbits and rats following dermal exposure (Gaines 1960; Treon et al. 1955). Diffuse degenerative
lesions of the brain were observed in rabbits that died (Treon et al. 1955).

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Mechanisms of Neurotoxicity. The mechanism by which endrin induces its neurotoxic effects has been
the subject of a number of research investigations. Based on experimental and clinical findings of
convulsions and seizures in humans and animals, and altered electrophysiologic activity in animals,
endrin appears to exert its neurotoxic effects at the level of the central nervous system. The 12.5-fold
greater toxicity of endrin when administered intracerebrally versus intraperitoneally to male mice
supports the brain being the primary target site for endrin (Bloomquist 1992).
Central nervous system function may be altered via changes in neurotransmitter systems, particularly the
inhibitory γ-aminobutyric acid (GABA) system. In vitro exposure of male rat brain preparations to endrin
induced noncompetitive inhibition of GABA-regulated chloride transport (Wafford et al. 1989) and
chloride current in patch clamp studies (Narahashi 1991). Other studies support the correlation between
inhibition of GABA-dependent chloride uptake and the acute intracerebral toxicity of endrin (Bloomquist
1992). The results of these studies support the hypothesis that endrin disrupts the GABAergic system,
which could explain observed hyperexcitability of the central nervous system and convulsions. No
evidence of alterations in the serotonergic system were observed following in vivo exposure in mice
(Miller and Fink 1973) or the dopaminergic system following in vitro exposure in PC6-3 cells (Allen et
al. 2013).
Alterations in calcium homeostasis could also contribute to neurotoxicity of endrin. Mehrotra and
coworkers (1989) observed that isolated fractions of brain and heart cells from rats orally administered
0.5–10 mg endrin/kg showed significant inhibition of Ca+2 pump activity and decreased levels of
calmodulin, indicating disruption of membrane Ca+2 transport mechanisms; exogenous addition of
calmodulin restored Ca+2-ATPase activity. In vitro exposure of rat brain synaptosomes and heart
sarcoplasmic reticuli decreased total and calmodulin-stimulated calcium ATPase activity with greater
inhibition in brain preparations (Mehrotra et al. 1989). However, endrin showed no inhibitory effects on
the calmodulin-sensitive calcium ATPase activity when incubated with human erythrocyte membranes
(Janik and Wolf 1992). In vitro exposure of rat brain synaptosomes to endrin had no effect on the
activities of adenylate cyclase or 3’,5’-cyclic phosphodiesterase, two enzymes associated with synaptic
cyclic AMP metabolism (Kodavanti et al. 1988).
Studies in one laboratory show that administration of single doses of endrin to rats was associated with
increased lipid peroxidation and DNA damage (single strand breaks) in brain tissue (Bagchi et al. 1995a,
1995b, 2000, 2002). DNA damage associated with generation of reactive oxygen species was also
observed in PC-12 neuroactive cells exposed to endrin in vitro (Bagchi et al. 1995a), and induction of

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protective heat shock (stress) proteins was observed (Bagchi et al. 1996). As discussed in Section 2.9
(Hepatic), these effects were also observed in hepatocytes. This pathway may represent a general
mechanism by which endrin exerts toxicity in various tissues, including tissues of the nervous system.
2.16 REPRODUCTIVE
A number of epidemiological studies have examined reproductive outcomes in the context of endrin use
in agricultural regions. However, the data are inadequate to determine the potential for endrin to cause
adverse reproductive effects.
An Egyptian case-control study found significantly elevated maternal and cord serum organochlorine
levels (including endrin) in 43 cases of premature delivery compared with 80 full-term deliveries (Samra
and Selim 2009). However, when the authors combined cases and controls for analysis, they did not
observe a significant association between serum endrin levels and gestational age (see Table 2-1 for
additional details). Due to elevation of several other organochlorine pesticides in case subjects
(e.g., heptachlor, dieldrin, DDT), no conclusion regarding a potential association between endrin exposure
and preterm delivery can be made.
A cohort study in Kazakhstan reported delayed physical and sexual development in adolescent females
exposed to organochlorine pesticides (lindane, dieldrin, DDT, and endrin) in cotton-growing regions
compared with age-matched controls living in non-cotton-growing regions (Bapayeva et al. 2016). The
study specifically reported a decrease in serum follicle stimulating hormone and estradiol in the exposed
females; however, a statistical analysis is not provided. No significant associations between serum male
or female reproductive hormone levels and serum endrin levels were observed in a cross-sectional study
of a rural area in Brazil with heavy pesticide contaminations (Freire et al. 2014). In vitro screens showed
that endrin does not have a high estrogenic potential (Lemaire et al. 2006; Mumtaz et al. 2002; Tully et al.
2000)
No exposure-related effects on fertility, gestation, viability, or lactation indices were observed in a

three-generation reproduction study in rats fed diets containing endrin at doses up to 0.1 mg/kg/day
(Eisenlord et al. 1968). Interpretation of the study results is confounded by the potential presence of viral
pneumonitis in controls and, thus, possibly in all animals in the study. Similarly, no adverse effects on
fertility or fecundity were observed in mice given diets containing endrin at doses up to 0.65 mg/kg/day

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for 120 days beginning 30 days before mating; however, this dose was associated with reduced litter size
and 30% mortality in breeding pairs (Good and Ware 1969).
One animal study examined reproductive outcomes following oral exposure to endrin, but data quality is
insufficient to characterize an effect level. In a single-generation reproduction study, groups of three
female Beagle dogs were administered dietary doses of 0.0, 0.003, 0.014, 0.027, or 0.059 mg/kg/day and
mated with endrin-treated males from a concurrent chronic toxicity study (Kettering 1971). Four treated
females (one each at 0.014 and 0.027 mg/kg/day and two at 0.059 mg/kg/day) never accepted a male and,
despite artificial insemination, did not become pregnant. The failure to conceive in the high-dose groups
could suggest an endrin-mediated effect on fertility; however, exploratory laparotomies and necropsies,
and microscopic examination of ovaries and uteri at termination of these dogs revealed no specific
changes due to endrin. Furthermore, two of three control dogs failed to bring any pups to weaning and
dogs were infected with Brucella canis infections. Due to these confounding factors, this study in
considered inadequate to make a NOAEL/LOAEL determination for reproductive effects.
2.17 DEVELOPMENTAL
Data on the potential for endrin to cause developmental effects in humans are limited. In an Egyptian
study of 123 pregnancies, associations between maternal or cord serum endrin levels and birth weight,
length, or head circumference appear to be significant (reported p-values of ≤0.001); however, the
associations are not marked as significant in study data tables, and the study authors only discuss the
significant associations between birth outcomes and serum heptachlor and DDT levels (Samra and Selim
2009). The reasons for this apparent discrepancy are unclear based on the reported data. In a birth cohort
with 220 mother-son pairs born in Granada between 2000 and 2002, detection of endrin in the placenta
was associated with a significant 2-fold increase in the risk of “moderately” elevated cord blood TSH
levels, as defined by the World Health Organization (>5 mU/L) (Freire et al. 2011). A subset of mother-
son pairs from this birth cohort were evaluated in a case-control study of male infant cryptorchidism
and/or hypospadias; placental endrin levels were comparable between cases and controls (Fernandez et al.
2007).
Animal studies have observed malformations and variations in mice and hamsters following maternal
exposure to endrin via gavage, predominantly at doses that caused maternal toxicity. Exposure of mice to
2.5 mg/kg on GD 9 resulted in significantly increased incidence of open eyes and cleft palate (Ottolenghi
et al. 1974). Increased incidence of exencephaly, fused ribs, and supernumerary ribs were seen in
offspring of pregnant mice treated with ≥7 mg/kg of endrin on GD 8; increased maternal mortality was

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also observed at this dose (Kavlock et al. 1985). There were no dose-related indications of skeletal or
visceral malformations or anomalies in the mice following maternal exposure to doses up to 2 mg/kg/day
via gavage on GDs 7–17, but delays in development (changes in the number of caudal vertebrae,
development of the renal pelvis, and ossification of the supraoccipital bones) and maternal toxicity were
observed at doses ≥1 mg/kg/day (Kavlock et al. 1981). Increased hydronephrosis was reported in mouse
fetuses following maternal exposure to 6 mg/kg on GD 12 (Hassoun and Stohs 1996b). In hamsters, a
statistically significant increase in the incidence of fused ribs and cleft palate was observed in fetuses
from golden Syrian hamsters treated on GD 7, 8, or 9 with 5 mg/kg of endrin (Ottolenghi et al. 1974). A
significant increase in open eye and webbed foot occurred only in fetuses from dams treated on GD 8
(Ottolenghi et al. 1974). A single dose of endrin administered to hamsters on GD 8 produced meningo-
encephaloceles at a doses of ≥5 mg /kg (Chernoff et al. 1979a). Exposure of hamsters to ≥1.5 mg/kg/day
on GDs 5–14 resulted in irregularly shaped supraoccipital bones and visceral abnormalities (Chernoff et
al. 1979a). In both the single and repeated studies by Chernoff et al. (1979a), fetal effects occurred only
at doses with significant maternal toxicity. In contrast, endrin did not cause fetal malformations or
variations in a study in which pregnant hamsters were administered up to 2.5 mg/kg/day from GD 4 to 13
(Goldenthal et al. 1978b). In rats, no malformations were observed in offspring following maternal
exposure to doses up to 0.45 mg/kg/day from GD 7 to 20 (Kavlock et al. 1981) or 2 mg/kg/day on GDs 6–
15 (Goldenthal et al. 1978a). However, delayed ossification of sternebrae and skull along with maternal
toxicity (decreased weight gain and death) were observed at 2 mg/kg/day (Goldenthal et al. 1978a).
Gestational exposure studies have observed inconsistent effects on fetal survival and resorptions that may
depend on the exposure window, dose, strain, and/or species. Increased incidence of dead or resorbed
fetuses following gestational exposure occurred in C56BL/6J mice exposed to 6 mg/kg on GD 12
(Hassoun and Stohs 1996b) and hamsters exposed to either 5 mg/kg on GD 8 (Ottolenghi et al. 1974) or
≥1.5 mg/kg/day from GD 5 to 14 (Chernoff et al. 1979a). Hassoun and Stohs (1996b) also reported
significant reductions in placental weight in C57BL/6J mice at doses ≥4.5 mg/kg and DBA/2J mice at
6 mg/kg. Other studies did not observe changes in fetal survival in rats exposed to gavage doses up to
0.3 mg/kg/day from GD 7 to 15 (Gray et al. 1981), DBA/2J mice exposed to gavage doses up to 6 mg/kg
on GD 12 (Hassoun and Stohs 1996a), CD-1 mice exposed to a single gavage dose of 2.5 mg/kg on GD 9
(Ottolenghi et al. 1974), hamsters exposed to gavage doses up to 1.5 mg/kg/day from GD 5 to 14 (Gray et
al. 1981), or hamsters exposed to a single oral dose up to 10 mg/kg on GD 8 (Chernoff et al. 1979a).
Gestational studies have also reported decreased fetal growth following gestational exposure to endrin,
predominantly at maternally toxic doses (>0.5 mg/kg/day). In rats, nonsignificant decreases in fetal body

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weight and crown-rump length were observed following maternal exposure to 2 mg/kg/day from GD 6 to
15; this dose caused significant maternal toxicity and death (Goldenthal et al. 1978a). No changes in fetal
weight or growth were observed in rat offspring at maternal doses ≤0.5 mg/kg/day (Goldenthal et al.
1978a; Gray et al. 1981; Kavlock et al. 1981). In mice, a 4–28% decrease in fetal body weight was
reported in C57BL/6J and DBA/2J mice following a single maternal dose to 4.5 or 6 mg/kg/day on
GD 12; no changes in maternal body weight were noted (Hassoun and Stohs 1996b). C57BL/6J mice
also showed a 13–17% decrease in fetal thymus weights at ≥4.5 mg/kg/day. In CD-1 mice, decreased
fetal body weight was observed following maternal exposure to doses ≥1 mg/kg/day from GD 7 to 17;
decreased maternal weight gain was also observed at these doses (Kavlock et al. 1981). In hamsters,
decreased fetal body weight was observed at maternally toxic doses ≥1.5 mg/kg/day (Chernoff et al.
1979a; Ottolenghi et al. 1974). However, no changes in postnatal offspring growth or physical
development were observed in hamsters following maternal exposure to gavage doses up 1.5 mg/kg/day
on GDs 5–14, respectively (Gray et al. 1981).
Data regarding pup survival and growth from generational exposure studies are difficult to interpret due
to several study limitations. A 3-generation reproduction study in rats found no exposure-related changes
in pup viability or survival through weaning at dietary doses up to 0.1 mg/kg/day (Eisenlord et al. 1968).
The number of pups in the F3a litter of the high-dose group was significantly increased relative to
controls, while F3a pup body weight in the low-dose group was significantly decreased. However,
interpretation of the study results is confounded by high death rate in controls attributed to putative viral
pneumonitis. Lack of organ weight or morphologic changes in dog pups from a single-generation study
evaluating dietary doses up to 0.059 mg/kg/day is also difficult to interpret due to the low number of
treated animals, presence of a Brucella canis infection, and failure of two of three control dogs to bring
any pups to weaning (Kettering 1971).
One study observed altered neurodevelopment in rat offspring following maternal exposure to endrin at
doses ≥0.15 mg/kg/day from GD 7 to 15 (Gray et al. 1981). Exposed offspring showed increased activity
in the last 30 minutes of a 45-minute figure-eight maze trail on postnatal day (PND) 15 and PND 20,
indicating a lack of normal habituation to a new environment. This effect was no longer apparent on
PND 90, and may have been a result of delayed maturation of cholinergic and serotonergic
neurotransmission networks. A similar effect was observed in hamster offspring following maternal
exposure to 1.5 mg/kg/day on GDs 5–14 (Gray et al. 1981). It should be noted that increases in maternal
mortality was also observed at 1.5 mg/kg/day in the hamsters.

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2.18 OTHER NONCANCER
Acute exposure to 8.2 mg/kg/day endrin in the diet for 1–2 days resulted in a significant 41–51% decrease
in serum glucose (Ali and Shakoori 1993). In the absence of additional data, the biological significance
of this finding is unclear.
2.19 CANCER
Studies of workers in the endrin manufacturing industry have not shown an association between
occupational exposure to endrin and overall mortality rates due to cancer (Ditraglia et al. 1981; Ribbens
1985; Versteeg and Jager 1973); see Table 2-1 for study details. While there was no specific cancer risk
at any manufacturing sites, several cancer mortalities reported in aldrin/ dieldrin/endrin plants in one
study may warrant further investigation, including slight excesses of cancer of the esophagus, liver,
rectum, and the lymphatic and hematopoietic systems (Ditraglia et al. 1981). However, the study authors
noted that excesses were not statistically significant, and acknowledged that the elevated standardized
mortality ratios (SMRs) were based on small numbers of observed deaths (one to three deaths except for
lymphatic/hematopoietic cancers, which were based on six deaths). Limitations of these studies include
small cohort size, limited follow-up, and lack of control for confounding factors (e.g., smoking, alcohol
consumption).
Several case-control studies have evaluated potential associations between organochlorine pesticide
exposure and specific types of cancer. Available studies on breast cancer (Boada et al. 2012; Ward et al.
2000), bladder cancer (Boada et al. 2016), prostate cancer (Pi et al. 2016), and lymphoma (Cocco et al.
2008) did not find detectable endrin levels in any cancer subjects. In these studies, detection of endrin
levels varied widely in control subjects (endrin detected in 0–58% of controls). These studies are
inadequate to evaluate potential associations between endrin and cancer due to low detection rate and
unknown exposure potentials.
Endrin was found not to be carcinogenic in Osborne-Mendel rats exposed to dietary doses up to
0.25 mg/kg/day (males) or 0.30 mg/kg/day (females) or B6C3F1 mice exposed to dietary doses up to
0.42 mg/kg/day (males) or 0.65 mg/kg/day (females) for 80 weeks (NCI 1978). However, the study’s
less-than-lifetime exposure duration limits its conclusions. Deichmann et al. (1970) also reported a lack
of exposure-related neoplastic findings in Osborn-Mendel rats in a lifetime dietary study; however, this
study was also limited because it only included microscope examination of the liver, kidneys, and lungs.

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Only one study reported carcinogenic effects of endrin, but its design limitations render the findings
unreliable. Reuber (1978) observed increased incidence of sarcoma and carcinomas in multiple tissues
combined (e.g., mammary gland, lungs, liver, lymph nodes, thyroid, uterus and kidney) in Osborne-
Mendel rats following lifetime dietary exposure to doses ranging from 0.005 to 1.25 mg/kg/day.
However, the findings were not dose-related (higher incidence at the lower doses). Based on statistics
performed for this review, only mammary gland carcinoma incidence in female rats exposed to
0.5 mg/kg/day (14/23) and 0.25 mg/kg/day (13/20) and thyroid carcinoma in female rats exposed to
1.25 mg/kg/day (4/19) were significantly elevated compared with control (6/23 and 0/23, respectively).
With the exception of mammary gland and thyroid carcinomas, tumor incidence per organ was only one
to two animals. Study limitations include the low number of animals studied (15–23/sex/group), several
inconsistencies in data reporting, and concerns regarding Reuber’s methods for classifying tissues as
tumorigenic (as identified by IRIS 2002), including a lack of slide-by-slide tabulation of study findings as
well as no attempt to distinguish between primary and metastatic tumors in the liver. Due to these
reasons, the reliability of these findings is questionable, and this study is not included in the LSE.
2.20 GENOTOXICITY
Available evidence indicates that endrin is not mutagenetic. There is limited evidence that it is capable of
causing DNA damage and chromosomal alterations under certain conditions; however, endrin-mediated
oxidative damage generally causes the observed DNA damage, rather than direct interaction with DNA.
Tables 2-5 and 2-6 summarize the results of in vitro and in vivo genotoxicity studies with endrin,
respectively.
Table 2-5. Genotoxicity of Endrin In Vitro
Results
Activation
Species (test system) Endpoint With Without Reference
Prokaryotic organisms
Salmonella typhimurium Gene mutation – – Glatt et al. 1983
strains TA98, TA100
S. typhimurium strains TA97, Gene mutation – – Mersch-Sundermann
TA98, TA100, TA102, A1535, et al. 1994
TA1537
S. typhimurium strains TA98, Gene mutation – – Moriya et al. 1983
TA100, TA1535, TA1537,
TA1538

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2. HEALTH EFFECTS
Table 2-5. Genotoxicity of Endrin In Vitro
Results
Activation
Species (test system) Endpoint With Without Reference
S. typhimurium strains TA98, Gene mutation – – Probst et al. 1981
TA1000, TA1535, TA1537,
TA1538, C3076, D3052, G46
Salmonella typhimurium Gene mutation – – Zeiger 1987
strains TA98, TA100, A1535,
TA1537
Escherichia coli strain WP2 Gene mutation – – Moriya et al. 1983
E. coli strains WP2, WP2 Gene mutation – – Probst et al. 1981
uvrA-
E. coli strain PQ37 DNA damage NA + Venket et al. 1995
(modified SOS
chromotest)
E. coli strain PQ37 DNA damage (SOS – – Mersch-Sundermann
chromotest) et al. 1994
Mammalian cells
Rat (liver epithelial ARL cells) HGPRT mutations NA – Williams 1980
Mouse (lymphoma L5178Y Gene mutation – – McGregor et al. 1991
tk+/- cells)
Human (lymphoid cells) Sister chromatid – – Sobti et al. 1983
exchange
Rat (primary hepatocytes) DNA damage/repair – NA Maslansky and
Williams 1981
Rat (primary hepatocytes) Unscheduled DNA – NA Probst et al. 1981
synthesis
Rat (primary hepatocytes) DNA damage/repair – NA Williams 1980
Rat (neuroactive adrenal DNA damage (single NA + Bagchi et al. 1995a
pheochromocytoma PC-12 strand breaks)
cells)
Mouse (primary hepatocytes) DNA damage/repair – – Maslansky and
Williams 1981
Hamster (primary DNA damage/repair – NA Maslansky and
hepatocytes) Williams 1981
Hamster (primary DNA damage/repair – NA Williams 1980
hepatocytes)
– = negative result; + = positive result; DNA = deoxyribonucleic acid; NA = not applicable

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2. HEALTH EFFECTS
Table 2-6. Genotoxicity of Endrin In Vivo
Species (exposure route) Endpoint Results Reference

Mammals
Rat (oral) DNA damage in brain and liver + Bagchi et al. 1995a
(single strand breaks)
Rat (oral) DNA damage in brain and liver + Bagchi et al. 1995b
(single strand breaks)
Rat (oral) DNA damage in liver (single + Bagchi et al. 1992a
strand breaks)
Rat (oral) DNA damage in liver (single + Bagchi et al. 1993a
strand breaks)
Rat (oral) DNA damage in liver (single + Bagchi et al. 1993c
strand breaks)
Rat (oral) DNA damage in liver (single + Hassoun et al. 1993
strand breaks)
Mice (oral) DNA damage in brain and + Bagchi et al. 2000
liver(Fragmentation)
Mice (oral) DNA damage in brain and liver + Bagchi et al. 2002
(Fragmentation)
Mice (oral) DNA damage in fetuses, + Hassoun and Stohs 1996a
placenta, and fetal liver tissues
(Single strand breaks)
Rat (intratesticular injection) Chromosomal aberrations in + Dikshith and Datta 1973
testis
Eukaryotic organisms
Drosophila melanogaster Somatic mutation (wing spot +/– Osaba et al. 1999
(oral) test)
D. melanogaster (oral) Recombination + Pontecorvo and Fantaccione
2006
– = negative result; + = positive result; +/– = inconclusive result; DNA = deoxyribonucleic acid
Mutagenicity. Endrin was not mutagenic in microbial systems (Glatt et al. 1983; Mersch-Sundermann et
al. 1994; Moriya et al. 1983; Probst et al. 1981; Zeiger 1987), rat liver epithelial ARL cells (Williams
1980), or mouse lymphoma L5178Y tk +/- cells (McGregor et al. 1991). In a Drosophila wing spot test,
the mutagenicity of endrin was inconclusive due to toxicity, even at the lowest concentrations tested
(0.001 mM); however, the study authors interpreted the results as primarily negative (Osaba et al. 1999).
No studies evaluating in vivo mutagenicity of endrin in mammals were located.
Clastogenicity. Sister chromatid exchanges were not observed in human lymphoid cells exposed to
endrin in vitro (Sobti et al. 1983). In vivo, chromosomal aberrations in rat testicular cells were observed
following an intratesticular injection of endrin (Dikshith and Datta 1973). The number of recombination

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2. HEALTH EFFECTS
events was slightly, but significantly, increased in Drosophila melanogaster males (cross overs detected
in 3 out of 60 males; p=0.05) (Pontecorvo and Fantaccione 2006).
DNA Damage. In Escherichia coli, DNA damage was not observed using the standard SOS chromotest
(Mersch-Sunderann et al. 1994); however, DNA damage was observed when endrin was tested in a
modified SOS chromotest using sodium taurocholate micelles to better simulate conditions in the small
intestine (Venkat et al. 1995). In mammalian cells, endrin did not cause DNA damage or repair or
unscheduled DNA synthesis in rat, mouse, or hamster primary hepatocytes (Maslansky and Williams
1981; Probst et al. 1981; Williams 1980). A small, but significant (2.5-fold) increase in nuclear DNA
single-strand breaks was detected in rat neuroactive adrenal pheochromocytoma PC-12 cells cultured with
100 nM endrin, compared with controls (Bagchi et al. 1995a).
Several studies reported increased DNA single strand breaks in liver (up to 4.4-fold) and brain tissues (up
to 4.3-fold) of rats and mice following acute oral exposure to endrin (Bagchi et al. 1995a,1995b, 1992a,
1993a,1993c, 2000, 2002; Hassoun et al. 1993). Evidence of concurrent production of reactive oxidative
species was observed in these studies, indicating that DNA damage was secondary to oxidative injury
caused by endrin. Additionally, pre-administration of lazaroid U74389F (16-desmethyl tirilazad)
decreased both generation of reactive oxidative species and DNA single strand breaks (Bagchi et al.
1995b). DNA damage was greater in p53-deficient mice (up to 3.9- and 4.4-fold increase in liver and
brain tissue, respectively) compared with wild-type mice (up to 2.6- and 1.8-fold increase in liver and
brain tissue, respectively), indicating a role for the p53 tumor suppressor gene in observed oxidative DNA
damage (Bagchi et al. 2000).
Hassoun and Stohs (1996a) evaluated the potential role of the Ah receptor in observed DNA damage in
placental, fetal, and fetal liver tissue following a single oral exposure to endrin on GD 12. Results
showed a greater increase in DNA single strand breaks in Ah-responsive C57BL/6J mice than in
Ah-unresponsive DBA/2J mice, particularly in placenta (3.2- and 2-fold, respectively) and fetal liver
tissues (4.67- and 1.39-fold, respectively).
2.21 MECHANISMS OF TOXICITY
General, systemic mechanisms of endrin toxicity may include altered metal homeostasis, generation of
reactive oxygen species, and glutathione depletion.

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2. HEALTH EFFECTS
Several oral rat studies reported altered metal homeostasis following exposure to endrin. Altered trace
metal distribution was observed systemically in rats exposed once to a gavage dose of 25 mg/kg/day
(Lawrence et al. 1968). Changes included significant increases in zinc concentrations in the liver, kidney,
spleen, brain, and heart with decreased blood cell zinc levels; decreases copper concentrations in the liver,
spleen, brain, and heart with elevated serum plasma levels; increases in magnesium concentration in
kidney, spleen, and heart; decreases in magnesium concentrations in the liver, brain, red blood cells, and
plasma; and increases in iron concentrations of the liver, kidney, spleen, and heart. Similarly, altered
metal homeostasis was reported in rats following administration of 8 mg/kg of endrin over 8 days
(3 mg/kg on day 1, 2 mg/kg on days 3 and 5, and 1 mg/kg on day 8, with findings indicating increased
magnesium excretion and decreased zinc excretion (Coleman et al. 1968). Bagchi et al. (1992c) also
reported altered metal homeostasis in the liver following a single exposure to ≥3 mg/kg, including
increases in mitochondrial iron and calcium, decreases in microsomal and nuclear iron, and increases in
microsomal and nuclear calcium.
Oral administration of endrin to rats was associated with increased lipid peroxidation, increased excretion
of metabolites indicative of lipid peroxidation, decreased membrane fluidity, DNA damage (single strand
breaks), and induction of protective heat shock (stress) proteins in hepatocytes and brain tissue (Bagchi et
al. 1995a,1995b, 1992a, 1992b, 1993a, 1993c, 1996, 2000, 2002; Hassoun and Stohs 1996a; Hassoun et
al. 1993, 1996). Administration of antioxidants ameliorated some of the adverse observations. Similar
effects have been observed in placental tissue, fetal tissue, and fetal livers (Hassoun and Stohs 1996a),
and increased levels of metabolites indicative of lipid peroxidation have been reported in urine, maternal
sera, amniotic fluids, and placenta following acute exposure to endrin (Bagchi et al. 1992b; Hassoun and
Stohs 1996a; Hassoun et al. 1996). Therefore, generation of reactive oxygen species may represent a
general mechanism by which endrin exerts toxicity, potentially through activation of the PKC pathway,
which could lead to altered cell proliferation and differentiation (Bagchi et al. 1997).
Limited evidence indicates that endrin may deplete glutathione. Numan et al. (1990a, 1990b) reported
that endrin exposure was associated with decreased glutathione concentrations in liver, kidney, heart,
spleen, brain, and lungs, and altered glutathione-regulating enzymes in liver and kidney.

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CHAPTER 3. TOXICOKINETICS, SUSCEPTIBLE POPULATIONS,

BIOMARKERS, CHEMICAL INTERACTIONS
3.1 TOXICOKINETICS
Limited data were found regarding the absorption, distribution, metabolism, and excretion of endrin in
humans and animals after inhalation, oral, or dermal exposure. Available data are summarized below.
• Toxic effects following oral, inhalation, or dermal exposure indicate that the body absorbs endrin
via all routes; however, data regarding absorption rates are very limited.
• Endrin is primarily distributed to fat and skin.
• The major biotransformation product of endrin is anti-12-hydroxyendrin and the corresponding
sulfate and glucuronide metabolites.
• Endrin is excreted in urine and feces.
• No studies were found that described the toxicokinetics of endrin aldehyde or endrin ketone.
3.1.1 Absorption
Quantitative data describing the rate of absorption of endrin following inhalation exposure were not
available. Cases of occupational exposure reported by Hoogendam and coworkers (1965) and laboratory
animal studies reported by Treon et al. (1955) indicate that when endrin is inhaled and absorbed, it can
produce serious adverse biological effects.
Reported toxic effects in case studies indicate that humans absorb endrin following ingestion (Coble et al.
1967; Curley et al. 1970; Kintz et al. 1992; Rowley et al. 1987; Runhaar et al. 1985; Weeks 1967).
Similarly, numerous animal studies reported serious adverse biological effects following oral exposure,
indicating absorption. However, no studies have been located that report the rate or extent of absorption
that occurs in orally exposed humans or animals.
No studies were located regarding absorption of endrin in humans after dermal exposure. Agricultural
worker exposure studies demonstrated that dermal exposure (18.7 mg/hour without gloves) was
significantly greater than respiratory exposure (0.41 mg/hour) and that workers exposed to endrin
received about 0.2–1.5% of a toxic dose per hour of exposure (Wolfe et al. 1963).

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3. TOXICOKINETICS, SUSCEPTIBLE POPULATIONS, BIOMARKERS, CHEMICAL INTERACTIONS
Dermal exposure of rats and rabbits to endrin resulted in toxicity and death (Gaines 1960; Treon et al.
1955), indicating that percutaneous absorption of endrin occurs. Data describing the rate or extent of
dermal absorption in animals were not located.
3.1.2 Distribution
No studies were located regarding distribution of endrin in humans or animals after inhalation exposure.
Measurable tissue concentrations of endrin have been observed in cases of acute oral poisoning. The time
of sample collection is critical, as endrin residues in tissues decline rapidly after exposure has ceased
(Coble et al. 1967). Evaluations shortly after exposure (<1 hour) have shown the highest concentrations
in the gastrointestinal system and liver, followed by the kidney, spleen, and heart (Coble et al. 1967;
Curley et al. 1970; Kintz et al. 1992; Moriya and Hashimoto 1999; Tewari and Sharma 1978). Blood and
bile concentrations were low compared to organ levels in all cases except those with rapid death (Kintz et
al. 1992). Evaluations at a later time point show a different pattern; 11 days after a suicide attempt, the
highest concentration was identified in the adipose tissue, followed by much lower levels in the liver,
heart, brain, kidneys, and blood (Runhaar et al. 1985). In the general population, low levels of endrin in
the adipose tissue of Jordanian men and woman generally increased with age (Alawi et al. 1999);
however, studies in the United States and Canada did not find measurable levels of endrin in adipose
tissue of the general population (Stanley 1986; Williams et al. 1984).
Endrin tends to bioaccumulate in fat because of its high lipid solubility. Three days after an acute oral
dose of 2.5 mg/kg of radio-labeled endrin, the percentages of the administered dose in male rat organs
were 1.2% in liver, 0.6% in kidney, 1.7% in fat, 2.3% in skin, and 12.2% in the carcass. Female rats
retained higher concentrations in tissues: 2% of the dose in liver, 0.35% in kidney, 8% in fat, 4% in skin,
and 28.2% in carcass (Hutson et al. 1975). Richardson et al. (1970) also reported an unidentified
metabolite of endrin in the brain, liver, and adipose tissue of male rats following a single oral exposure.
Following administration of radiolabeled endrin to lactating cows, the highest tissue concentrations were
in the fat (about 8% of the total dose). Residues in liver, muscle, kidneys, and fat primarily contained
unchanged endrin (Baldwin et al. 1976). Endrin and 12-ketoendrin were detected in the maternal liver
and fetal tissue of rats and hamsters administered endrin during gestation (Chernoff et al. 1979a; Kavlock
et al. 1981). Concentrations of endrin in fetal tissue ranged from 2 to 8% of those measured in maternal
livers, indicating that endrin can cross the placenta.

ENDRIN 72
In Beagle dogs that had died after apparent ingestion of endrin-containing bait, the stomach contents
contained 34–5,000 mg/kg endrin (Quick et al. 1989). The highest tissue concentrations were found in
the fat (5.4–40 mg/kg), followed by liver (0.82–4.5 mg/kg) and brain (0.34–2.7 mg/kg). Lower
concentrations were found in lung and muscle. Following administration of 0.1 mg/kg/day in the feed for
128 days, concentrations of endrin in the blood of Beagle dogs showed no accumulation over time
(Richardson et al. 1967). At termination, there was no correlation between the concentration of endrin in
blood with that in heart, pancreas, liver, kidney, spleen, and lung, although a trend of high concentrations
in fat (250–760 ppb) and high concentrations in blood (1–8 ppb) were noted. The highest tissue
concentrations of endrin were generally found in fat, followed by muscle (120–310 ppb), heart (125–
170 ppb), pancreas (87–280), liver (77–84 ppb), kidney (38–82 ppb), and lung (17–33 ppb).
Concentrations in the spleen were highly variable (7–2,620 ppb). Results from this study may be
somewhat confounded by a potential feeding error, as dieldrin (being fed to a concurrent group) was
detected in the blood and tissues of the three endrin-treated dogs.
No studies were located regarding distribution of endrin in humans or animals after dermal exposure.
3.1.3 Metabolism
The metabolism of endrin varies among species, regardless of the route of exposure. In all species,
oxidation of the methylene bridge in endrin (Compound I in Figure 3-1) to syn-, but mostly anti-
12-hydroxyendrin occurs (Compounds II and III), followed by dehydrogenation to 12-ketoendrin
(Compound VI). Minor independent pathways involve the hydrolysis of the epoxide to a transdiol
(Compound V in Figure 3-1) and hydroxylation of the C-3 position (Compound IV) (Bedford et al.
1975b; Hutson 1981; Petrella et al. 1977). Hydroxylation at C-3 and C-4 is inhibited by the presence of
the bulky hexachlorinated fragment (Hutson 1981). In rats, both anti-12-hydroxyendrin and
12-ketoendrin are produced at higher rates in the male rat, with higher formation of anti-12-hydroxy-
endrin O-sulphate in female rats (Hutson et al. 1975). Richardson et al. (1970) also reported sex
differences in the proportion of fecal metabolites in rats; however, metabolites were identified as “1” and
“2” and not further characterized except to state that they were not ketone rearrangement products of
endrin. In mice, strains resistant to acute endrin toxicity produce anti-12-hydroxyendrin at higher rates
(~2-fold) compared with strains that are susceptible to acute endrin toxicity (Petrella et al. 1977).

ENDRIN 73
Figure 3-1. Proposed Metabolism Scheme for Endrin in Mammals
HO H HSO3O H
O O
Cl Cl
O (VII)
Cl
Cl Cl Cl
O Gluc O H
(II)
O
(VI)
H OH (VIII)
O
H OSO3H
Major
Cl Cl O
Cl
Cl Cl Cl
(IX)
(III)
Major
Glucuronide
O (X)
O
Minor
Cl OH
Cl Cl Cl Sulfate
Cl (XI)
Cl
Cl Cl Cl
Cl Cl Cl
(IV) Glucuronide
(I) (XII)
Minor
OH
Sulfate
OH
(XIII)
Cl Cl
Cl
Glucuronide
Cl Cl Cl
(XIV)
(V)

ENDRIN 74
Hydroxylated metabolites are conjugated as glucuronides and sulfates. The balance of products in this
last step and their distribution between urine and feces distinguishes the metabolism between humans,
rats, and rabbits (Baldwin and Hutson 1980; Bedford et al. 1975b; Hutson 1981; Hutson et al. 1975).
Similarly, studies in lactating cows ingesting radiolabeled endrin in the diet for 21 days suggest metabolic
pathways similar to those in rats and rabbits with apparent differences between the three species attributed
more to differences in biliary versus renal excretion (Baldwin et al. 1976).
In workers in pesticide manufacturing plants, anti-12-hydroxyendrin as the glucuronide and 12-ketoendrin

were found in both urine and feces (three of seven workers) (Baldwin and Hutson 1980).
Anti- and syn-12-hydroxyendrin and 12-ketoendrin are more toxic in the rat than endrin itself. The
hydroxyendrins are rapidly converted to the more toxic 12-ketoendrin, and this latter metabolite is most
likely the toxic entity of endrin (Bedford et al. 1975a; Hutson et al. 1975).
3.1.4 Excretion
Measurements of human serum concentrations of endrin following incidents of acute poisoning indicate
rapid decline in concentration after exposure, suggesting rapid excretion (Coble et al. 1967; Rowley et al.
1987). Anti-12-hydroxyendrin and 12-ketoendrin were detected in the feces of pesticide manufacturing
workers and its glucuronide conjugate and 12-ketoendrin have been detected in the urine (Baldwin and
Hutson 1980). In another study, the levels of anti-12-hydroxyendrin increased accompanied by a sharp
rise in D-glucaric acid levels in 29 workers after 7 days of exposure (Ottevanger and Van Sittert 1979;
Vrij-Standhardt et al. 1979). Endrin has also been detected in human breast milk, cord blood, and
placental tissues in several studies worldwide (Alawi et al. 1992; Bedi et al. 2013; Bordet et al. 1993 Fujii
et al. 2012; Gladen et al. 1999; Guillette et all. 1998; Lopez-Espinosa et al. 2007; Polanco-Rodriguez
2017; Romero et al. 2000; Schaalan et al. 2012). Endrin, endrin aldehyde, and endrin ketone may also be
excreted in humans via sweat (Genuis et al. 2016).
In rats, the bulk of endrin metabolites excreted by rats are in the bile as glucuronides (Hutson et al. 1975).
Rabbits excrete 14C-endrin in the urine as sulfates (Bedford et al. 1975b). Studies in lactating cows
ingesting endrin in the diet for 21 days show that 14C-endrin is readily excreted as unchanged endrin in
the milk, accounting for 2.5–4.3% of the total dose (Baldwin et al. 1976). Due to its lipophilic nature
(partition coefficient [Logow]: 5.6), endrin was contained in the lipid portion of the milk.

ENDRIN 75
In rats, the major route of elimination is the feces, with a smaller percentage eliminated in the urine, and
there are apparent sex differences. Twenty-four hours after oral exposure to 0.5–2.5 mg/kg, 55–57% of
14
C-endrin was metabolized in the bile; the predominant metabolite was the glucuronide of anti-
12-hydroxyendrin (Hutson et al. 1975). Other minor components (<10%) were the glucuronides of
3-hydroxy- and 12-ketoendrin. Male rats eliminated 69% of the radioactive label within 3 days and
females eliminated 45%. Another study in male rats reported elimination of 49% of the radioactive label
within 3 days following oral exposure (Richardson et al. 1970). In studies with isolated perfused livers,
14
C-endrin was excreted in the bile of livers from male rats at a rate 2–12 times higher than that for
females (Klevay 1971). In urine, the major metabolites in males and females were 12-ketoendrin and
12-hydroxyendrin-O-sulfate, respectively, following oral exposure (Hutson et al. 1975). Baldwin et al.
(1970) also detected 9-ketoendrin in the urine of rats.
In rabbits administered radiolabeled endrin, 50% of the radioactivity was excreted in the urine over a
50-day period (Bedford et al. 1975b). Excretion of the label was 87% complete within 13 days. The
major compounds detected in urine were anti-12-hydroxyendrin sulfate and 3-hydroxyendrin sulfate
(14%).
No studies were located concerning excretion of endrin in animals after inhalation or dermal exposure.
3.1.5 Physiologically Based Pharmacokinetic (PBPK)/Pharmacodynamic (PD) Models
PBPK models use mathematical descriptions of the uptake and disposition of chemical substances to
quantitatively describe the relationships among critical biological processes (Krishnan et al. 1994). PBPK
models are also called biologically based tissue dosimetry models. PBPK models are increasingly used in
risk assessments, primarily to predict the concentration of potentially toxic moieties of a chemical that
will be delivered to any given target tissue following various combinations of route, dose level, and test
species (Clewell and Andersen 1985). Physiologically based pharmacodynamic (PBPD) models use
mathematical descriptions of the dose-response function to quantitatively describe the relationship
between target tissue dose and toxic endpoints.

ENDRIN 76
No chemical-specific PBPK models have been developed for endrin.
3.1.6 Animal-to-Human Extrapolations
No studies were identified that could evaluate potential differences in the toxicity or toxicokinetics of
endrin between humans and animals. However, the primary toxicity target (nervous system) is consistent
between exposed humans and animals. Some species differences were observed between different
laboratory species; however, the targets of toxicity appear to be similar. Available mechanistic data are
inadequate to evaluate potential species differences.
3.2 CHILDREN AND OTHER POPULATIONS THAT ARE UNUSUALLY SUSCEPTIBLE
This section discusses potential health effects from exposures during the period from conception to
maturity at 18 years of age in humans. Potential effects on offspring resulting from exposures of parental
germ cells are considered, as well as any indirect effects on the fetus and neonate resulting from maternal
exposure during gestation and lactation. Children may be more or less susceptible than adults to health
effects from exposure to hazardous substances and the relationship may change with developmental age.
This section also discusses unusually susceptible populations. A susceptible population may exhibit
different or enhanced responses to certain chemicals than most persons exposed to the same level of these
chemicals in the environment. Factors involved with increased susceptibility may include genetic
makeup, age, health and nutritional status, and exposure to other toxic substances (e.g., cigarette smoke).
These parameters can reduce detoxification or excretion or compromise organ function.
Populations at greater exposure risk to unusually high exposure levels to endrin are discussed in
Section 5.7, Populations with Potentially High Exposures.
Persons with a history of convulsive disorders are expected to be at increased risk of nervous system
effects if exposed to endrin. Data are inadequate to determine if children may be more sensitive than
adults to the acute toxic effects of endrin. In an endrin poisoning episode in Pakistan, children 1–9 years
old represented about 70% of the cases of convulsions (Rowley et al. 1987). The causative factor
responsible for the outbreak was not identified, however, so it is unclear whether the age distribution of
cases is due to increased susceptibility in children or age-specific exposure situations. In general,
following oral administration, female animals appear to be more susceptible to endrin toxicity than males
(Gaines 1960; Treon et al. 1955). The difference may be due to the more rapid excretion of endrin by

ENDRIN 77
male versus female rats (Hutson et al. 1975; Klevay 1971; Korte et al. 1970). A sex-related difference in
toxicity was not apparent following dermal exposure (Gaines 1960, 1969). No sex-based differences in
endrin-related human toxicity have been documented. For example, an equal number of male and female
patients were affected in the endrin poisoning episode in Pakistan (Rowley et al. 1987). Genetic
differences in metabolism may also alter susceptibility to endrin toxicity as well, as a heritable resistance
in pine mice to endrin raises the LD50 from as low as 1.37 mg/kg in sensitive strains to as high as
36.4 mg/kg in resistant strains (Webb et al. 1973). This trait is correlated with the higher amounts of
detoxifying enzymes in resistant mice.
3.3 BIOMARKERS OF EXPOSURE AND EFFECT
Biomarkers are broadly defined as indicators signaling events in biologic systems or samples. They have
been classified as biomarkers of exposure, biomarkers of effect, and biomarkers of susceptibility
(NAS/NRC 1989).
A biomarker of exposure is a xenobiotic substance or its metabolite(s) or the product of an interaction

between a xenobiotic agent and some target molecule(s) or cell(s) that is measured within a compartment
of an organism (NAS/NRC 1989). The preferred biomarkers of exposure are generally the substance
itself, substance-specific metabolites in readily obtainable body fluid(s), or excreta. Biomarkers of
exposure to endrin are discussed in Section 3.3.1. The National Report on Human Exposure to
Environmental Chemicals provides an ongoing assessment of the exposure of a generalizable sample of
the U.S. population to environmental chemicals using biomonitoring (see http://www.cdc.gov/
exposurereport/). If available, biomonitoring data for endrin from this report are discussed in Section 5.6,
General Population Exposure.
Biomarkers of effect are defined as any measurable biochemical, physiologic, or other alteration within an
organism that (depending on magnitude) can be recognized as an established or potential health
impairment or disease (NAS/NRC 1989). This definition encompasses biochemical or cellular signals of
tissue dysfunction (e.g., increased liver enzyme activity or pathologic changes in female genital epithelial
cells), as well as physiologic signs of dysfunction such as increased blood pressure or decreased lung
capacity. Note that these markers are not often substance specific. They also may not be directly
adverse, but can indicate potential health impairment (e.g., DNA adducts). Biomarkers of effect caused
by endrin are discussed in Section 3.3.2.

ENDRIN 78
A biomarker of susceptibility is an indicator of an inherent or acquired limitation of an organism's ability

to respond to the challenge of exposure to a specific xenobiotic substance. It can be an intrinsic genetic or
other characteristic or a preexisting disease that results in an increase in absorbed dose, a decrease in the
biologically effective dose, or a target tissue response. If biomarkers of susceptibility exist, they are
discussed in Section 3.2, Children and Other Populations that are Unusually Susceptible.
3.3.1 Biomarkers of Exposure
Levels of endrin or endrin metabolites can be measured in tissue and excreta, thereby serving as
biomarkers of exposure. Further, measurements of endrin in blood are best suited for detecting recent
exposures because endrin is cleared rapidly from blood. The lack of persistence of endrin in human
tissues and blood seen in the study of Coble et al. (1967) indicates a brief half-life for endrin on the order
of 1–2 days. Sera levels of endrin (time to sample not specified) in Pakistani patients who were poisoned
with endrin ranged from 0.3 to 254 ppb (0.3–254 µg/L); survivors had sera levels that ranged from 1.3 to
17.4 ppb (1.3–17.4 µg/L) (Rowley et al. 1987). An endrin concentration of 0.3 ppb was detected in the
cerebrospinal fluid. Hair may be a useful biomarker for prior exposure to endrin. Smith-Baker and Saleh
(2011) demonstrated a sensitive method of endrin detection in hair that accurately distinguished
occupationally exposed workers from the general public.
Measurements of endrin metabolites can also be useful in monitoring endrin exposure. The glucuronides
of anti-12-hydroxyendrin and I2-ketoendrin have been detected in feces and urine (Baldwin and Hutson
1980). The anti-12-hydroxyendrin glucuronide marker is the most sensitive and specific urinary marker.
D-glucaric acid is a nonspecific marker that may indicate prior exposure to endrin (Hunter et al. 1972;
Ottevanger and Van Sittert 1979; Vrij-Standhardt et al. 1979). High levels of D-glucaric acid were
detected in workers for up to 6 weeks, after which levels returned to normal ranges (Ottevanger and Van
Sittert 1979).
Endrin levels in fat tissues may only be a useful biomarker after high occupational exposure, as endrin has
only been detected in the adipose tissue of workers after very high exposures and not in the general
population (Stanley 1986; Williams et al. 1988). Endrin has been detected in the milk of lactating women
(0.02–6.24 mg/kg milk fat) (Alawi et al. 1992; Bordet et al. 1993).

ENDRIN 79
3.3.2 Biomarkers of Effect
Changes in the nervous system are the most common effects associated with human exposure to endrin.
Various signs and symptoms of exposure include twitching of muscles, dizziness, mental confusion, and
epileptiform seizures (Carbajal-Rodriquez et al. 1990; Coble et al. 1967; Curley et al. 1970; Davies and
Lewis 1956; Hoogendam et al. 1962, 1965; Rowley et al. 1987; Runhaar et al. 1985; Waller et al. 1992;
Weeks 1967). However, these effects also occur following exposure to other organochlorine pesticides
and other drugs, and are not specific to endrin.
3.4 INTERACTIONS WITH OTHER CHEMICALS
The toxicity of endrin may be influenced by interactions with other chemicals and physical agents,
particularly other organochlorine pesticides.
Quails treated with endrin and chlordane had significantly lower endrin residues in brain tissue (p<0.025)
than birds treated with endrin alone (Ludke 1976). It is not clear how co-administration of chlordane
altered tissue distribution of endrin; however, the authors attributed this difference to the presence of one
or more metabolites of chlordane in the nervous system. However, despite differences in endrin residues,
toxicity of endrin was not altered by prior exposure to chlordane; 15/20 animals died within 10 days of
daily endrin exposure and 14/20 animals died within 10 days of daily endrin exposure following 10 weeks
of chlordane exposure (Ludke 1976).
Keplinger and Deichmann (1967) evaluated potential interactions between endrin and several other
pesticides based on observed versus expected LD50 values in mice. After determining LD50 values for
each compound, the expected LD50 value of a mixture was calculated and compared to the observed LD50
value of the mixture. The study authors considered ratios between 0.79 and 1.27 essentially additive, with
higher ratios indicating greater-than-additive effects, and lower ratios indicating less-than-additive effects.
Greater-than-additive effects were noted for endrin and chlordane (ratio of 2.22) and for endrin and aldrin
(ratio of 1.83). The interactions observed for endrin plus dieldrin, diazinon, toxaphene, or malathion were
additive, and the interactions observed for endrin plus parathion, DDT, and Delnav were less than
additive (ratios of 0.65, 0.53, and 0.44, respectively). When a mixture of aldrin, chlordane, and endrin
was administered, observed effects were considered additive (ratio of 1.27).
In an in vitro estrogenic potential assay, binary mixtures of organochlorine compounds (DDT, DDD,
DDE, aldrin, dieldrin, endrin) did not increase estrogenic activity compared with estradiol; additional

ENDRIN 80
testing with individual compounds also found no significant dose-related estrogenic activity (Mumtaz et
al. 2002; Tully et al. 2000). More studies are needed to better identify and characterize potential
synergistic effects of endrin with other compounds.
Pohl and Tylenda (2000) conducted binary weight-of-evidence (WOE) determinations of the potential for
joint toxic action between endrin and other organochlorine pesticides. Based on their analyses, there is
direct mechanistic data indicating a synergistic effect between endrin and the following organochlorines:
DDT, aldrin, dieldrin, chlordane, hexachlorobenzene (HCB), and ɑ-, β-, and δ-hexachlorocyclohexane
(HCH). For γ-HCH, there is direct mechanistic data indicating an antagonistic effect on endrin.
Demonstrated toxicological significance was only available for chlordane (see Ludke 1976 above); for the
remaining compounds, Pohl and Tylenda (2000) inferred toxicological significance.

ENDRIN 81
CHAPTER 4. CHEMICAL AND PHYSICAL INFORMATION
4.1 CHEMICAL IDENTITY
Information regarding the chemical identity of endrin, endrin aldehyde, and endrin ketone is located in
Table 4-1.
4.2 PHYSICAL AND CHEMICAL PROPERTIES
Information regarding the physical and chemical properties of endrin, endrin aldehyde, and endrin ketone
is located in Table 4-2.

ENDRIN 82
4. CHEMICAL AND PHYSICAL INFORMATION
Table 4-1. Chemical Identity of Endrin, Endrin Aldehyde, and Endrin Ketone
Characteristic Endrin Endrin aldehyde Endrin ketone Reference

Chemical name 2,7:3,6-Dimethano- 1,2,4-Methenocyclo- 2,5,7-Metheno-3H-cyclo- EPA 1984a
naphth(2,3-b)oxirene, penta(cd)-entalene- penta(a)entalen-
3,4,5,6,9,9-hexachloro- 5-carboxaldehyde, 3-one,3b,4,5,6,6a-hexa-
1a,2,2a,3,6,6a,7,7a-octa- 2,2a,3,3,4,7-hexachloro- chlorodecahydro-
hydro- (1aα,2β,2aβ,3α,6α, deca-hydro- (1α,2β,2aβ,4β, (2α,3aβ,3bβ,4β,5β,6aβ,7α,
6aβ,7β,7aα)- 4aβ,5β,6aβ,6bβ,7R*) 7aβ,8R*)
Synonym(s) Endrin; 1,2,3,4,10,10-hexa- Endrin aldehyde; Endrin ketone HSDB 1995
chloro-6,7-epoxy- 1,2,4-methanecyclopenta
1,4,4A,5,6,7,8,8A- octa- (c,d)pentalene-
hydro-endo, endo- 5-carboxaldehyde,
1,4:5,8-dimethano- 2,2a,3,3,4,7-hexachloro-
naphthalene, and others decahydro
Registered trade name(s) Mendrin, Hexacrin, Endrex No data Delta-keto 153 NLM 1988; Sittig 1980
experimental insecticide
269
Chemical formula C12H8Cl6O C12H8Cl6O C12H8Cl6O EPA 1984a
Chemical structure Cl Cl Cl EPA 1984a
Cl
Cl Cl Cl
Cl Cl
Cl Cl
Cl
Cl Cl
Cl O Cl
Cl H H Cl
O O
CAS registry 72-20-8 7421-93-4 53494-70-5 EPA 1984a
CAS = Chemical Abstracts Services

ENDRIN 83
Table 4-2. Physical and Chemical Properties of Endrin, Endrin Aldehyde, and Endrin Ketone
Property Endrin Endrin aldehyde Endrin ketone Reference

Molecular weight 380.9 381.9 380.9 EPA 1984a
Color White, colorless No data No data HSDB 1995; IARC 1974;
Worthington and Walker
Physical state Crystalline solid Solid Solid EPA 1984; HSDB 1995;
IARC 1974
Melting point 235°C; 226–230°C (decomposes) 145–149°C; 235°C No data EPA 1981; HSDB 1995;
(decomposes) Worthington and Walker
1983
Boiling point Decomposes at 246°C; No data No data ACGIH 1986; HSDB 1995;
decomposes above 200°C IARC 1974
Density at 20°C No data No data No data
Odor 1.7 at 20°C No data No data EA 1980a; HSDB 1995
Odor threshold:
Water 0.041 mg/L Verschueren 1983
Air 1.8x10-2 ppm No data No data Fazzalara 1978
Solubility:
Water 200 µg/L at 20°C 50 mg/L; 0.25–0.26 ppm No data EPA 1981a
Organic solvents Acetone:17 g/100 mL; benzene No data No data HSDB 1995; Merck 1989
13.8 g/100 mL; carbon
tetrachloride: 3.3 g/100 mg/L;
hexane: 7.1 g/100 mL; xylene:
18.3 g/100 mL
Partition coefficients:
Log Kow 5.6, 5.34 (calculated), 5.45 3.146, 4.7, 5.6 (calculated) 4.99 (calculated) EPA 1981a; HSDB 1995;
(calculated) SRC 1995b
Koc 4.532 (calculated); 5.195 (±0.005) 4.80 (calculated); 3.929–4.653 No data De Bruijin et al. 1989;
(calculated) HSDB 1995; Kenaga 1980
Vapor pressure 2.0x10-7 mmHg 2.0x10-7 mmHg No data EPA 1981a; HSDB 1995;
Worthington and Walker
1983

ENDRIN 84
Table 4-2. Physical and Chemical Properties of Endrin, Endrin Aldehyde, and Endrin Ketone
Property Endrin Endrin aldehyde Endrin ketone Reference

Henry's law constant 4.0x10-7 atm-m3/mol
(calculated);2x10-9 atm-m3/mol; 2.02x10-8 atm-m3/mol EPA 1981a; HSDB 1995;
5.4x10-7 atm-m3/mol (calculated) 2.9x10-9 atm-m3/mol; SRC 1994a; Thomas 1982
3.67x10-8 atm-m3/mol
(calculated)
Autoignition temperature No data No data No data
Flashpoint Non-flammable Non-flammable No data HSDB 1995
Flammability limits No data No data No data
Conversion factors 1 ppm=15.6 mg/m3 1 ppm=15.6 mg/m3 1 ppm=15.6 mg/m3
1 mg/m3=0.06 ppm 1 mg/m3=0.06 ppm 1 mg/m3=0.06 ppm
Explosive limits No data No data No data

ENDRIN 85
CHAPTER 5. POTENTIAL FOR HUMAN EXPOSURE
5.1 OVERVIEW
Endrin, endrin aldehyde, or endrin ketone has been identified in at least 176 of the 1,854 hazardous waste
sites that have been proposed for inclusion on the EPA National Priorities List (NPL) (ATSDR
2017). However, the number of sites in which endrin, endrin aldehyde, or endrin ketone has been
evaluated is not known. The number of sites in each state is shown in Figure 5-1. Of these sites, 175 are
located within the United States and 1 is located in the Virgin Islands (not shown).
Figure 5-1. Number of NPL Sites with Endrin Contamination
• The most likely route of exposure to endrin for the general population is via ingestion of endrin
residues on imported food items. Endrin is no longer used in the United States
• Environmental exposure is expected to be low. Exposure to small amounts may occur following
unregistered use, inappropriate disposal, or at hazardous waste sites.
• Currently, there are no significant releases of endrin into the environment, but endrin persists in
sorbed forms to sediments and soil from previous use.
• The estimated half-life of endrin in soil is approximately 14 years. It is not expected to migrate
from soil to groundwater.

ENDRIN 86
5. POTENTIAL FOR HUMAN EXPOSURE
• Endrin transformation products including, endrin ketone, endrin aldehyde, and endrin alcohol,
can be detected in plants grown in soils treated at least 16 years prior to planting.
5.2 PRODUCTION, IMPORT/EXPORT, USE, AND DISPOSAL
5.2.1 Production
No information is available in the TRI database on facilities that manufacture or process endrin because
this chemical is not required to be reported under Section 313 of the Emergency Planning and Community
Right-to-Know Act (Title III of the Superfund Amendments and Reauthorization Act of 1986) (EPA
2005).
Endrin is a stereoisomer of dieldrin produced by the reaction of vinyl chloride and hexachlorocyclo-
pentadiene to yield a product that is then dehydrochlorinated and condensed with cyclopentadiene to
produce isodrin. This intermediate is then epoxidized with peracetic or perbenzoic acid to yield endrin.
An alternative production method involves condensation of hexachlorocyclopentadiene with acetylene to
yield the intermediate for condensation with cyclopentadiene (EPA 1985e; IARC 1974).
Endrin is no longer manufactured in the United States. Velsicol Chemical Company, Memphis,
Tennessee, was the producer of endrin until the final voluntary cancellation of registration with the Office
of Pesticide Programs in 1991 (Bishop 1984, 1985, 1986; EPA 1983e; USDA 1995). It is estimated that
2.345 million kg (5.1–9.9 million pounds) of endrin were sold in the United States in 1962, while
<450,000 kg (990,000 pounds) were produced in 1971 (IARC 1974). More recent estimates of domestic
production of endrin could not be found (HSDB 1995). As with many toxic chemicals, information on
production or use of pesticides is often proprietary, and quantitative estimates of production of endrin are
virtually impossible to obtain (Bason and Colbom 1992). Chemical manufacturers in the United States
however, can legally produce pesticides for export that are currently banned or not registered for use in
the United States (FASE 1996).
Endrin aldehyde and endrin ketone were never commercial products, but occurred as impurities of endrin
or as degradation products (EPA 1985e; IARC 1974; SRI 1987). While commercial preparations of solid
endrin were typically 95–98% pure, the following chemicals (in addition to endrin aldehyde and endrin
ketone) have been found as trace impurities: aldrin, dieldrin, isodrin, heptachloronorbornadiene, and
heptachloronorborene (HSDB 1995). The active ingredient would often be mixed with one or more

ENDRIN 87
organic solvents for application in a liquid form. Carriers included xylene, hexane, and cyclohexane
(HSDB 1995; Zabik et al. 1971).
5.2.2 Import/Export
Data on historic imports and exports of endrin are sparse. The most recent data that could be located
indicate that about 21,000 kg (46,000 pounds) of endrin were imported into the United States in 1972
(IARC 1974). No information on export volumes of endrin was located. However, the Foundation for
Advancements in Science and Education reported that almost 75% of the 750,000 tons of pesticides the
United States exported from 1992 to 1994 lacked chemical-specific information (FASE 1996). Many of
the exported pesticides were organochlorine pesticides that had been banned for use in the United States.
5.2.3 Use
Endrin was first used as an insecticide, rodenticide, and avicide beginning in 1951 to control cutworms,
voles, grasshoppers, borers, and other pests on cotton, sugarcane, tobacco, apple orchards, and grain (EPA
1979e; HSDB 1995). It was also used as an avicide on enclosed bird perches (EPA 1985f). Unlike
aldrin/dieldrin, with which it has many chemical similarities, endrin apparently was never used
extensively for termite-proofing or other applications in urban areas (Blus et al. 1989; HSDB 1995).
Endrin’s toxicity to nontarget populations of raptors and migratory birds was a major reason for its
cancellation as a pesticide agent (Blus et al. 1989; EPA 1979f; USDA 1995). Except for use as an avicide
on bird perches, which was canceled in 1991, all other uses of endrin in the United States were voluntarily
canceled by the manufacturer in 1986 (Bishop 1984, 1985, 1986; EPA 1983e; USDA 1995). It has been
estimated that 6,250 kg (13,780 pounds) of endrin were used annually in the United States prior to 1983
(Gianessi 1986). Since endrin may still be used as a pesticide agent in foreign countries, residues on
imported food items are still of some concern (FDA 1990, 1991, 1992; Hundley et al. 1988). Both the
EPA and the Food and Drug Administration (FDA) revoked all food tolerances for endrin in 1993 (USDA
1995).
5.2.4 Disposal
Because endrin and endrin aldehyde are listed as hazardous substances, disposal of wastes containing
these compounds is controlled by a number of federal regulations (see Chapter 7). Land disposal
restrictions apply to wastes containing endrin or endrin aldehyde (EPA 1986d, 1987b). Chemical
treatment (reductive dechlorination) or incineration are possible disposal methods (HSDB 1995; IRPTC

ENDRIN 88
1985). Past disposal methods included land disposal (EPA 1987c; Sittig 1980). In general, disposal
methods for endrin residues or endrin-containing wastes are similar to those for wastes containing
aldrin/dieldrin (HSDB 1995). No information was found in the available literature on regulations or
methods for the disposal of endrin ketone.
No information was found in the available literature on the amounts of endrin, endrin aldehyde, or endrin
ketone disposed of in the United States by any method.
5.3 RELEASES TO THE ENVIRONMENT
The Toxics Release Inventory (TRI) data should be used with caution because only certain types of
facilities are required to report (EPA 2005). This is not an exhaustive list. Manufacturing and processing
facilities are required to report information to the TRI only if they employ ≥10 full-time employees; if
their facility is included in Standard Industrial Classification (SIC) Codes 10 (except 1011, 1081, and
1094), 12 (except 1241), 20–39, 4911 (limited to facilities that combust coal and/or oil for the purpose of
generating electricity for distribution in commerce), 4931 (limited to facilities that combust coal and/or
oil for the purpose of generating electricity for distribution in commerce), 4939 (limited to facilities that
combust coal and/or oil for the purpose of generating electricity for distribution in commerce), 4953
(limited to facilities regulated under RCRA Subtitle C, 42 U.S.C. section 6921 et seq.), 5169, 5171, and
7389 (limited S.C. section 6921 et seq.), 5169, 5171, and 7389 (limited to facilities primarily engaged in
solvents recovery services on a contract or fee basis); and if their facility produces, imports, or processes
≥25,000 pounds of any TRI chemical or otherwise uses >10,000 pounds of a TRI chemical in a calendar
year (EPA 2005).
Because virtually all uses of endrin in the United States were voluntarily canceled by 1986 (Bishop 1984,
1985, 1986; EPA 1993e; USDA 1995), releases to the environment of endrin, or endrin aldehyde and
endrin ketone, which occur as impurities or degradation products of endrin, have decreased dramatically
over the last decade.
5.3.1 Air
There is no information on releases of endrin to the atmosphere from manufacturing and processing
facilities because these releases are not required to be reported (EPA 2005).

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In the past, emissions from endrin production and processing facilities and agricultural applications were
primary sources of releases of endrin to the atmosphere. During the period when endrin was extensively
used in agriculture, 33% of the applied endrin was found to volatilize within 11 days, after which time
further evaporation ceased (Nash 1983).
There is also a potential for atmospheric release of endrin, endrin aldehyde, and endrin ketone from
hazardous waste sites.
5.3.2 Water
There is no information on releases of endrin to water from manufacturing and processing facilities
because these releases are not required to be reported (EPA 2005).
In the past, endrin could have been released to surface water from manufacturing and processing
facilities. No information on direct discharges or loadings of endrin into surface water was found. Based
on amounts measured in rainfall at various stations in Canada, loading estimates for endrin and a number
of other organochlorine pesticides have been attempted for portions of the Great Lakes basin (Strachan
1988). The sources for such loadings to receiving waters are not clear, but would likely involve in-place
contaminants related to endrin’s past uses as a pesticide agent. A 1995 study conducted in Oklahoma
indicates that in some areas of the United States, endrin can be released to surface water from farmland
soils that have been treated with endrin in the past (Petty et al. 1995).
There is also a potential for release of endrin, endrin aldehyde, and endrin ketone to water from hazardous
waste sites.
5.3.3 Soil
There is no information on releases of endrin to soil from manufacturing and processing facilities because
these releases are not required to be reported (EPA 2005).
Past use of endrin as an agricultural pesticide has been the principal source of its release to soils or
aquatic sediments. There is also a potential for release of endrin, endrin aldehyde, and endrin ketone to
soils and sediments from hazardous waste sites.

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5.4 ENVIRONMENTAL FATE
5.4.1 Transport and Partitioning
Endrin is extremely persistent when released to the soil. It adsorbs strongly to soil particles and tends to
be immobile, based on an estimated Koc of 34,000 (Kenaga 1980; Swann et al. 1983). Endrin on soil may
be transported to surface water via runoff from rain or irrigation. Since endrin in solid form is
hydrophobic and sorbs strongly to soil particles, migration into groundwater would not generally be
expected from normal agricultural application. In laboratory studies, endrin was found to be almost
completely adsorbed to samples of sandy loam and organic soil (Sharom et al. 1980a). In sandy soil, only
13.6% of the endrin was leached from the soil after 10 successive 200 mL water rinses. In organic soil,
only 1.5% of the endrin was leached from the soil after 10 successive 200 mL water rinses. The mobility
factors calculated for the sandy soil and organic soil were 0.52 and 0.040, respectively. Only dieldrin,
leptophos, and p,p’-DDT were less mobile than endrin in the two soil types.
However, endrin has been detected in groundwater, suggesting that leaching may be possible in some
soils under certain conditions (Cohen 1986; EPA 1989). Furthermore, because endrin formulations in
solvent carriers such as xylene or hexane were also commonly used, endrin could move into groundwater
from spills of such formulations. Similarly, migration to groundwater might also occur at waste sites
where endrin residues become mixed with organic solvents (Jaquess et al. 1989).
Despite endrin’s low vapor pressure of 2.0x10-7 mm Hg (EPA 1981a), initial volatilization of 20–30%
after agricultural application to soil has been reported to be rapid (Nash 1983). Within 11 days, however,
further volatilization was no longer detected (Nash 1983). Unlike some other chlorinated pesticides,
endrin volatilization was not enhanced after a rainfall. Small amounts of endrin in soil may also be
transported to the air by dust particles.
The presence of significant concentrations of endrin transformation products (including endrin ketone,
endrin aldehyde, and endrin alcohol) in a variety of plants grown in soil treated with endrin for periods as
long as 16 years prior to planting (Beall et al. 1972; Nash and Harris 1973) indicates that there may be
significant uptake of endrin and/or its transformation products by plants from endrin-treated soil.
Because of its high log Koc and log Kow values (4.53 and 5.34–5.6, respectively; see Table 4-2), when
released to water, endrin strongly adsorbs to sediment (Kenaga 1980; Swann et al. 1983) and
bioconcentrates significantly in aquatic organisms (ASTER 1995; EPA 1980a; Metcalf et al. 1973).

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Typical bioconcentration factors (BCFs) for freshwater and marine organisms range from 80 to
49,000 (Table 5-1). Biomagnification of endrin with increasing trophic level is not expected to be
significant (Leblanc 1995). Metcalf et al. (1973) reported a ratio of biomagnification through the aquatic
food chain to bioconcentration by direct uptake from water to be 2 for endrin compared to 2.50 for DDT.
These authors used a model laboratory aquatic ecosystem containing algae (Oedogonium cardiacurn),
snails (Physa sp.), water fleas (Daphnia magna), mosquito larvae (Culex pipiens quinquefasciatus), and
mosquito fish (Gambusia afinis).
Table 5-1. Bioconcentration Data for Endrin
Exposure Duration
Species common name (scientific name) type (days) BCFa Reference
Freshwater
Algae (Microcystis aeruginosa) – 7 200 Vance and Drummond1969
(as cited in EPA 1980a)
Algae (Anabaena cylindrica) – 7 222 Vance and Drummond1969
Algae (Scenedesmus quadricauda) – 7 156 Vance and Drummond1969
Algae (Oedogonium sp.) – 7 140 Vance and Drummond1969
Water flea (Daphnia magna) S 1 2,600 Metcalf et al. 1973
Mosquito (Culex pipiens quinquefasciata) S 1 2,100 Metcalf et al. 1973
Stonefly (Pteronarcys dorsata) F 28 1,000 Anderson and Defoe 1980
Pouch snail (Physa sp.) S 33 49,000 Metcalf et al. 1973
Mussels (mixed species) – 21 3,000 Jarvinen and Tyo 1978
Channel catfish (Ictalurua punctatus) – 41–55 2,000 Argyle et al. 1973 (as cited
in EPA 1980a)
Flagfish (Jordanella floridae) – 65 15,000 Hermanutz 1978
Flagfish (J. floridae) F 15 7,000 Hermanutz et al. 1985
Fathead minnow (Pimephales promelas) F 47 10,000 Mount and Putniki 1966 (as
cited in EPA 1980a)
Fathead minnow (P. promelas) – 56–300 7,000 Jarvinen and Tyo 1978
Fathead minnow (P. promelas) F 2–304 80b Veith and Kosian 1983
Black bullhead (Ictalurus melas) F 4 3,700 Anderson and Defoe 1980
Black bullhead (I. melas) F 7 6,200 Anderson and Defoe 1980
Saltwater
Grass shrimp (Palaemonetes pugio) F 145 1,600 Tyler-Schroeder 1979
American oyster (Crassostrea virginica) F 2 1,670 Mason and Rowe 1976
American oyster (C. virginica) F 7 2,780 Mason and Rowe 1976
Sheepshead minnow, embryo-juveniles – 33 4,800 Schimmel et al. 1975 (as
(Cyprinodon variegatus) cited in EPA 1980a)

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Table 5-1. Bioconcentration Data for Endrin
Exposure Duration
Species common name (scientific name) type (days) BCFa Reference
Sheepshead minnow (C. variegatus) – 141–161 6,400 Hansen et al. 1977
Spot (Leiostomos xanthurus) – 5– 1,450 Lowe 1966 (as cited in EPA
8 months 1980a)
aBCF listed is the highest bioconcentration factor (BCF) value reported in the cited reference.
bCalculated quantitative structure-activity relationship (QSAR) value.
F = flow-through exposure system; S = static system
Based on its very small calculated Henry’s law constant of 4.0x10-7–5.4x10-7 atm-m3/mol (see Table 4-2)
and its strong adsorption to sediment particles, endrin would be expected to partition very little from
water into air (Thomas 1990). The half-life for volatilization of endrin from a model river 1 meter deep,
flowing 1 meter per second, with a wind speed of 3 meters per second, was estimated to be 9.6 days,
whereas a half-life of >4 years was estimated for volatilization of endrin from a model pond (Howard
1991). Adsorption of endrin to sediment may reduce the rate of volatilization from water.
In air, endrin is expected to be associated primarily with particulate matter based on its low vapor
pressure and high Koc (Kenaga 1980). However, small amounts of endrin in the atmosphere may exist in
the vapor phase (Eisenreich et al. 1981). Because of its low solubility (200 µg/L, see Table 4-2), endrin
would not be expected to be removed significantly from the atmosphere by wet deposition. Particle-
adsorbed endrin will be removed from the atmosphere by both wet and dry deposition. Endrin was found
in 5% of 450 wet deposition (rain/snow) samples collected between 1986 and 1991 in the Great Lakes
area, at volume weighted mean concentrations ranging from 0.02 to 0.98 ng/L (ppt) (Chan et al. 1994).
No studies on the environmental transport and partitioning of endrin aldehyde could be found in the
available literature. Values of the estimated log Kow for endrin aldehyde vary widely, ranging from 3.1 to
5.6 (see Table 4-2). Based on the lowest estimated log Kow, the Koc value for endrin aldehyde can be
estimated to be approximately 1,000 (Lyman 1990), indicating a low mobility in soil (Swann et al. 1983).
Using the higher estimated values of log Kow (4.7–5.6), the Koc value for endrin aldehyde can be estimated
to range from 8,500 to 380,000 (Lyman 1990), indicating that this compound will be virtually immobile
in most soils (Swann et al. 1983). Because of its low vapor pressure of 2.0x10-7 mmHg and Henry’s Law
constant ranging from 2x10-9 to 3.7x10-8 atm-m3/mol (see Table 4-2), endrin aldehyde would not be
expected to volatilize significantly from soil or water (Eisenreich et al. 1981; Thomas 1990). Any endrin
aldehyde in air should exist predominantly in the adsorbed phase (Eisenreich et al. 1981). Atmospheric

ENDRIN 93
endrin aldehyde will be transported to soil and surface water via wet and dry deposition of associated
particles. In water, adsorption to sediments and bioconcentration are likely to be significant partitioning
processes. Based on the lowest estimated value of 3.1 for log Kow (see Table 4-2), the BCF value for
endrin aldehyde can be estimated to be only 86 (Veith et al. 1979), indicating little tendency to
bioconcentrate in aquatic organisms. Using the higher estimates of 4.7–5.6 for log Kow (see Table 4-2),
BCF values for endrin aldehyde are estimated to range from to 2,000 to 11,000 (Veith et al. 1979),
indicating a much higher tendency for bioconcentration.
No studies on the environmental transport or partitioning of endrin ketone could be found in the available
literature, and only limited information was found on estimated values of physical and chemical
properties. The very low estimated value of 2.02x10-8 atm-m3/mole for Henry’s Law constant for endrin
ketone (see Table 4-2) indicates that this compound will not volatilize from water. Based on the
estimated log Kow of 4.99 (see Table 4-2), the BCF value for endrin ketone can be estimated to be
3,500 (Veith et al. 1979), indicating that endrin ketone may be removed from water via bioconcentration
in aquatic organisms. Also based on an estimated log Kow of 4.99, the Koc value for endrin ketone can be
estimated to range from 5,500 to 90,000 (Lyman 1990), indicating that this compound will be virtually
immobile in soil and sediments (Swann et al. 1983).
5.4.2 Transformation and Degradation
Air. Field studies on the transformation of endrin in the atmosphere were not located in the available
literature. Photochemical isomerization of endrin, primarily to the pentacyclic ketone commonly called
delta ketoendrin or endrin ketone, was observed after exposure of thin layers of solid endrin on glass to
sunlight (Burton and Pollard 1974). Minor amounts of endrin aldehyde were also formed in this reaction.
Results of seasonal studies indicated that this isomerization would proceed with a half-life (first-order
kinetics) of 5–9 days in intense summer sunlight, with complete conversion to the pentacyclic ketone in
15–19 days. Knoevenagel and Himmelreich (1976) reported that photodegradation of solid endrin in the
laboratory proceeded with a half-life (first-order kinetics) of 20–40 hours. In laboratory studies
conducted by Zabik et al. (1971) on endrin formulations in hexane and cyclohexane (similar to those
commonly used for pesticide applications), endrin was found to undergo photolytic dechlorination when
exposed to ultraviolet radiation, yielding a pentachlorinated half-cage ketone as the major product. This
degradation product was also detected in environmental samples. Endrin may also be transformed by heat
in the atmosphere, yielding primarily the pentacylic ketone and endrin aldehyde (EPA 1979g; Phillips et
al. 1962). Endrin may also react with photochemically generated hydroxyl radicals in air, with a

ENDRIN 94
predicted half-life (first-order kinetics) ranging from 1.45 hours (Howard 1991) to 1.8 days (SRC 1995a).
No information could be found on the products of this reaction. The reaction of endrin with ozone in air
is not significant. The predicted first-order rate constant for this reaction is 3.6x10-20 cm3/molecule-
second, corresponding to a half-life of 320 days (SRC 1995a).
Endrin aldehyde may react with photochemically generated hydroxyl radicals in the atmosphere, with an
estimated overall first-order rate constant of 106x10-12 cm3/molecule-second, which corresponds to a half-
life of 3.6 hours, assuming a 24-hour concentration of hydroxyl radicals of 0.5x106 molecules/cm3 (SRC
1995a). Endrin ketone may react with photochemically generated hydroxyl radicals in the atmosphere,
with an estimated overall first-order rate constant of 10.8x10-12 cm3/molecule-set, which corresponds to a
half-life of 1.5 days, assuming a 24-hour concentration of hydroxyl radicals of 0.5x106 molecules/cm3
(SRC 1995a). No other information could be found in the available literature on the transformation and
degradation of endrin aldehyde or endrin ketone in air.
Water. Laboratory studies of the fate of endrin in water samples suggest a significant degree of
stability, although there is evidence of varying degrees of biodegradation in some systems. Endrin was
among the more stable of 12 insecticides incubated in water collected from the drainage canal of a
vegetable-growing site near Toronto, with about 80% of endrin remaining in the natural water after
incubation for 16 weeks (Sharom et al. 1980b). There was little indication of chemical degradation of
endrin in these studies. Studies in which sealed water samples from the Little Miami River were exposed
to sunlight and artificial fluorescent light showed no measurable degradation of endrin over an 8-week
period (Eichelberger and Lichtenberg 1971). However, microorganisms in fish pond water and algae
from a fish pond were able to metabolize endrin (Patil 1972). In the case of the algae, the metabolite was
12-ketoendrin. The rate of metabolism was 35% for the water sample and 24% for the algal culture in
1 month. Using the static culture procedure, Tabak et al. (1981) found no biodegradation of endrin in
domestic waste water samples.
Based on laboratory experiments on solid endrin (Burton and Pollard 1974) and on endrin in organic
solvents (Zabik et al. 1971), it is likely that endrin released to surface water will undergo photo-
isomerization to endrin ketone, with minor amounts of endrin aldehyde also being formed. Under real
world conditions, endrin released to surface waters would not be expected to biodegrade or hydrolyze to
any significant extent (Eichelberger and Lichtenberg 1971; EPA 19798). Endrin is very resistant to
hydrolysis, with an estimated half-life (first-order kinetics) of >4 years (EPA 1979g). The predominant
removal of endrin from water by photodegradation and sorption to suspended particulates or sediments is

ENDRIN 95
consistent with the observed low incidence of detected endrin in ambient surface waters based on
analyses of EPA National Urban Runoff Program (Cole et al. 1984) and STORET (Staples et al. 1985)
data.
Little information could be found in the available literature on the transformation and degradation of
endrin aldehyde in water. Neither hydrolysis nor oxidation (via peroxy radicals or singlet oxygen) are
expected to be significant in aquatic systems (EPA 1981a). By analogy to endrin, the hydrolysis half-life
(first-order kinetics) of endrin aldehyde in water is probably >4 years (EPA 1979g). No information
could be found on the biodegradation of endrin aldehyde in aquatic systems.
No information could be found in the available literature on the transformation and degradation of endrin
ketone in water.
Sediment and Soil. Biodegradation does not appear to be a significant degradation process for endrin
in soils. The actual measurement of biodegradation of endrin under field conditions on well-drained
agricultural soil indicates a biodegradation half-disappearance time of approximately 14 years (Nash and
Woolson 1967), suggesting that endrin is resistant to biodegradation in soils under natural conditions. In
this study, 41% of the initial endrin applied to an agricultural field was present in the soil after 14 years.
Laboratory studies indicate that endrin can be biodegraded in various soils under various conditions;
however, caution should be exercised in extrapolating laboratory results to field conditions. Twenty
different isolates of soil organisms belonging to several different species (five identified, four
unidentified) were found to biodegrade endrin in the laboratory under aerobic conditions (Patil et al.
1970). The study revealed endrin as one of the more easily biodegradable insecticides, while lindane, for
example, was not degraded by any of the 20 isolates. In contrast, Bartha et al. (1967) found no
biodegradation of endrin, but they used rather insensitive analytical techniques compensated for by high
endrin concentrations (0.25 ppm) that would not occur in normal agricultural practice. Nitrification was
enhanced by endrin in this experiment. Endrin was also biodegraded to four unidentified metabolites in
laboratory microcosms using flooded rice soils (Gowda and Sethunathan 1976). The most rapid
degradation was seen in the saline acid sulfate soil, pokkali, followed by alluvial and laterite soils, where
endrin concentrations dropped 10–20-fold in 55 days. Sandy soils were least active and reduced endrin
concentration only by about 40% in 55 days. The addition of organic matter, such as rice straw,
approximately doubled the rate of biodegradation. Half-disappearance times of endrin in soils ranged
from <20 days under optimal conditions to about 80 days under less-favorable conditions. A degradation

ENDRIN 96
half-life (first-order kinetics) of 26–32 weeks was reported for endrin (initial concentration approximately
1.6–2.0 ppm) in a clay soil under controlled, aerobic environmental conditions (30°C; soil water content
10–33%), with slower degradation observed in soils with the lowest moisture content (Ghadiri et al.
1995). First-order rate equations best described the degradation. Virtually complete anaerobic
biodegradation of endrin in laboratory microcosms within 4 days has been reported; however, the
researchers caution that under natural conditions, redox environments in many soils will not be suitable
for anaerobic degradation, and that endrin residues sorbed to soil particles would often be rendered
unavailable to bacteria (Maule et al. 1987).
In combination, losses from volatilization, photodegradation (Burton and Pollard 1974; EPA 1985e;
Knoevenagel and Himmelreich 1976; Zabik et al. 1971), and heat transformation (primarily to endrin
ketone, with minor amounts of endrin aldehyde) (EPA 1979g; Phillips et al. 1962) are likely to account
for a rapid decrease in endrin residues on soil or plant surfaces exposed to bright sunlight. Studies have
also been conducted indicating significant concentrations of endrin transformation products (including
endrin ketone, endrin aldehyde, and endrin alcohol) in plants grown in endrin-treated soil (Beall et al.
1972; Nash and Harris 1973).
Little information could be found in the available literature on the transformation and degradation of
endrin aldehyde in sediment and soil. By analogy to aquatic systems, neither hydrolysis nor oxidation
(via peroxy radicals or singlet oxygen) would be expected to be significant transformation processes. No
information could be found on the biodegradation of endrin aldehyde in sediment or soil.
No information could be found in the available literature on the transformation and degradation of endrin
ketone in sediment and soil.
5.5 LEVELS IN THE ENVIRONMENT
Reliable evaluation of the potential for human exposure to endrin depends, in part, on the reliability of
supporting analytical data from environmental samples and biological specimens. Concentrations of
endrin in unpolluted atmospheres and in pristine surface waters are often so low as to be near the limits of
current analytical methods. In reviewing data on endrin levels monitored or estimated in the
environment, it should also be noted that the amount of chemical identified analytically is not necessarily
equivalent to the amount that is bioavailable.

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Table 5-2 shows the lowest limit of detections that are achieved by analytical analysis in environmental
media.
Table 5-2. Lowest Limit of Detection Based on Standardsa
Media Detection limit Reference

Air No data Harkov 1986; Ligocki and Pankow
1985
Water 0.006 ppb EPA 1982a
Soil/sediment 2–3 ppb Carey et al. 1976
Blood serum 5.09–7.8 ng/g lipid CDC 2018
aDetection limits based on using appropriate preparation and analytics. These limits may not be possible in all
situations.
Detections of endrin in air, water, and soil at NPL sites are summarized in Table 5-3.
Table 5-3. Endrin, Endrin Aldehyde and Endrin Ketone Levels in Water, Soil, and
Air of National Priorities List (NPL) Sites
Geometric Number of
Geometric standard quantitative
Medium Mediana meana deviationa measurements NPL sites
Endrin
Water (ppb) 0.35 0.65 62,200 16 13
Soil (ppb) 1,810 1,160 53,700 25 24
Air (ppbv) 0.0013 0.0024 3,940 7 4
Endrin aldehyde
Water (ppb) 0.17 0.099 28,900 6 5
Soil (ppb) 6.05 86.8 104,000 20 17
Air (ppbv) No data
Endrin ketone
Water (ppb) 0.47 0.62 18,200 12 8
Soil (ppb) 52 202 27,700 27 20
Air (ppbv) No data
aConcentrations found in ATSDR site documents from 1981 to 2017 for 1,854 NPL sites (ATSDR 2017). Maximum
concentrations were abstracted for types of environmental media for which exposure is likely. Pathways do not
necessarily involve exposure or levels of concern.

ENDRIN 98
5.5.1 Air
Endrin is relatively nonvolatile with a vapor pressure of 2.0x10-7 mmHg (EPA 1981a; Worthing and
Walker 1983). Despite its low volatility, initial loss of agriculturally applied endrin through volatilization
was found to be comparable to more volatile pesticides (Nash 1983). No recent data on atmospheric
concentrations of endrin could be found in the available literature.
Limited information was found on atmospheric concentrations of endrin between 1970 and the mid-
1980s, prior to cancellation of virtually all uses (Bishop 1984, 1985, 1986; EPA 1993e; USDA 1995).
The data were insufficient to identify any trends. The mean and maximum airborne concentrations of
endrin in the United States in 1970–1971 were reported to be 0.2 and 19.2 ng/m3, respectively (Lee 1977).
For that same time period, mean airborne concentrations at suburban sites near Jackson, Mississippi, and
Columbia, South Carolina, were reported to be 0.1 and 0.2 ng/m3, respectively (Bidleman 1981; Kutz et
al. 1976). Endrin was not detected at Boston, Massachusetts, suburban sites (Bidleman 1981). A survey
of airborne contaminants in the Great Lakes area in 1981 did not detect endrin (Eisenreich et al. 1981).
Atmospheric concentrations of endrin in the vicinity of manufacturing facilities were higher than those
found in non-source areas of the United States. Eight hundred meters from two formulation plants in
Arkansas and 275 meters from one formulation plant in Tennessee, mean airborne concentrations of
endrin were reported to be 3.3 and 3.5 ng/m3, respectively, during 1970–1972 (Lewis and Lee 1976).
Endrin was also detected in air in industrial or source-dominated regions of the Mississippi Delta in
1972–1974, and in Tennessee in 1971 (EPA 1985e).
Endrin may also be found in atmospheric precipitation. In an analysis of pesticides in rainfall from four
stations in Canada in 1984, detectable concentrations of endrin were found at each site (Strachan 1988).
There was a noticeable pattern of decline in detections within the summer season (May–August). In more
recent studies in the Great Lakes area, endrin was found in 5% of 450 wet deposition (rain/snow) samples
collected between 1986 and 1991, at volume weighted mean concentrations ranging from 0.02 to
0.98 ng/L (ppt) (Chan et al. 1994).
No information was found in the available literature on concentrations of endrin aldehyde or endrin
ketone in ambient outdoor air or in indoor air. In addition, no information was available on occupational
exposures to these chemicals.

ENDRIN 99
5.5.2 Water
Very little recent information on concentrations of endrin in water could be found in the available
literature. Unlike DDT, chlordane, aldrin/dieldrin, and a variety of other chlorinated pesticides, endrin
was never used extensively in urban areas. This is reflected in the results from EPA’s Nationwide Urban
Runoff Program, which showed no detections in 86 high-flow water samples from 51 urbanized
watersheds from 19 cities (Cole et al. 1984). Analysis of EPA STORET monitoring information from
ambient surface water showed a significant percentage of detections for endrin (32% of 8,789 samples),
but most were near the detection limits, with a national median concentration of 0.001 ppb (Staples et al.
1985). A similar analysis of STORET data for endrin aldehyde showed that this compound was not
found in 770 samples of ambient surface water. More recently, endrin was not detected (detection limit
49 ng/L [0.045 ppb]) in surface water from the Yakima River Basin, Washington (Foster et al. 1993).
However, in 1991–1992, endrin was detected in first flush (first 20 minutes) stormwater runoff samples at
four of six sites in Louisville, Kentucky, at levels that exceeded U.S. federal criteria (0.003 µg/L, [ppb])
(Marsh 1993). Maximum, minimum, and mean concentrations at the four sites were 0.03–0.05, 0.02–
0.04, and 0.03–0.04 (ppb), respectively. Endrin was not detected (detection limit not specified) in 3-hour
composite samples of stormwater runoff from any of the six sites.
Studies using semipermeable membrane devices to determine bioavailable (dissolved) organochlorine

pesticide residues in streams receiving irrigation rainwater from agricultural activity in the Luger Altus
Watershed in southwestern Oklahoma indicate that endrin may still be present in this aquatic ecosystem
several years after discontinuation of its use (Petty et al. 1995). Calculated concentrations of bioavailable
endrin at six sampling sites ranged from not detected (detection limit not specified) to 110 µg/L (ppb).
Concentrations were higher in spring than in summer. There is an uncertainty in these estimates because
they were derived from the dialysate data using models and preliminary data on uptake kinetics.
Endrin is rarely detected in drinking water and any trace amounts of endrin that might be encountered in
raw drinking water supplies will likely be removed in the treatment systems used by most communities.
In 1966 and 1967, when the use of endrin was not restricted, endrin was detected in 5 of 67 raw water
samples from the Mississippi and Missouri Rivers (Schafer et al. 1969). At a later time when endrin use
was substantially restricted, an Iowa study of 33 community water supplies using surface water found no
detectable concentrations of endrin in the distribution systems (Wnuk et al. 1987). In an extensive water
quality monitoring program conducted by the California Department of Health Services, endrin was
detected (detection limit not specified) in only 2 of 5,109 public drinking water sources sampled from

ENDRIN 100
1984 to 1992, at mean and maximum concentrations of 0.06 and 0.10 ppb, respectively (Storm 1994).
Concentrations did not exceed the maximum concentration level of 0.2 ppb. In another study, endrin was
not detected (detection limit not specified) in 32 samples each of raw water and highly treated reclaimed
waste water undergoing evaluation as a possible supplement to raw water sources in San Diego,
California (De Peyster et al. 1993).
Detections of endrin in groundwater are also rare except from wells near hazardous waste sites. The EPA
Pesticides in Groundwater Data Base (EPA 1989) contains groundwater data collected with good quality
assurance/quality control (QA/QC) provisions from areas with significant agricultural land uses as well as
from urban areas. Analysis of these data indicated there were only two wells with detectable levels of
endrin within the entire United States. A detection occurred in a well in California (concentration not
reported) where point source problems or spills were deemed the likely sources. Endrin contamination
found in an Illinois well at an average concentration of 0.02 ppb was considered likely to have resulted
from ordinary agricultural uses. In a groundwater contamination study of California’s 58 counties, in
which over 50 pesticides were evaluated from both point and nonpoint sources, endrin was detected in
only one sample (Cohen 1986). In another study, endrin was detected at 0.9% of 178 Comprehensive
Environmental Response, Compensation, and Liability Act (CERCLA) sites and 1.3% of 156 Resource
Conservation and Recovery Act (RCRA) sites sampled; however, endrin concentrations were not reported
(Plumb 1987).
No information was found in the available literature on levels of endrin aldehyde or endrin ketone in
surface or groundwater.
5.5.3 Sediment and Soil
Very little recent information on levels of endrin in soils was found in the available literature. From the
available data it appears that, in general, endrin was found infrequently and at relatively low levels in both
urban and cropland soils in the United States. Endrin was detected in only 10 of 1,483 cropland soil
samples in 1972 at concentrations up to 2.13 ppm (detection limit of 0.01 ppm) (Carey et al. 1979).
These studies were part of the National Soils Monitoring Program carried out by EPA and the U.S.
Department of Agriculture (USDA) under the National Pesticide Monitoring Program, which covered a
total of 1,533 sampling sites in 37 states. Endrin detections were documented in the following states:
Alabama, Arkansas, Georgia, Illinois, Louisiana, Nebraska, New York, North Carolina, and South
Dakota, as well as at sites from one or more of the mid-Atlantic states of Delaware, Maryland, and New

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Jersey. Endrin was also detected at a level of 0.017 ppm at a single site in California in a study that
targeted rice-growing cropland soils in Arkansas, California, Louisiana, Mississippi, and Texas (Carey et
al. 1980). Endrin was not detected in urban soils from 13 of 14 U.S. cities included in a 1970 study of
pesticide residues in urban soils (25–30 soil sampling sites were used for each of the urban areas) (Carey
et al. 1976). The only detection was at a single site near Memphis, Tennessee, where the Velsicol
Chemical Company (which produced endrin at that time) is located. The reported concentration for this
site was 0.07 ppm; the mean concentration for all 28 Memphis sites was <0.01 ppm.
Relatively little literature was identified concerning the analysis of endrin in aquatic sediments. The
available data indicate that, historically, sediment concentrations of endrin have been very low. In a
recent study of sediment contaminants in Casco Bay, Maine, endrin was found at concentrations near or
below the method detection limit (<0.25 ppb) (Kennicutt et al. 1994). In the National Surface Water
Monitoring Program conducted from 1976 to 1980, endrin was detected in 1.3% of the sediment samples
analyzed (detection limit not reported), with a maximum concentration of 2.9 ppb (Carey and Kutz 1985).
An analysis of EPA STORET data indicated that endrin was detected in 24% of the 1,802 sediment
records listing endrin as a parameter code. The median endrin concentration for all records was
0.001 ppb (Staples et al. 1985). A similar analysis of STORET data indicated that endrin aldehyde was
not found in any of 251 samples of sediment (Staples et al. 1985). In a study by Ford and Hill (1991) to
evaluate organochlorine pesticide residues in sediments and aquatic animals in the vicinity of the Yazoo
National Wildlife Refuge in the Mississippi Delta, a region that has experienced very high usage of
pesticide agents, detectable levels of endrin were not found in sediments (detection limit 0.01 ppm
[10 ppb]). Similarly, endrin was not detected in sediment or pore water samples (detection limits 0.49
and 0.01 ppm [490 and 10 ppb], respectively) from 18 mosquito control impoundments in St. Lucie
County, Florida, where organochlorine pesticides had been heavily used through the early 1960s
(Parkinson et al. 1993).
There is a potential for endrin to be present in soils and sediments at hazardous waste sites. Endrin was
not detected (detection limit 0.01 ppm [10 ppb] wet weight), however, in soils derived from dredged
materials at nine confined disposal facilities bordering the Great Lakes (Beyer and Stafford 1993).
No information was found in the available literature on levels of endrin aldehyde in soil or endrin ketone
in sediment or soil.

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5.5.4 Other Media
Endrin has been found in many foods, but current levels appear to be very low and not of concern for
human health. The FDA has concluded that endrin is no longer present in the environment to the extent
that it may be contaminating food or feed at levels of regulatory concern (USDA 1995). An FDA survey
of pesticide residues in samples of domestic and imported food and feed commodities from Fiscal Year
(FY) 1982 to 1986 lists endrin levels for specific food items up to 0.50 ppm (500 ppb) (Hundley et al.
1988). This study was conducted by surveillance sampling with follow-up compliance sampling for
sources of foodstuffs where the concentrations in surveillance samples violated EPA tolerance levels. In
surveillance sampling, endrin was detected in 0.05% (3 of 6,391 samples) and 1.5% (183 of
12,044 samples) of domestic and imported foods, respectively. The incidence of violative surveillance
samples (endrin residues ≥0.05 ppm [50 ppb]) was higher for imported foods (0.1%; 12 violations) than
for food items from domestic sources (0.02%; 1 violation). In follow-up compliance monitoring of
1,239 samples of imported foods, endrin was found in 11 samples (0.9%); 2 of these samples (0.2%) were
violative. In imported foods, endrin was detected in mung beans, cucumbers, pickling cucumbers,
cantaloupe, acorn squash, cabocha squash, Italian squash, summer squash, and yellow squash (Hundley et
al. 1988). No follow-up compliance monitoring of domestic samples for endrin residues was performed.
In another study of pesticide residues in food conducted in 10 states between 1988 and 1989, endrin was
not detected in any of the 13,980 samples analyzed in 1988. In 1989, the detection frequencies for endrin
and endrin ketone were 0.084 and 0.007%, respectively, for the 13,085 samples analyzed (Minyard and
Roberts 1991). In a Canadian study, reported concentrations of endrin in composite samples of fresh root
vegetables, fruit, leafy and other above-ground vegetables, and cows’ milk ranged from 0.27 to 0.37 ppb;
endrin was not detected in composite samples of fresh meat and eggs (detection limit 0.01 ppb) (Davies
1988). Endrin was detected each year in regulatory monitoring of domestic and imported foods
conducted by the FDA from 1989 to 1994 as part of its Pesticide Residue Monitoring Program (FDA
1990, 1991, 1992, 1993, 1994, 1995). Concentrations were not reported; however, <1% of the
surveillance samples had any pesticide residue levels that were above established tolerances. Endrin was
also detected in the FDA Total Diet Studies in 1987, 1988, 1989, and 1991, but not in 1990 (FDA 1988,
1989, 1990, 1991, 1992). Reports of 1992–1994 FDA Total Diet Studies did not indicate whether endrin
was detected in those years (FDA 1993, 1994, 1995). In the years in which endrin was detected in the
FDA Total Diet Studies, it was not among the most frequently detected pesticides. Concentrations of
endrin found in the FDA Total Diet studies were not reported. However, in an overall summary for the
5-year period 1986–1991, average dietary intakes of endrin for eight age/sex groups (6–11-month-old

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infants, 2-year-old children, 14–16-year-old males and females, 25–30-year-old males and females, and
60–65-year-old males and females) were all estimated to be <0.000l µg/kg body weight/day, <0.03% of
the EPA reference dose (RfD) of 0.3 µg/kg body weight/day (FDA 1993). A food basket survey
patterned after the FDA approach that was conducted in San Antonio, Texas did not find detectable
concentrations of endrin (detection limit 0.050 ppm [50 ppb]) in 6,970 produce items (Schattenberg and
Hsu 1992).
Overall, in 234 ready-to-eat foods tested 37 times each as part of the FDA Total Diet Studies from 1982
to 1991, endrin was found only 26 times at an average concentration of 0.0027 (µg /g (2.7 ppb) in nine
different foods: broccoli, cantaloupe, collards, cucumbers, onion rings, dill pickles, pumpkin pie, summer
squash, and winter squash (KAN-DO Office and Pesticides Team 1995). Concentrations ranged from
0.0011 µg/g (1.1 ppb) (broccoli) to 0.0041 µg/g (4.1 ppb) (summer squash). In a summary of 1985–1991
FDA pesticide residue findings, endrin was not reported in >10,000 surveillance samples of domestic and
imported foods that may be eaten by infants or children, or in >4,000 analyses of Total Diet Study foods
eaten by infants and children (Yess et al. 1993).
Other studies further indicate that the occurrence of endrin in the U.S. food supply is very low. In a
1990–1991 FDA survey of pesticide residues in milk representing most of the U.S. supply consumed in
metropolitan areas, endrin was detected at trace levels (0.0005–0.001 ppm [0.5–1.0 ppb]) in only 2 of
806 composite samples (one sample each from Atlanta, Georgia and Dover, Delaware) (Trotter and
Dickerson 1993). In another statistically based FDA study in 1992–1993, endrin was not found as a
violative residue in any of 710 domestic or 949 imported pear samples (Roy et al. 1995). Endrin was not
reported among the pesticides detected in a 1994 FDA survey of pesticide levels in 160 samples of
catfish, crayfish, shrimp, trout, salmon, oysters, and various other species from important aquaculture
areas of the United States (FDA 1995). Comparable results were found in similar studies conducted by
the FDA in 1990–1993 (FDA 1995).
Because of the persistence of endrin in the environment and its potential to bioconcentrate significantly in
aquatic organisms, there has been continued concern over the levels of endrin in fish and shellfish. This
concern, however, appears to be limited primarily to specific sites where endrin was used heavily in
agriculture or was discharged by industrial plants. In 1963, at the height of agricultural endrin use, endrin
levels in catfish poisoned by endrin exceeded 4 ppm (4,000 ppb) during a fish kill (Mount and Putnicki
1966). Endrin was detected in two species of commercial Penaeus shrimp collected at 21 of 31 stations in
the Calcasieu River Estuary in Louisiana, a Gulf Coast estuary receiving both industrial discharges and

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urban and agricultural runoff (Murray and Beck 1990). The maximum, mean, and median concentrations
of endrin reported were 9.47, 1.07, and 0.25 ppm (9,470, 1,070, and 250 ppb), respectively. Several other
national studies, however, indicated that contaminated fish or shellfish currently are not a likely source of
potentially high human exposure to endrin. In the National Contaminant Biomonitoring Program,
maximum endrin concentrations in whole fish from around the United States for the periods 1976–1777,
1978–1979, 1980–1981, and 1984 were 0.40, 0.11, 0.30, and 0.22 ppm (400, 110, 300, and 220 ppb),
respectively. Corresponding geometric mean concentrations were ≤0.01 ppm (10 ppb) (Schmitt et al.
1985, 1990). The percentage of stations where detectable endrin residues were present also showed a
relatively steady decline from 47.2% in 1976–1977 to 28% in 1984. The maximum concentration of
0.22 ppm (220 ppb) in 1984 was recorded near Memphis in the vicinity of the Velsicol Chemical
Company. In portions of the Mississippi Delta within or bordering the Yazoo National Wildlife Refuge,
endrin was found at the 0.01 ppm (10 ppb) detection limit in whole-body tissue samples from such rough
fish as carp, smallmouth buffalo, bowfin, and spotted gar collected in 1988 (Ford and Hill 1991). In the
1986 National Study of Chemical Residues in Fish conducted by the EPA, endrin was detected in fish
tissue samples at 11% of the 362 sites surveyed. The maximum, mean, and median concentrations of
endrin reported were 0.162 ppm, 0.002 ppm, and not detected (<0.0025 ppm) (162, 2, and <2.5 ppb),
respectively (EPA 1992b).
Endrin concentrations also have been monitored in several studies in the Great Lakes region. Endrin was
detected in eight fish species from three Great Lakes-influenced rivers in Michigan at average
concentrations ranging from not detected (detection limit not specified) to 8.03 ppb wet weight (Giesy et
al. 1994). Average concentrations exceeded 1.5 ppb for samples from only 2 of 23 species/site
combinations and were <0.5 ppb for samples from 17 of 23 species/site combinations. Endrin was
detected (detection limit 0.02 ppm [20 ppb] wet weight) in 5 of 10 samples of lake trout (mean
concentration 0.03+0.01 ppm [30+10 ppb]) collected in Lake Michigan in 1982 (Miller 1993). It was not
detected in 10 samples of lake trout collected in Lake Superior or in 18 samples of chinook salmon
collected in Lake Michigan. Endrin was not detected (detection limit 2 ng/g [ppb] wet weight) in
16 skinless fillets of both rainbow trout (Oncorhyncus mykiss) and black bullheads (Ameiurus melas)
cultivated for 6 and 3.5 months, respectively, in Lake Ontario waters (Buttner et al. 1995). Endrin also
was not detected (detection limit not specified) in samples of whole Zebra mussels (Dreissena
polymorpha) from populations infesting two power-generating stations in Lake Erie (Doherty et al. 1993).
Endrin has been detected in several marine fish species in regional or state monitoring studies. From
1990 to 1993, endrin was found in 40 of 47 whole or fillet samples of red drum (Sciaenops ocellatus) at

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two of four sites along the South Carolina coast, at mean concentrations of 5.61+8.94 and 0.65+3.67 ppb
wet weight (Mathews 1994). In this same study, endrin was found in 33 of 74 flounder (Paralichthys
lethostigma) samples and in 19 of 58 seatrout (Cynoscion nebulosus) samples at only one coastal site, at
mean concentrations of 0.14+0.81 and 2.68+11.13 ppb, respectively. Endrin was detected in all of
10 liver tissue samples from cod (Gadus morhua) in the Northwest Atlantic at a mean concentration of
9 ppb (range, 5–19 ppb), but not in muscle or ovary samples (Hellou et al. 1993).
There may be a potential for contamination of fish and wildlife in the vicinity of hazardous waste sites.
5.6 GENERAL POPULATION EXPOSURE
Endrin is no longer registered for use in the United States. Consequently, the current potential for
exposure of the general population to endrin appears to be very limited and will likely continue to
diminish even more over time. Members of the general population may be exposed to very low levels of
endrin through ingestion of contaminated foodstuffs, particularly those that are imported from areas
where endrin is still being used. However, FDA concluded that endrin is no longer present enough in the
environment to contaminate food or feed at levels of regulatory concern (USDA 1995). Several studies
indicate that human exposures are far below the levels of concern for human health. Based on results of
FDA Total Diet Studies conducted from 1978 to 1982, estimated average dietary intakes were
<0.001 µg/kg (ppb) body weight/day for infants and toddlers for all 5 years (Gartrell et al. 1986).
However, actual intakes must have been lower than these estimates because the reported average dietary
intakes were based on the mean concentration of the positive samples only. A report summarizing the
FDA Total Diet Studies from April 1982 to April 1984 indicated an estimated daily intake for 6–
11-month-old infants of 0.0003 µg/kg (ppb)body weight/day for that period, with estimated daily intakes
for 14–16-year-old males and 60–65-year-old females essentially zero (Gunderson 1988). Endrin intakes,
in µg/kg (ppb) body weight/day, estimated from the Total Diet Study analyses were <0.0001, <0.0001,
and 0.0001 in FY 1989 for 6–11-month-old infants, 14–16-year-old males, and 60–65-year-old females,
respectively (FDA 1990), and <0.000l in FY 1991 for all age categories (FDA 1992). Estimated endrin
intakes were not reported for FY 1990 (FDA 1991). In an overall summary of FDA Total Diet Studies
for the 5-year period 1986–1991, average dietary intakes of endrin for eight age/sex groups (6–11-month-
old infants, 2-year-old children, 14–16-year-old males and females, 25–30-year-old males and females,
and 60–65-year-old males and females) were all estimated to be <0.0001 µg/kg (ppb) body weight per
day, <0.03% of the EPA oral RfD of 0.3 µg/kg (ppb) body weight per day (FDA 1993). In Canada,

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where endrin was registered for use from 1954 to 1990, a dietary intake study estimated the adult annual
intake of endrin at approximately 32 µg (0.001 µg/kg [ppb] body weight/day) (Davies 1988).
The National Health and Nutrition Examination Survey (NHANES) uses biomonitoring to provide
estimates of exposure to the civilian U.S. population. Chemicals and their metabolites are measured in
subsets of participants aged 6–59 years old, meant to be a representative sample of the general U.S.
population. Serum endrin values were surveyed during the years 2001–2004; endrin was pooled with
other organochlorines in subsequent NHANES surveys (CDC 2018). As shown in Table 5-4, endrin was
below the limit of detection (LOD) in most samples. The LODs for survey years 2001–2002 and 2003–
2004 are 5.09 and 7.8 ng/g lipid, respectively. The analytical method used for the analysis was gas
chromatography with high-resolution mass spectrometry.
Although endrin bioaccumulates significantly in aquatic organisms (ASTER 1995; EPA 1980a; Metcalf
et al. 1973), studies indicate that endrin levels in fish and shellfish in the United States are not of concern
for human health (EPA 1992a; Ford and Hill 1991; Murray and Beck 1990; Schmitt et al. 1985, 1990).
Dietary exposures to endrin from domestic fish were estimated from 1984 to 1988 FDA surveillance data
to be 1.7x10-5 µg/kg (ppb) body weight/day (Ahmed et al. 1993). As of 1995, there were no fish
consumption advisories for endrin in effect in the United States (EPA 1995b).
The most recent National Human Adipose Tissue Survey did not detect endrin in adipose tissues from the
general U.S. population (Stanley 1986). Endrin also was not detected in adipose breast tissue from breast
cancer patients (n=5) or controls (n=5) in the United States (Djordjevic et al. 1994). A 1984 study based
on autopsied adipose tissue from 141 cadavers from six Canadian Great Lakes municipalities showed no
detectable concentrations of endrin (detection limit 2.4 ppb) (Williams et al. 1988). In a 1990–1991
survey, only very low levels of endrin (average concentration 3.27 ng/g (ppb); range 0.23–8.56 ng/g [ppb]
lipid) were found in adipose tissue samples from 3 of 41 residents of British Columbia, Canada, where
endrin was registered for use from 1954 to 1990 (Teshke et al. 1993).
Endrin has been detected in the milk of lactating women living outside the United States; however, no
data from the United States could be located. Data from other countries indicate that there is some
correlation between the levels of endrin used in, or transported to, an area and concentrations found in
breast milk. Endrin was not detected in breast milk samples from a remote area of Papua, New Guinea
(Spicer and Kereu 1993). In a recent investigation of Inuit exposure to organochlorine pesticides through

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Table 5-4. Serum Endrin Levels (Lipid-Adjusted) in the NHANES U.S. Population
Selected percentiles (95% confidence interval) (ng/g

Geometric mean (95% CI) lipid) Sample
Survey yearsa (ng/g lipid) 50th
75th
90 th
95th size
Total 2001–2002 Not calculatedb <LOD <LOD <LOD 5.10 (<LOD–5.40) 2,187
2003–2004 Not calculated <LOD <LOD <LOD LOD 1,825
Age group
12–19 years 2001–2002 Not calculated <LOD <LOD 5.20 (<LOD–5.50) 5.60 (5.40–5.70) 730
2003–2004 Not calculated <LOD <LOD <LOD <LOD 539
≥20 years 2001–2002 Not calculated <LOD <LOD <LOD <LOD 1,457
2003–2004 Not calculated <LOD <LOD <LOD <LOD 1,286
Sex
Males 2001–2002 Not calculated <LOD <LOD <LOD 5.20 (<LOD–5.40) 1,022
Females 2001–2002 Not calculated <LOD <LOD <LOD <LOD 1,165
Race/ethnicity
Mexican Americans 2001–2002 Not calculated <LOD <LOD <LOD 5.30 (<LOD–6.50) 547
Non-Hispanic blacks 2001–2002 Not calculated <LOD <LOD <LOD 5.40 (<LOD–6.30) 487
Non-Hispanic whites 2001–2002 Not calculated <LOD <LOD <LOD 5.10 (<LOD–5.40) 1,000
aThe limit of detection for survey years 2001–2002 and 2003–2004 were 5.09 and 7.8 ng/g lipid, respectively. Serum endrin data are not available from NHANES
after 2004 because endrin was pooled with other organochlorines in subsequent analyses.
bNot calculated: proportion of results below LOD was too high to provide valid results.
LOD = limit of detection; NHANES = National Health and Nutrition Examination Survey
Source: CDC 2018

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the aquatic food chain in Arctic Quebec, endrin was detected in only 1 of 107 breast milk samples from
Inuit women, at a concentration of <8 ng/g (ppb) in milk fat, and in none of 50 samples from southern
Quebec Caucasian women (Dewailly et al. 1993). In France, where endrin has not been used for over
20 years, endrin was detected in 8 of 20 human milk samples collected 20–90 days after parturition.
Concentrations ranged from 0.02 to 0.84 ppm (20–840 ppb) in milk fat, with a mean concentration of
0.06 ppm (60 ppb) (Bordet et al. 1993). Higher levels of endrin were found in human milk in a study
conducted in Jordan, where endrin was widely used over the previous 40 years (Alawi et al. 1992). In this
study, endrin was detected in samples from 3 of 15 donors at concentrations ranging from 0.26 to
6.24 ppm (260–6,240 ppb) in milk fat. The median and maximum daily intakes of endrin for breastfed
infants were estimated to be 1.55 and 12.70 mg/kg (ppm) (1,550 and 12,700 ppb) body weight,
respectively. The relevance of these findings to the U.S. population is unclear.
Although all uses of endrin in the United States were canceled by 1991 (Bishop 1984, 1985, 1986; EPA
1993e; USDA 1995), occupational exposures to endrin, endrin aldehyde, and endrin ketone may occur
among workers involved in the handling and treatment of materials at hazardous waste sites, and among
agricultural workers at sites formerly treated with endrin. No information was found in the available
literature on current occupational exposures. In the past, exposures of agricultural workers were
significant. Seasonal agricultural workers dusting potatoes with 1% endrin dust were calculated to be
exposed to a dermal dose of 2.0 mg/kg (ppm) body weight/day and an inhalation dose of 0.04 mg/kg
(ppm) body weight/day at a time when agricultural use of endrin was near its peak (Wolfe et al. 1963).
Occupational exposure to endrin was not evaluated during the National Occupational Exposure Survey
(NOES) conducted from 1981 to 1983 or its predecessor, the National Occupational Hazard Survey
(NOHS) conducted from 1972 to 1974. The surveys conducted by the National Institute for Occupational
Safety and Health (NIOSH) were designed to provide data necessary to describe potential exposure agents
and profile health and safety programs in United States workplaces. According to the Occupational
Safety and Health Administration (OSHA) (2016a, 2016b, 2017), the 8-hour TWA permissible exposure
level (PEL) for endrin is 0.1 mg/m3. NIOSH (2016) also advises that the recommended exposure limit for
occupational exposure to endrin not exceed 0.1 mg/m3 for a 10-hour TWA workday. In addition, the
American Conference of Government Industrial Hygienists (ACGIH) recommended threshold limit value
(TLV-TWA) for occupational exposure is 0.1 mg/m3 (ACGIH 2001).
No information could be found in the available literature on general population or occupational exposures
to endrin aldehyde or endrin ketone.

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5.7 POPULATIONS WITH POTENTIALLY HIGH EXPOSURES
A susceptible population will exhibit a different or more enhanced response than most persons exposed to
the same level of endrin in the environment. Reasons include genetic make-up, developmental stage, age,
health and nutritional status (including dietary habits that may increase susceptibility, such as inconsistent
diets or nutritional deficiencies), and substance exposure history (including smoking). These parameters
result in decreased function of the detoxification and excretory processes (mainly hepatic, renal, and
respiratory) or the pre-existing compromised function of target organs (including effects or clearance
rates and any resulting end-product metabolites). For these reasons, the elderly with declining organ
function and the youngest of the population with immature and developing organs are expected to be
generally more vulnerable to toxic substances than healthy adults.
Persons with a history of convulsive disorders would be expected to be at increased risk from exposure to
endrin. Children may be more sensitive than adults to the acute toxic effects of endrin. In an endrin
poisoning episode in Pakistan, children 1–9 years old represented about 70% of the cases of convulsions
(Rowley et al. 1987). The causative factor responsible for the outbreak was not identified, however, and
the age distribution of cases could be explained by age-specific exposure situations. In general, following
oral administration, female animals appear to be more susceptible to endrin toxicity than males (Gaines
1960; Treon et al. 1955). The difference may be due to the more rapid excretion of endrin by male versus
female rats (Hutson et al. 1975; Klevay 1971; Korte et al. 1970). A sex-related difference in toxicity was
not apparent following dermal exposure (Gaines 1960, 1969). No sex-based differences in endrin-related
human toxicity have been documented. For example, an equal number of male and female patients were
affected in the endrin poisoning episode in Pakistan (Rowley et al. 1987).
Endrin has not been registered for use in the United States since voluntary cancellation of its final use as
an avicide on bird perches in 1991 (USDA 1995). All other uses of endrin were voluntarily canceled by
1986 (Bishop 1984, 1985, 1986; EPA 1993e; USDA 1995). Therefore, there are currently no population
groups exposed to high levels of endrin associated with its application as a pesticide agent. Populations
exposed to higher than background concentrations of endrin, endrin aldehyde, or endrin ketone include
those living near hazardous waste sites where these compounds are present. Skin contact with or
ingestion of endrin-contaminated soil may be an important source of exposure for children living near
such hazardous waste sites. In addition, groundwater may be a source of exposure to endrin for adults
and children if they consume drinking water from contaminated wells.

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CHAPTER 6. ADEQUACY OF THE DATABASE
Section 104(i)(5) of CERCLA, as amended, directs the Administrator of ATSDR (in consultation with the
Administrator of EPA and agencies and programs of the Public Health Service) to assess whether
adequate information on the health effects of endrin is available. Where adequate information is not
available, ATSDR, in conjunction with NTP, is required to assure the initiation of a program of research
designed to determine the adverse health effects (and techniques for developing methods to determine
such health effects) of endrin.
Data needs are defined as substance-specific informational needs that, if met, would reduce the
uncertainties of human health risk assessment. This definition should not be interpreted to mean that all
data needs discussed in this section must be filled. In the future, the identified data needs will be
evaluated and prioritized, and a substance-specific research agenda will be proposed.
6.1 Information on Health Effects
Studies evaluating the health effects of inhalation, oral, and dermal exposure of humans and animals to
endrin that are discussed in Chapter 2 are summarized in Figure 6-1. The purpose of this figure is to
illustrate the information concerning the health effects of endrin. The number of human and animal
studies examining each endpoint is indicated regardless of whether an effect was found and the quality of
the study or studies.
As illustrated in Figure 6-1, most of the data on the toxicity of endrin come from oral studies in laboratory
animals. The most examined endpoints were neurological, hepatic, renal, body weight, and
developmental effects. The available human studies include occupational health surveys, population-
based studies, and case series predominantly focused on neurological effects and cancer. However, more
recent human studies evaluated potential endocrine, reproductive, and developmental effects. For the
purposes of Figure 6-1, all occupational studies were classified as inhalation studies and all population-
based studies were classified as oral studies; however, it is acknowledged that humans were likely
exposed via multiple exposure routes in both occupational and environmental settings. The laboratory
animal inhalation and dermal toxicity database consists of a small number studies evaluating limited
endpoints. Only one study (Young and Mehendale 1986) was found on the health effects of endrin
aldehyde or endrin ketone in animals following oral exposure; all other animal studies in Figure 6-1
evaluate endrin.

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6. ADEQUACY OF THE DATABASE
Figure 6-1. Summary of Existing Health Effects Studies on Endrin By Route and
Endpoint*
Most studies examined the potential hepatic and neurological effects of endrin
The majority of the studies examined oral exposure in animals (versus humans)
Includes studies discussed in Chapter 2. A total of 93 studies (including those finding no effect) have examined
toxicity; most animal studies examined multiple endpoints. All occupational studies were classified as inhalation
studies and all population-based studies were classified as oral studies to avoid double counting these studies;
however, it is acknowledged that humans were likely exposed via multiple exposure routes in both occupational and
environmental settings

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6.2 Identification of Data Needs
Missing information in Figure 6-1 should not be interpreted as a “data need.” A data need, as defined in
ATSDR’s Decision Guide for Identifying Substance-Specific Data Needs Related to Toxicological
Profiles (ATSDR 1989), is substance-specific information necessary to conduct comprehensive public
health assessments. Generally, ATSDR defines a data gap more broadly as any substance-specific
information missing from the scientific literature.
Acute-Duration MRLs. Additional well-designed, low-dose acute studies designed to evaluate a wide-
array of neurological endpoints, including neurobehavior, could potentially identify a NOAEL for
neurological effects following acute exposure and decrease the uncertainty in the provisional acute oral
MRL. The inhalation database is inadequate to derive an acute-duration inhalation MRL; available
human studies do not provide exposure data and the animal database is limited to a single study reporting
lethality and histological alterations in the brain of a single cat (Ressang et al. 1959). Well-designed
acute studies evaluating a comprehensive set of endpoints, including neurotoxicity, could potentially
identify a point of departure (POD) to use as the basis for an acute inhalation MRL. The oral database is
adequate to derive a provisional acute-duration oral MRL based on neurobehavioral changes in rats.
Intermediate-Duration MRLs. Well-designed, intermediate-duration inhalation and oral studies

designed to evaluate a wide array of endpoints at low exposure levels, particularly neurological endpoints,
could potentially identify an appropriate POD to use as the basis for intermediate-duration MRLs. The
inhalation database is not adequate to derive an intermediate-duration inhalation MRL; there are no
available human studies and the animal database is limited to a single study evaluating mice and rabbits
exposed to lethal concentrations (Treon et al. 1955). The oral database is also inadequate to derive an
intermediate-duration oral MRL due to inadequate low-dose information; however, the provisional acute-
duration oral MRL was adopted as the provisional intermediate-duration oral MRL.
Chronic-Duration MRLs. Additional well-designed, low-dose chronic studies designed to evaluate a

wide-array of neurological endpoints, including neurobehavior, could decreased the uncertainty in the
chronic oral MRL. The inhalation database is inadequate to derive a chronic-duration inhalation MRL;
available human studies do not provide exposure data and there are no animal studies. Low-exposure
inhalation studies designed to identify a NOAEL for neurological effects could potentially identify a POD
to use as the basis for a chronic-duration inhalation MRL. The oral database is adequate to derive a
chronic-duration oral MRL.

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Health Effects.
Neurotoxicity. While overt neurological effects are well characterized following oral
exposures and, to a lesser extent, inhalation and dermal exposures, additional studies specifically
to evaluate a wide array of neurological endpoints, including neurobehavior, would be helpful to
establish dose-response relationships. Studies in humans indicate that endrin causes changes in
the nervous system after occupational and oral exposure. Clinical symptoms including twitching
and jerking of muscles, seizures, dizziness, and mental confusion within 2 hours following
occupational exposure. Studies in animals confirm the neurotoxic potential of endrin.
Hepatic Toxicity. Additional low-exposure studies may better define the dose-response
relationships. There is limited evidence of changes in liver function in endrin-exposed workers.
Animal studies confirm that hepatotoxicity occurs following exposure at or near lethal doses.
Hepatotoxicity has been observed following chronic exposure to sublethal doses.
Renal Toxicity. Additional low-exposure studies may better define the dose-response
relationships. There are no data in humans regarding changes in renal function in endrin-exposed
individuals. Inhalation, oral, and dermal exposure at or near lethal levels of endrin caused diffuse
degenerative lesions in the kidneys of various species. There is limited evidence of renal effects
(cloudy swelling of tubule epithelial cells) at nonlethal doses from one chronic study in rats
(Deichmann et al. 1970); however, this finding was not confirmed in rats or mice at sublethal
chronic doses in an NCI (1978) bioassay.
Respiratory Toxicity. Additional epidemiological studies and low-exposure animal studies in

several species may better define potential respiratory effects and inform the dose-response
relationships. No clear associations have been observed between altered respiratory function or
disease and occupational endrin exposure in humans; however, human data are limited to two
studies. In animals, most respiratory tract effects were associated with lethal exposure levels, and
were attributed to widespread systemic failure. However, one chronic rat study reported focal
hemorrhage and congestion of the lungs at sublethal levels.
Cardiovascular Toxicity. Additional epidemiological studies and low-exposure animal

studies in several species may better define potential cardiac effects and inform the dose-response

ENDRIN 114
relationships. No clear associations have been observed between environmental or occupational

endrin exposure in humans; however, available human data are extremely limited. In dogs,
diffuse degenerative lesions have been reported at lethal doses and elevated heart weight has been
reported at sublethal doses. These findings have not been observed in other animal species.
Endocrine Toxicity. Additional epidemiological studies and low-exposure animal studies in

several species may better define potential endocrine effects and inform the dose-response
relationships. No clear associations have been observed between environmental exposure to
endrin and endocrine effects in humans. In animals, chronic exposure to sublethal dietary doses
caused thyroid hyperplasia and pituitary cysts in rats, but not mice.
Immunotoxicity. In vivo studies designed specifically to assess immune function (inhalation,

oral, and dermal exposure routes), as well as additional in vitro testing involving humoral
mediated immunity and nonspecific immunity, could be useful in assessing the immunotoxic
potential of endrin. No in vivo studies evaluating immune function are available in humans or
animals following exposure to endrin after inhalation, oral, or dermal exposure. Results of in
vitro assays evaluating inhibition of lymphocyte responses and neutrophilic chemotaxis were
negative. Animal studies are limited to oral studies reporting inconsistent organ weight changes
in immune organs; the only study evaluating immune organ histopathology did not observe any
histopathological lesions after chronic exposure.
Reproductive Toxicity. Additional, well-designed reproductive assays evaluating various

species and several dose levels via the oral route (and other routes as well) would be useful in
assessing the potential reproductive toxicity of endrin. No clear associations have been observed
between environmental endrin exposure and preterm labor or birth outcomes in humans;
however, there is limited evidence of a potential association between delayed female physical and
sexual development in adolescents living in a highly contaminated region in Kazakhstan.
Additional well-designed epidemiological studies with appropriate statistical power and control
for confounding variables would be useful to further evaluate this potential association. No
studies are available on the reproductive effects of endrin in animals after inhalation or dermal
exposure. Reproductive toxicity data in animals are limited to two 1-generation studies, one in
mice limited to a single dose level (Good and Ware 1969) and one in dogs with several
experimental flaws (Kettering 1971), and a low-dose 3-generation study in rats (Eisenlord et al.
1968). Only the mouse study indicated potential reproductive effects (decreased litter size).

ENDRIN 115
Developmental Toxicity. Additional low-exposure studies could determine if any additional

developmental effects occur at oral doses below maternal toxicity or following inhalation or
dermal exposure. Conducting these studies in multiple species could be helpful in identifying
potential species differences. Limited evidence in humans indicate that endrin is not associated
with adverse birth outcomes or impaired male reproductive development; however, one study
reported an association between endrin exposure and cord blood thyroid hormone levels.
Offspring of mice and hamsters exposed to endrin during gestation showed statistically
significant increases in the incidence of fused ribs, cleft palate, exencephaly, and
meningoencephaloceles at maternally toxic doses. In rats, only delayed ossification was observed
at maternally toxic doses. However, perinatal studies in rats suggest altered neurobehavior in
offspring at doses below those associated with maternal toxicity.
Epidemiology and Human Dosimetry Studies. Additional quantitative exposure data obtained
from individuals occupationally exposed to low levels of endrin would be useful in evaluating potential
risk to people living near hazardous waste sites. There are reports on the adverse effects of endrin in
humans. These reports involve acute exposures in people who ingested endrin-contaminated food,
occupational surveys and case reports, and population-based studies. Most studies have poor control for
confounding variables, particularly exposure to other organochlorine pesticides, and/or have low
statistical power. Despite limitations, existing studies identify the nervous system as a major target
associated with exposure to endrin. However, reliable quantitative exposure levels that lead to these
effects are lacking.
Biomarkers of Exposure and Effect. Measurement of endrin and its metabolites can be useful
indicators of exposure. Since endrin is cleared from the blood rapidly, such measurements are suitable
only for recent exposures. Additional studies could potentially determine the usefulness of metabolites in
urine as biomarkers of exposure in humans. Changes in the nervous system appear to be the main effect
associated with human exposure to endrin. Effects on the nervous system can be monitored in exposed
individuals by measuring the incidence of signs and symptoms such as myoclonic jerking, seizures,
convulsions, dizziness, and mental confusion. Because these effects also occur following exposure to
other organochlorine pesticides and drugs, the development of more specific biomarkers of endrin
exposure would be useful for studying potential endrin-related adverse health effects.

ENDRIN 116
Absorption, Distribution, Metabolism, and Excretion. Additional studies are needed to

determine absorption rates following exposure by all routes. There are limited data on the absorption of
endrin in humans and animals. Limited studies provide qualitative evidence that endrin is absorbed
following inhalation, oral, and dermal exposures; however, no information is available on the rate or
extent of absorption that occurs by any of these routes.
Data are sparse on the distribution of endrin. Limited data in humans indicate that significant amounts of
endrin residues are found in adipose tissue of people acutely exposed to high levels, but not typically in
the general population. However, endrin has been detected in breast milk and placental tissues. Low
levels of endrin are found in the liver, kidneys, and brain in people exposed to endrin or endrin-
contaminated food. The time of sample collection is critical since endrin residues in tissues decline
rapidly after exposure has ceased.
Additional studies in different species, as well as inhalation and dermal exposure studies, would be
helpful. No studies were found regarding the metabolism of endrin in humans, excretion patterns in
workers show metabolites similar to those identified in animal studies. Metabolism following oral
exposure in animals has been fairly well characterized and shows some species differences.
Additional studies on the excretion of endrin and its metabolites via the dermal route would be useful
since differences in urinary metabolite profiles have been observed following exposure to endrin by other
routes. Excretion patterns following oral and inhalation exposure have been fairly well characterized.
Comparative Toxicokinetics. Additional studies using all three potential routes of human exposure
would be useful in understanding differences in species and in determining which animal species is the
most appropriate model for human exposure. There are limited data on the kinetics of endrin in humans.
Studies in animals suggest that metabolism and urinary metabolite profiles vary among species.
Children’s Susceptibility. Developmental effects have not been evaluated in animals following
inhalation or dermal exposure. Studies in young animals and/or epidemiological data for children would
be useful to address these data gaps. Data are inadequate to determine if children are more susceptible to
acute toxic effects of endrin. In an endrin poisoning episode in Pakistan (of unknown origin), children 1–
9 years old represented about 70% of the cases of convulsions (Rowley et al. 1987). The causative factor
responsible for the outbreak was not identified, however, so it is unclear whether the age distribution of
cases was due to increased susceptibility in children or age-specific exposure situations. Available data

ENDRIN 117
from oral developmental studies in animals do not indicate that developing animals are uniquely
susceptible to toxicity following exposure to endrin.
Physical and Chemical Properties. More complete information on the physical and chemical
properties of endrin aldehyde and endrin ketone would be useful. However, the physical and chemical
properties of endrin have been sufficiently documented to permit estimation of its environmental fate.
Production, Import/Export, Use, Release, and Disposal. Information as to whether endrin is

currently being produced and the export volumes for endrin are needed to evaluate existing routes of
exposure for the general population and occupationally exposed individuals. Endrin is no longer
registered for use and is not likely to be imported into the United States. Consequently, the risk of human
exposure to endrin (and to endrin aldehyde and endrin ketone, which occur as impurities or
transformation products of endrin) from these activities is expected to be minimal. However, recent
information suggests that several organochlorine pesticides that have been banned from use or have been
voluntarily cancelled in the United States are still being manufactured in large quantities for export
abroad.
Environmental Fate. Anaerobic biodegradation, which may occur in river bottoms and in Superfund
sites, has been studied in the laboratory, but not under natural conditions. Further information on these
processes, including identification of degradation products, would be useful in determining potential
mechanisms and the potential for contamination of groundwater by endrin released from soils. The
partitioning of endrin released to the environment and the potential for bioaccumulation is well
characterized. Information on biodegradation of endrin in soil under aerobic conditions exists, but
degradation products have not been identified.
Bioavailability from Environmental Media. Additional information regarding the bioavailability of

endrin from both ingestion of soil-bound endrin and dermal contact with endrin-contaminated soils would
be helpful, particularly for populations living near hazardous waste sites. Information on absorption
following inhalation and oral exposure, however, is well characterized under most conditions.
Food Chain Bioaccumulation. Data on bioaccumulation and bioconcentration of endrin generally

appear to be adequate, particularly since endrin has not been used in the United States since the mid-
1980s. Although bioconcentration data are available for several species, it may be useful to obtain

ENDRIN 118
information on bioconcentration in the species with the highest BCF factor (snail) since data are only
available in the pouch snail.
Exposure Levels in Environmental Media. There are possibilities of exposure from foodstuffs
imported from countries that still use endrin and potential localized risks from exposures near waste
disposal sites or from groundwater contaminated with endrin. Additional data on environmental
concentrations of endrin, endrin aldehyde, and endrin ketone from these possible sources of exposure
would be useful. In addition, reliable monitoring data for the levels of endrin, endrin aldehyde, and
endrin ketone in contaminated media at hazardous waste sites are needed so that the information obtained
on levels of these substances in the environment can be used in combination with their known body
burdens to assess the potential risk of adverse health effects in populations living in the vicinity of
hazardous waste sites. Endrin has been reported to occur at very low levels in food and air. It has only
rarely been detected in a number of national and regional surveys of drinking water supplies. Because
endrin is no longer commercially used in the United States, future levels of endrin, endrin aldehyde, and
endrin ketone in environmental media are expected to be low.
Exposure Levels in Humans. No studies specifically evaluating levels of endrin, endrin aldehyde, or
endrin ketone in blood and other tissues of people near hazardous waste sites were located. This
information is necessary for assessing the need to conduct health studies on these populations. Data on
the concentrations of endrin in breast milk from U.S. women would be particularly useful, given that it
has been detected in the milk of lactating women in other countries. However, metabolism of endrin in
humans is relatively rapid compared with other organochlorine pesticides. Thus, levels in human blood
and tissue may only be useful for acute exposures or very high occupational exposures. Endrin was not
found in adipose tissue samples of the general U.S. population, or in adipose breast tissue from breast
cancer patients in the United States.
Exposures of Children. Children may be exposed to endrin through the same routes as adults, as well
as via placental transfer and breastfeeding. Monitoring of children’s exposure to endrin would be useful,
particularly in heavily contaminated areas, in combination with children’s health and susceptibility
information, to assess the potential risk for deleterious effects.
6.3 Ongoing Studies
No ongoing studies were identified for endrin.

ENDRIN 119
CHAPTER 7. REGULATIONS AND GUIDELINES
Pertinent international and national regulations, advisories, and guidelines regarding endrin in air, water,
and other media are summarized in Table 7-1. This table is not an exhaustive list, and current regulations
should be verified by the appropriate regulatory agency.
ATSDR develops MRLs, which are substance-specific guidelines intended to serve as screening levels by
ATSDR health assessors and other responders to identify contaminants and potential health effects that
may be of concern at hazardous waste sites. See Section 1.3 and Appendix A for detailed information on
the MRLs for endrin.
Table 7-1. Regulations and Guidelines Applicable to Endrin
Agency Description Information Reference

Air
EPA RfC No data IRIS 2002
WHO Air quality guidelines No data WHO 2010
Water & Food
EPA Drinking water standards and health advisories EPA 2012
1-Day health advisory (10-kg child) 0.02 mg/L
10-Day health advisory (10-kg child) 0.005 mg/L
DWEL 0.01 mg/L
Lifetime health advisory 0.002 mg/L
-4
10 Cancer risk No data
National primary drinking water regulations EPA 2009
MCL 0.002 mg/L
PHG 0.002 mg/L
RfD 3x10-4 mg/kg/day IRIS 2002
WHO Drinking water quality guidelines WHO 2017
Guideline value 0.0006 mg/L (0.6 µg/L)
PTDI 0.2 µg/kg body weight
FDA EAFUS No dataa FDA 2013
Allowable level in bottled water 0.002 mg/L FDA 2017
Cancer
HHS Carcinogenicity classification No data NTP 2016
EPA Carcinogenicity classification Db IRIS 2002
IARC Carcinogenicity classification Group 3c IARC 1987

ENDRIN 120
7. REGULATIONS AND GUIDELINES
Table 7-1. Regulations and Guidelines Applicable to Endrin
Agency Description Information Reference

Occupational
OSHA PEL (8-hour TWA) for general industry, 0.1 mg/m3 d OSHA 2016a,
shipyards and construction 2016b, 2017
NIOSH REL (up to 10-hour TWA) 0.1 mg/m3 d NIOSH 2016
IDLH 2 mg/m3 NIOSH 1994
Emergency Criteria
EPA AEGLs-air No data EPA 2016
DOE PACs-air DOE 2018b
PAC-1e 1.8 mg/m3
PAC-2e 20 mg/m3
PAC-3e 2,000 mg/m3
aThe EAFUS list of substances contains ingredients added directly to food that FDA has either approved as food
additives or listed or affirmed as GRAS.
bGroup D: not classifiable as to human carcinogenicity.
cGroup 3: not classifiable as to its carcinogenicity to humans.
dSkin designation.
eDefinitions of PAC terminology are available from U.S. Department of Energy (DOE 2018a).
AEGL = acute exposure guideline levels; DOE = Department of Energy; DWEL = drinking water equivalent level;
EAFUS = Everything Added to Food in the United States; EPA = Environmental Protection Agency; FDA = Food and
Drug Administration; GRAS = generally recognized as safe; HHS = Department of Health and Human Services;
IARC = International Agency for Research on Cancer; IDLH = Immediately Dangerous to Life or Health;
IRIS = Integrated Risk Information System; MCL = maximum contaminant level; NIOSH = National Institute for
Occupational Safety and Health; NTP = National Toxicology Program; OSHA = Occupational Safety and Health
Administration; PAC = Protective Action Criteria; PEL = permissible exposure limit; PHG = public health goal;
PTDI = provisional tolerable daily intake; REL = recommended exposure limit; RfC = inhalation reference
concentration; RfD = oral reference dose; TWA = time-weighted average; WHO = World Health Organization

ENDRIN 121
CHAPTER 8. REFERENCES
*ACGIH. 1986. Documentation of the threshold limit values and biological exposure indices. 5th ed.
Cincinnati, OH: American Conference of Governmental Industrial Hygienists.
*ACGIH. 1988. Threshold limit values for chemical substances and physical agents and biological
exposure indices (1988-1989). Cincinnati, OH: American Conference of Governmental Industrial
Hygienists.
ACGIH. 1991. Threshold limit values for chemical substances and physical agents and biological
exposure indices (1991-1992). Cincinnati, OH: American Conference of Governmental Industrial
Hygienists.
*ACGIH. 2001. Endrin. Documentation of the threshold limit values and biological exposure indices.
Vol. 2. American Conference of Governmental Industrial Hygienists.
*Ahmed FE, Hattis D, Wolke RE, et al. 1993. Risk assessment and management of chemical
contaminants in fishery products consumed in the USA. J Appl Toxicol 13(6):395-410.
+*Akubue PI, Stohs SJ. 1992. Endrin-induced production of nitric oxide by rat peritoneal macrophages.
Toxicol Lett 62:311-316.
*Alawi MA, Ammari N, Al-Shuraiki. 1992. Organochlorine pesticide contaminations in human milk
samples from women living in Amman, Jordan. Arch Environ Contam Toxicol 23:235-239.
*Alawi MA, Tamimi S, Jaghabir M. 1999. Storage of organochlorine pesticides in human adipose
tissues of Jordanian males and females. Chemosphere 38(12):2865-2873.
+*Ali SS, Shakoori R. 1993. Short-term toxicity of endrin in Sprague Dawley rats: Biochemical and
histological changes in liver. Punjab Univ J Zool 8:1-13.
*Allen EM, Florang VR, Davenport LL, et al. 2013. Cellular localization of dieldrin and structure-
activity relationship of dieldrin analogues in dopaminergic cells. Chem Res Toxicol 26(7):1043-
1054. 10.1021/tx300458b.
*Ambrus A, Lantos J, Visi E, et al. 1981. General method for determination of pesticide residues in
samples of plant origin, soil and water: I. Extraction and cleanup. J Assoc Off Anal Chem 64:733-
742.
*Ames BN, McCann J, Yamasaki E. 1975. Methods for detecting carcinogens and mutagens with the
salmonella/mammalian - microsome mutagenicity test. Mutat Res 3:347-364.
*Andersen RL, DeFoe DL. 1980. Toxicity and bioaccumulation of endrin and methoxychlor in aquatic
invertebrates and fish. Environ Pollut 22(2):111-121.
*Argyle RL, Williams GC, Dupree HK. 1973. Endrin uptake and release by fingering channel (Ictalurus
punctatus). J Fish Res Board Can 30:1743-1744.
*ASTER. 1995. ASTER (Assessment Tools for the Evaluation of Risk) ecotoxicity profile. U.S.
Environmental Protection Agency, Office of Research and Development, National Health and
Environmental Effects Research Laboratory. Mid-Continent Ecology Division.
*ASTM. 1988. Method D 3086-85. Standard test method for organochlorine pesticides in water. 1988
annual book of ASTM standards. Vol. 11.02: Water and environmental technology. Philadelphia,
PA: American Society for Testing and Materials, 163-178.
*ATSDR. 1989. Decision guide for identifying substance-specific data needs related to toxicological
profiles; Notice. Fed Regist 54(174):37618-37634.
*ATSDR. 2017. Endrin, endrin aldehyde and endrin ketone. Full SPL data. Substance priority list
(SPL) resource page. Agency for Toxic Substances and Disease Registry, Centers for Disease
Control and Prevention. http://www.atsdr.cdc.gov/SPL/resources/index.html. October 6, 2017.
_______________________
* Cited in text
+ Cited in supplemental document

ENDRIN 122
8. REFERENCES
*ATSDR/CDC. 1990. Subcommittee report on biological indicators of organ damage. Atlanta, GA:
Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention.
+*Bagchi D, Bagchi M, Hassoun E, et al. 1992b. Endrin-induced urinary excretion of formaldehyde,
acetaldehyde, malondialdehyde and acetone in rats. Toxicology 75:81-89.
+*Bagchi D, Bagchi M, Hassoun E, et al. 1992c. Effect of endrin on the hepatic distribution of iron and
calcium in female Sprague-Dawley rats. J Biochem Toxicol 7(1):37-42.
*Bagchi D, Bagchi M, Hassoun EA, et al. 1995a. In vitro and in vivo generation of reactive oxygen
species, DNA damage and lactate dehydrogenase leakage by selected pesticides. Toxicology 104(1-
3):129-140.
*Bagchi D, Bagchi M, Tang L, et al. 1997. Comparative in vitro and in vivo protein kinase C activation
by selected pesticides and transition metal salts. Toxicol Lett 91(1):31-37.
*Bagchi D, Balmoori J, Bagchi M, et al. 2000. Role of p53 tumor suppressor gene in the toxicity of
TCDD, endrin, naphthalene, and chromium (VI) in liver and brain tissues of mice. Free Radic Biol
Med 28(6):895-903.
*Bagchi D, Balmoori J, Bagchi M, et al. 2002. Comparative effects of TCDD, endrin, naphthalene and
chromium (VI) on oxidative stress and tissue damage in the liver and brain tissues of mice.
Toxicology 175(1-3):73-82.
*Bagchi D, Bhattacharya G, Stohs SJ. 1996. In vitro and in vivo induction of heat shock (stress) protein
(Hsp) gene expression by selected pesticides. Toxicology 112(1):57-68.
+*Bagchi D, Hassoun EA, Bagchi M, et al. 1993c. Protective effects of antioxidants against endrin-
induced hepatic lipid peroxidation, DNA damage, and excretion of urinary lipid metabolites. Free
Radic Biol Med 15:217-222.
+*Bagchi E, Hassoun E, Akubue P, et al. 1993d. Comparative effects of endrin on hepatic lipid
peroxidation and DNA damage, and nitric oxide production by peritoneal macrophages from
C57BW6J and DBA/2 mice. Comp Biochem Physiol 105C(3):525-529.
*Bagchi M, Ghosh S, Bagchi D, et al. 1995b. Protective effects of lazaroid U74389F (16-desmethyl
tirilazad) on endrin-induced lipid peroxidation and DNA damage in brain and liver and regional
distribution of catalase activity in rat brain. Free Radic Biol Med 19(6):867-872.
+*Bagchi M, Hassoun EA, Bagchi D, et al. 1993a. Production of reactive oxygen species by peritoneal
macrophages and hepatic mitochondria and microsomes from endrin-treated rats. Free Radic Biol
Med 14:149-155.
+*Bagchi M, Hassoun EA, Stohs SJ. 1992a. Endrin-induced increases in hepatic lipid peroxidation,
membrane microviscosity, and DNA damage in rats. Arch Environ Contam Toxicol 23:1-5.
*Baldwin MK, Hutson DH. 1980. Analysis of human urine for a metabolite of endrin by chemical
oxidation and gas-liquid chromatography as an indicator of exposure to endrin. Analyst 105:60-65.
*Baldwin MK, Crayford JV, Hutson DH, et al. 1976. The metabolism and residues of [14C] endrin in
lactating cows and laying hens. Pestic Sci 7:575-594.
*Baldwin MK, Robinson J, Parke DV. 1970. Metabolism of endrin in the rat. J Agric Food Chem
18:1117-1123.
*Bandyopadhyay SK, Tiwari RK, Mitra P, et al. 1982. Effects of L-ascorbic acid supplementation on
dieldrin toxicity in rats. Arch Toxicol 50:227-232.
+*Bapayeva G, Issayeva R, Zhumadilova A, et al. 2016. Organochlorine pesticides and female puberty
in South Kazakhstan. Reprod Toxicol 65:67-75. 10.1016/j.reprotox.2016.06.017.
*Barcarolo R, Tealdo E, Tutta C. 1988. Multiresidue determination of organochlorine and triazine
pesticides in homogenized milk. J High Resolut Chromatogr Comm 11:10746-10748.
*Barnes DG, Dourson M. 1988. Reference dose (RfD): Description and use in health risk assessments.
Regul Toxicol Pharmacol 8:471-486.
*Bartha R, Lanzilotta RP, Pramer D. 1967. Stability and effects of some pesticides in soil. Appl
Microbiol 15:67-75.

ENDRIN 123
8. REFERENCES
*Bason CW, Colborn T. 1992. U.S. application and distribution of pesticides and industrial chemicals
capable of disrupting endocrine and immune systems. In: Mehlman MA, ed. Chemically-induced
alterations in sexual and functional development: The Wildlife/Human Connection, Vol XXI.
Princeton Scientific Publishing Co., 335-345.
*Beall M Jr, Harris WG, Nash RG. 1972. Endrin transformations in soil. J Environ Qual 1(4):391-394.
*Bedford CT, Harrod RK, Hoadley EC, et al. 1975b. The metabolic fate of endrin in the rabbit.
Xenobiotica 5:485-500.
+*Bedford CT, Hutson DH, Natoff IL. 1975a. The acute toxicity of endrin and its metabolites to rats.
Toxicol Appl Pharmacol 33:115-121.
*Bedi JS, Gill JP, Aulakh RS, et al. 2013. Pesticide residues in human breast milk: Risk assessment for
infants from Punjab, India. Sci Total Environ 463-464:720-726. 10.1016/j.scitotenv.2013.06.066.
*Bentabol A, Jodral M. 1995. Determination of organochlorine pesticides in cheese. J AOAC Int
78(1):94-98.
*Beyer WN, Stafford C. 1993. Survey and evaluation of contaminants in earthworms and in soils
derived from dredged materials at confined disposal facilities in the Great Lakes region. Environ
Monit Assess 24:151-165.
*Bidleman TF. 1981. Interlaboratory analysis of high molecular weight organochlorines in ambient air.
Atmos Environ 15:619-624.
*Bishop FS. 1984. Written communication (August 29) to Velsicol Chemical Company, regarding
notice of intent to cancel registration: Velsicol technical endrin. EPA registration No. 876-20.
Washington, DC: U.S. Environmental Protection Agency, Office of Pesticide Programs,
Registration Division.
*Bishop FS. 1985. Written communication (July 29) to Velsicol Chemical Company, regarding final
cancellation notice: Velsicol technical endrin. EPA registration No. 876.20. Washington, DC: U.S.
Environmental Protection Agency, Office of Pesticide Programs, Registration Division.
*Bishop FS. 1986. Written communication (July 2) to Velsicol Chemical Corporation, Chicago, IL,
regarding notice of intent to cancel the registration of certain pesticide products: Velsicol endrin 1.6
EC. EPA registration No. 876-153. Washington, DC: U.S. Environmental Protection Agency,
Office of Pesticides and Toxic Substances.
*Bloomquist JR. 1992. Intrinsic lethality of chloride-channel-directed insecticides and convulsants in
mammals. Toxicol Lett 60:289-298.
*Blus LJ, Henny CJ, Grove RA. 1989. Rise and fall of endrin usage in Washington State fruit orchards:
Effects on wildlife. Environ Pollut 60:331-349.
+*Boada LD, Henriquez-Hernandez LA, Zumbado M, et al. 2016. Organochlorine pesticides exposure
and bladder cancer: Evaluation from a gene-environment perspective in a hospital-based case-
control study in the Canary Islands (Spain). J Agromedicine 21(1):34-42.
10.1080/1059924x.2015.1106374.
+*Boada LD, Zumbado M, Henriquez-Hernandez LA, et al. 2012. Complex organochlorine pesticide
mixtures as determinant factor for breast cancer risk: A population-based case-control study in the
Canary Islands (Spain). Environ Health 11:28. 10.1186/1476-069x-11-28.
*Bordet F, Mallet J, Maurice L, et al. 1993. Organochlorine pesticide and PCB congener content of
French human milk. Bull Environ Contam Toxicol 50:425-432.
*Burse VW, Head SL, Korver MP, et al. 1990. Determination of selected organochlorine pesticides and
polychlorinated biphenyls in human serum. J Anal Toxicol 14:137-142.
*Burton WB, Pollard GE. 1974. Rate of photochemical isomerization of endrin in sunlight. Bull
Environ Contam Toxicol 12:113-116.
*Buttner JK, Makarewicz JC, Lewis TW. 1995. Concentration of selected priority organic contaminants
in fish maintained on formulated diets in Lake Ontario waters. Prog Fish-Cult 57:141-146.
+*Carbajal-Rodriguez L, Oldak-Skvirsky D, Loreda-Abdala A, et al. 1990. Intoxicatiόn por endrin. Bol
Med Hosp Infant Mex 47(2):100-102.

ENDRIN 124
8. REFERENCES
*Carey AE, Kutz FW. 1985. Trends in ambient concentrations of agrochemicals in humans and the
environment of the United States. Environ Monit Assess 5:155-163.
*Carey AE, Gowen JA, Tai H, et al. 1979. Pesticide residue levels in soils and crops from 37 states,
1972 National Soils Monitoring Program (IV). Pestic Monit J 12:209-229.
*Carey AE, Wiersma GB, Tai H. 1976. Pesticide residues in urban soils from 14 United States cities,
1970. Pestic Monit J 10(2):54-60.
*Carey AE, Yang HSC, Wiersma GB, et al. 1980. Residual concentrations of propanil, TCAB and other
pesticides in rice-growing soils in the United States, 1972. Pestic Monit J 14:23-25.
Carrero I, Fernandez-Moreno MD, Perez-Albarsanz MA, et al. 1989. Lindane effect upon the vasoactive
intestinal peptide receptor-effector system in rat enterocytes. Biochem Biophys Res Comm
159(3):1391-1396.
Carrero I, Perez-Albarsanz MA, Carmena MJ, et al. 1990. Lindane inhibits β-adrenergic stimulation of
cyclic AMP accumulation in rat prostatic epithelial cells. Pestic Biochem Physiol 38:197-203.
*CDC. 2018. Fourth national report on human exposure to environmental chemicals. Updated tables,
March 2018. Centers for Disease Control and Prevention, U.S. Department of Health and Human
Services.
https://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Volume2_Mar2018.pdf.
April 06, 2018.
CELDS. 1993. Computer-assisted Environmental Legislative Database. University of Illinois at Urbana.
*Chan CH, Bruce G, Harrison B. 1994. Wet deposition of organochlorine pesticides and polychlorinated
biphenyls to the Great Lakes. J Great Lakes Res 20(3):546-560.
Chernoff N, Kavlock RJ, Gray LE, et al. 1979b. Teratogenic effects of endrin in the golden hamster
[Abstract]. Toxicol Appl Pharmacol 48:A201.
+*Chernoff N, Kavlock RJ, Hanisch RC, et al. 1979a. Perinatal toxicity of endrin in rodents. 1.
Fetotoxic effects of prenatal exposure in hamsters. Toxicology 13:155-165.
*Clayton GD, Clayton FE. 1981. Patty’s industrial hygiene and toxicology. Volume 2B: Toxicology.
3rd ed. New York, NY: John Wiley & Sons, 3685.
*Clewell HJ, Andersen ME. 1985. Risk assessment extrapolations and physiological modeling. Toxicol
Ind Health 1(4):111-131.
+*Coble Y, Hildebrandt P, Davis J, et al. 1967. Acute endrin poisoning. JAMA 202:489-493.
+*Cocco P, Brennan P, Ibba A, et al. 2008. Plasma polychlorobiphenyl and organochlorine pesticide
level and risk of major lymphoma subtypes. Occup Environ Med 65(2):132-140.
10.1136/oem.2007.033548.
*Cohen DB. 1986. Ground water contamination by toxic substances, California assessment.
Sacramento, CA: State Water Resources Control Board, Pollutant Investigations Branch. American
Chemical Society.
Cole JF, Klevay LM, Zavon MR. 1970. Endrin and dieldrin: A comparison of hepatic excretion in the
rat. Toxicol Applied Pharmacol 16:547-555.
*Cole RH, Frederick RE, Healy RP, et al. 1984. Preliminary findings of the priority pollutant monitoring
project of the Nationwide Urban Runoff Program. J Water Pollut Control Fed 56(7):898-908.
Coleman RL. 1968. Endrin induced alterations in bound carbohydrates in rat serum. Bull Environ
Contam Toxicol 3(6):348-353. 10.1007/bf01558351.
+*Coleman RL, Lawrence CH, Sowell WL. 1968. Trace metal alterations following sub-acute exposure
to endrin. Bull Environ Contam Toxicol 3(5):284-295. http://doi.org/10.1007/bf01623626.
+Cook WO, Casteel SW. 1985. A suspected case of endrin toxicosis in a cat. Vet Hum Toxicol
27(2):111.
*Crespo C, Marce RM, Borrull F. 1994. Determination of various pesticides using membrane extraction
discs and gas chromatography mass spectrometry. J Chromatogr 670(1-2):135-144.
*Cruz I, Wells DE, Mat-r IL. 1993. Determination of organochlorines in sea water: An assessment.
Anal Chim Acta 283:280-286.

ENDRIN 125
8. REFERENCES
+*Curley A, Jennings RW, Mann HT, et al. 1970. Measurement of endrin following epidemics of
poisoning. Bull Environ Contam Toxicol 5:24-29.
+*Davies GM, Lewis I. 1956. Outbreak of food poisoning from bread made of chemically contaminated
flour. Br Med J 11:393-398.
*Davies K. 1988. Concentrations and dietary intake of selected organochlorines, including PCBs,
PCDDs and PCDFs in fresh food composites grown in Ontario, Canada. Chemosphere 17(2):263-
276.
*De Bruijin J, Busser F, Seinem W, et al. 1989. Determination of octanol water partition coefficients for
hydrophobic organic chemicals with the “slow-stirring” method. Environ Toxicol Chem 8:499-512.
*De Peyster A, Donohoe R, Slymen DJ. 1993. Aquatic biomonitoring of reclaimed water for potable
use: The San Diego health effects study. J Toxicol Environ Health 39:121-142.
+*Deichmann WB, MacDonald WE, Blum E, et al. 1970. Tumorigenicity of aldrin, dieldrin and endrin
in the albino rat. Ind Med 39:37-45.
*Dewailly E, Ayotte P, Bruneau S, et al. 1993. Inuit exposure to organochlorines through the aquatic
food chain in arctic Quebec. Environ Health Perspect 101:618-620.
*Dikshith TSS, Datta KK. 1973. Endrin induced cytological changes in albino rats. Bull Environ
Contam Toxicol 9(2):65-69.
*Di Muccio A, Ausili A, Dommarco R, et al. 1991. Solid-matrix partition for separation of
organochlorine pesticide residues from fatty materials. J Chromatogr 552:241-247.
*Di Muccio A, Santilio A, Dommarco R, et al. 1990. Behaviour of 23 persistent organochlorine
compounds during sulphuric acid clean-up on a solid-matrix column. J Chromatogr 513:333-337.
+*Ditraglia D, Brown DP, Namekata T, et al. 1981. Mortality study of workers employed at
organochlorine pesticide manufacturing plants. Scand J Work Environ Health 7:140-146.
*Djordjevic MV, Hofmann D, Fan J. 1994. Assessment of chlorinated pesticides and polychlorinated
biphenyls in adipose breast tissue using a supercritical fluid extraction method. Carcinogenesis
15(11):2581-2585.
*DOE. 2018a. Protective Action Criteria (PAC) with AEGLs, ERPGs, & TEELs: ev. 29A, June 2018.
Oak Ridge, TN: U.S. Department of Energy. https://sp.eota.energy.gov/pac/. July 26, 2018.
*DOE. 2018b. Table 3: Protective Action Criteria (PAC) Rev. 29a based on applicable 60-minute
AEGLs, ERPGs, or TEELs. The chemicals are listed by CASRN. June 2018. Oak Ridge, TN: U.S.
Department of Energy. https://sp.eota.energy.gov/pac/docs/Revision_29A_Table3.pdf. July 26,
2018.
*Doherty FG, Evans DW, Neuhauser EF. 1993. An assessment of total and leachable contaminants in
zebra mussels (Dreissena polymorpha) from Lake Erie. Ectotoxicol Environ Saf 25:328-340.
*Eichelberger JW, Lichtenberg JJ. 1971. Persistence of pesticides in river water. Environ Sci Technol
5(6):541-544.
+*Eisenlord G, Loquvam GS, Leung S. 1968. Results of reproduction study of rats fed diets containing
endrin over three generations. Prepared by Hine Laboratories for Shell Chemical Co., and Velsicol
Chemical Corp.
*Eisenreich SJ, Looney BB, Thornton JD. 1981. Airborne organic contaminants in the Great Lakes
ecosystem. Environ Sci Technol 15:30-38.
*Ellenhorn MJ, Barceloux DG. 1988. Medical toxicology diagnosis and treatment of human poisoning.
New York, NY: Elsevier, 1078-1080.
+*El Morsi DA. 2012. Pesticides residues in Egyptian diabetic children: A preliminary study. J Clin
Toxicol 2:138. 10.4172/2161-0495.1000138.
*EPA. 1971. Tolerances and exemptions from tolerances for pesticide chemicals in or on raw
agricultural commodities. U.S. Environmental Protection Agency. Code of Federal Regulations. 40
CFR 180.
*EPA. 1973. Guidelines establishing test procedures for the analysis of pollutants. U.S. Environmental
Protection Agency. Code of Federal Regulations. 40 CFR 136.

ENDRIN 126
8. REFERENCES
*EPA. 1975. National primary drinking water regulations. U.S. Environmental Protection Agency.
Code of Federal Regulations. 40 CFR 141.
EPA. 1976a. Endrin: Position Document I. Arlington, VA: U.S. Environmental Protection Agency,
Special Pesticide Review Division. EPASPRD8037. PB81-112690.
*EPA. 1976b. National primary drinking water regulations implementation. U.S. Environmental
Protection Agency. Code of Federal Regulations. 40 CFR 142.62.
*EPA. 1977a. Regulatory limitation. U.S. Environmental Protection Agency. Code of Federal
Regulations. 40 CFR 129.102.
*EPA. 1977b. Tolerances for residues. U.S. Environmental Protection Agency. Code of Federal
*EPA. 1977c. Toxic pollutant effluent standards. U.S. Environmental Protection Agency. Code of
Federal Regulations. 40 CFR 129.
*EPA. 1978a. Designation of hazardous substances. U.S. Environmental Protection Agency. Code of
Federal Regulations. 40 CFR 116.4.
*EPA. 1978b. Pesticide chemicals. U.S. Environmental Protection Agency. Code of Federal
*EPA. 1979a. Determination of reportable quantities for hazardous substances. U.S. Environmental
*EPA. 1979b. Criteria and standards for the national pollutant discharge elimination system. U.S.
Environmental Protection Agency. Code of Federal Regulations. 40 CFR 125.
*EPA. 1979c. Toxic pollutants. U.S. Environmental Protection Agency. Code of Federal Regulations.
40 CFR 401.15.
*EPA. 1979d. Criteria for classification of solid waste disposal facilities and practices. U.S.
Environmental Protection Agency. Code of Federal Regulations. 40 CFR 257.
*EPA. 1979e. U.S. Environmental Protection Agency: Part II. Fed Regist 44:43632-43657.
*EPA. 1979f. Endrin: Position document 4. Washington, DC: U.S. Environmental Protection Agency,
Special Pesticide Review Division. EPASPRD8039. PB81109480.
*EPA. 1979g. Water-related environmental fate of 129 priority pollutants. Vol I: Introduction and
technical background, metals and inorganics, pesticides and PCBs. Washington, DC: U.S.
Environmental Protection Agency, Office of Water Planning and Standards. EPA440479029a.
*EPA. 1980a. Ambient water quality criteria document for endrin. U.S. Environmental Protection
Agency. Prepared by the Office of Health and Environmental Assessment, Environmental Criteria
and Assessment Office, Cincinnati, OH, for the Office of Water Regulations and Standards,
Washington, DC.
*EPA. 1980b. Identification and listing of hazardous waste. U.S. Environmental Protection Agency.
Code of Federal Regulations. 40 CFR 261.
*EPA. 1980c. Standards for owners and operators of hazardous waste treatment, storage, and disposal
facilities. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 264.
*EPA. 1980d. Interim status standards for owners and operators of hazardous waste treatment, storage,
and disposal facilities. U.S. Environmental Protection Agency. Code of Federal Regulations. 40
CFR 265.
EPA. 1980e. Chemical contaminants in nonoccupationally exposed U.S. residents. Research Triangle
Park, NC: U.S. Environmental Protection Agency, Office of Research and Development.
EPA600180001.
*EPA. 1981a. Aquatic fate process data for organic priority pollutants. Washington, DC: U.S.
Environmental Protection Agency, Office of Water Regulations and Standards. EPA440481014.
*EPA. 1981b. Electroplating point source category. U.S. Environmental Protection Agency. Code of

ENDRIN 127
8. REFERENCES
*EPA. 1982a. Test method: Organochlorine pesticides and PCBs - Method 608. In: Longbottom JE,
Lichtenberg JJ, eds. Test methods: Methods for organic chemical analysis of municipal and
industrial wastewater. Cincinnati, OH: U.S. Environmental Protection Agency, Environmental
Monitoring and Support Laboratory. EPA600482057.
*EPA. 1982b. Test method: Base/neutrals and acids - Method 625. In: Longbottom JE, Lichtenberg JJ,
eds. Test methods: Methods for organic chemical analysis of municipal and industrial wastewater.
Cincinnati, OH: U.S. Environmental Protection Agency, Environmental Monitoring and Support
Laboratory. EPA600482057.
*EPA. 1982c. Steam electric power generating point source category. U.S. Environmental Protection
Agency. Code of Federal Regulations. 40 CFR 423.
*EPA. 1983a. EPA administered permit programs: The National Pollutant Discharge Elimination
System. U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 122.
*EPA. 1983b. Total toxic organics: Metal finishing point source category. U.S. Environmental
*EPA. 1983c. Aluminum forming. Total toxic organics. U.S. Environmental Protection Agency. Code
of Federal Regulations. 40 CFR 467.02.
EPA. 1983d. Treatability manual: Vol I. Treatability data. Washington DC: U.S. Environmental
Protection Agency, Office of Research and Development. EPA600282001a.
*EPA. 1983e. Status of pesticides in reregistration and special review. Washington, DC: U.S.
Environmental Protection Agency, Office of Prevention, Pesticides and Toxic Substances.
EPA738R93009.
*EPA. 1984a. Analytical reference standards and supplemental data: The pesticides and industrial
chemicals repository. U.S. Environmental Protection Agency, Environmental Monitoring Systems
Laboratory - Las Vegas. EPA600484082.
*EPA. 1984b. Identification of specific chemical substance and mixture testing requirements. U.S.
Environmental Protection Agency. Code of Federal Regulations. 40 CFR 799.5055.
*EPA. 1984c. Method T0-4 for the determination of organochlorine pesticides and polychlorinated
biphenyls. In: Compendium of methods for the determination of toxic organic compounds in
ambient air. Research Triangle Park, NC: U.S. Environmental Protection Agency, Office of
Research and Development. EPA600484041.
*EPA. 1985a. Designation of reportable quantities and notification. U.S. Environmental Protection
*EPA. 1985b. Reporting and recordkeeping requirements. U.S. Environmental Protection Agency.
Code of Federal Regulations. 40 CFR 704.102.
*EPA. 1985c. Environmental effects testing guidelines. U.S. Environmental Protection Agency. Code
of Federal Regulations. 40 CFR 797.1520.
*EPA. 1985d. Standards for the management of specific hazardous wastes and specific types of
hazardous waste management facilities. U.S. Environmental Protection Agency. Code of Federal
Regulations. 40 CFR 266.
*EPA. 1985e. Drinking water criteria document for endrin. Washington, DC: U.S. Environmental
Protection Agency, Office of Drinking Water. EPA600X84176.
EPA. 1985f. Suspended, cancelled and restricted pesticides. 3rd ed. Washington, DC: U.S.
Environmental Protection Agency, Office of Pesticide Programs.
*EPA. 1986a. General pretreatment regulations for existing and new sources of pollution. U.S.
Environmental Protection Agency. Code of Federal Regulations. 40 CFR 403, Appendix B.
*EPA. 1986b. Method 8250: Gas chromatography/mass spectrometry for semivolatile organics: Packed
column technique. In: Test methods for evaluating solid waste. Volume IC: Laboratory manual:
Physical/chemical methods. SW-846. 3rd ed. Washington, DC: U.S. Environmental Protection
Agency, Office of Solid Waste and Emergency Response.

ENDRIN 128
8. REFERENCES
*EPA. 1986c. Method 8270: Gas chromatography/mass spectrometry for semivolatile organics:
Capillary column technique. In: Test methods for evaluating solid waste. Volume IC: Laboratory
manual: Physical/chemical methods. SW-846. 3rd ed. Washington DC: U.S. Environmental
Protection Agency, Office of Solid Waste and Emergency Response.
*EPA. 1986d. Land disposal restrictions. U.S. Environmental Protection Agency. Code of Federal
EPA. 1986e. Reference values for risk assessment. Final draft. Cincinnati, OH: U.S. Environmental
Protection Agency, Office of Solid Waste. ECAO-CIN-477.
*EPA. 1987a. Emergency planning and notification. U.S. Environmental Protection Agency. Code of
*EPA. 1987b. Land disposal restrictions. U.S. Environmental Protection Agency. Code of Federal
*EPA. 1987c. U.S. Environmental Protection Agency: Part V. Fed Regist 52:25760-25763, 25791.
EPA. 1987d. Endrin health advisory. Washington, DC: U.S. Environmental Protection Agency, Office
of Drinking Water.
EPA. 1987e. Health effects assessment of endrin. Cincinnati, OH: U.S. Environmental Protection
Agency, Office of Research and Development. EPA6008881035.
*EPA. 1988a. Toxic chemical release reporting: Community right-to-know. U.S. Environmental
Protection Agency. Code of Federal Regulations. 40 CFR 372.
EPA. 1988b. Pesticide registration and classification procedures. U.S. Environmental Protection
Agency. Code of Federal Regulations. 40 CFR 152.175.
*EPA. 1988c. Land disposal restrictions. U.S. Environmental Protection Agency. Code of Federal
*EPA. 1988d. State water quality standards summaries. Washington, DC: U.S. Environmental
Protection Agency, Office of Water. EPA440588031.
*EPA. 1988e. Method 508. Determination of chlorinated pesticides in water by gas chromatography
with an electron capture detector. In: Methods for the determination of organic compounds in
drinking water (Rev 3.0). Washington, DC: U.S. Environmental Protection Agency, Office of Solid
Waste and Emergency Response. SW 846.
*EPA. 1989. Pesticides in ground water data base: 1988 interim report. Washington, DC: U.S.
Environmental Protection Agency, Office of Pesticide Programs. EPA5400989036.
*EPA. 1990. Interim methods for development of inhalation reference doses. U.S. Environmental
Protection Agency. EPA600890066A.
*EPA. 1991a. National primary drinking water regulations: Maximum contaminant levels and goals.
U.S. Environmental Protection Agency. Code of Federal Regulations. 40 CFR 141.50 and 141.61.
*EPA. 1991b. Criteria for municipal solid waste landfills (Eff. 10-9-93). U.S. Environmental Protection
EPA. 1992a. National primary drinking water regulations: Synthetic organic chemicals and inorganic
chemicals. Final rule. U.S. Environmental Protection Agency. Code of Federal Regulations. 40
CFR 141 and 142.
*EPA. 1992b. National study of chemical residues in fish. Volume I. Washington, DC: U.S.
Environmental Protection Agency, Office of Science and Technology. EPA823R92008A.
EPA. 1992c. Drinking water criteria document for endrin. ECAO-CIN-423.
*EPA. 1993. Proposed water quality guidance for the Great Lakes system. U.S. Environmental
Protection Agency. Code of Federal Regulations. 40 CFR 122,123,131,132.
*EPA. 1994a. Standards for pesticide containers and containment. Proposed rule. U.S. Environmental
Protection Agency. Fed Regist 59:6712-6789.
*EPA. 1994b. Drinking water regulations and health advisories. Washington, DC: U.S. Environmental
Protection Agency, Office of Water.

ENDRIN 129
8. REFERENCES
*EPA. 1995a. Toxic chemical release inventory reporting form R and instructions. Revised 1994
version. Washington DC: U.S. Environmental Protection Agency, Office of Pollution Prevention
and Toxics. EPA745K95051.
*EPA. 1995b. The national listing of fish consumption advisories and bans. Washington DC: U.S.
Environmental Protection Agency, Office of Water. EPA823C95001.
*EPA. 1995c. Method 8270C. Semivolatile organic compounds by gas chromatography mass
spectrometry (GC/MS): Capillary column technique. In: Test methods for evaluating solid waste,
revision 3, January 1995. Washington DC. U.S. Environmental Protection Agency, Office of Solid
Waste and Emergency Response. SW 8465.
*EPA. 1995d. Method 8081A: Organochlorine pesticides by capillary column gas chromatography,
Revision 1, January 1995. In: Test methods for evaluating solid waste, Revision 3, January 1995.
U.S. Environmental Protection Agency, Office of Solid Waste and Emergency Response. SW 846.
*EPA. 2005. Toxic chemical release inventory reporting forms and instructions: Revised 2004 version.
Section 313 of the Emergency Planning and Community Right-to-Know Act (Title III of the
Superfund Amendments and Reauthorization Act of 1986). U.S. Environmental Protection Agency,
Office of Environmental Information. EPA260B05001.
*EPA. 2009. National primary drinking water regulations. Washington, DC: U.S. Environmental
Protection Agency, Office of Ground Water and Drinking Water. EPA816F090004.
https://www.epa.gov/sites/production/files/2016-06/documents/npwdr_complete_table.pdf.
September 7, 2017.
*EPA. 2012. Drinking water standards and health advisories. Washington, DC: U.S. Environmental
Protection Agency, Office of Water. EPA822S12001.
https://www.epa.gov/sites/production/files/2015-09/documents/dwstandards2012.pdf. April 25,
2013.
*EPA. 2016. Acute Exposure Guideline Levels (AEGLs) values. U.S. Environmental Protection
Agency. https://www.epa.gov/sites/production/files/2016-
03/documents/compiled_aegl_update_.pdf. September 8, 2017.
*Ert MV, Sullivan, JP. 1992. Organochlorine pesticides in hazardous materials toxicology: Clinical
principles of environmental health. Baltimore, MD: William & Wilkins, 1047-1048.
Farm Chemicals Handbook. 1994. Berg GL, ed. Willoughby, OH: Meister Publishing Co.
*FASE. 1996. Pesticide exports from US ports, 1992-1994. Foundation for Advancements in Science
and Education. Park Mile Plaza, Los Angeles, CA.
*Fazzalari FA. 1978. ASTM/DS-48A: Compilation of odor and taste threshold values. Philadelphia,
PA: American Society for Testing and Materials, 58
*FDA. 1988. Residues in foods-1987. Food and Drug Administration Program. J Assoc Off Anal
Chem 71(6):156A-174A.
*FDA. 1989. Residues in foods -1988 (2nd Annual FDA Pesticide Residue Monitoring Program
Report). J Assoc Off Anal Chem 72(5):133A-152A.
*FDA. 1990. Residues in foods-1989 (3rd Annual FDA Pesticide Residue Monitoring Program Report).
J Assoc Off Anal Chem 73(5):127A-146A.
*FDA. 1991. Residues in foods-1990 (4th Annual FDA Pesticide Residue Monitoring Program Report).
J Assoc Off Anal Chem 74(5):121A-140A.
*FDA. 1992. Residue monitoring-1991 (5th Annual FDA Pesticide Residue Monitoring Program
Report). J AOAC Int 75(5):135A-157A.
*FDA. 1993. Residue monitoring 1992 (6th Annual FDA Pesticide Residue Monitoring Program
*FDA. 1994a. Residue monitoring 1993 (7th Annual FDA Pesticide Residue Monitoring Program
*FDA. 1994b. 302 and 303 Methods for nonfatty foods. In: Pesticides analytical manual, 3rd edition,
Vol. 1: Multiresidue methods. U.S. Department of Health and Human Services, Food and Drug
Administration.

ENDRIN 130
8. REFERENCES
*FDA. 1994c. 304: Method for fatty foods. In: Pesticide analytical manual, 3rd edition, Vol. 1:
Multiresidue methods. U.S. Department of Health and Human Services, Food and Drug
Administration.
*FDA. 1995. Residue monitoring -1994 (8th Annual FDA Pesticide Residue Monitoring Program
*FDA. 2013. Everything added to food in the United States (EAFUS). Washington, DC: U.S. Food and
Drug Administration. http://www.accessdata.fda.gov/scripts/fcn/fcnnavigation.cfm?rpt=eafuslisting.
January 8, 2014.
*FDA. 2017. Subpart B - Requirements for specific standardized beverages. Bottled water. Code of
Federal Regulations. 21 CFR 165.110
FEDRIP. 1995. Summary of federal research. Federal Research in Progress (FEDRIP) data base, 1995.
+*Fernandez MF, Olmos B, Granada A, et al. 2007. Human exposure to endocrine-disrupting chemicals
and prenatal risk factors for cryptorchidism and hypospadias: A nested case-control study. Environ
Health Perspect 115 Suppl 1:8-14. 10.1289/ehp.9351.
*Finkel AJ. 1983. Hamilton and Hardy’s industrial Toxicology, 4th ed. Littleton, MA: John Wright,
295-297.
*Fleming L, Mann JB, Bean J, et al. 1994. Parkinson’s disease and brain levels of organochlorine
pesticides. Ann Neurol 36(1):98-103.
*Ford M. 1993. Insecticides and pesticides. In: Vicellio P. Handbook of medical toxicology. Boston,
MA: Little Brown and Company, 303-313.
*Ford WM, Hill EP. 1991. Organochlorine pesticides in soil sediments and aquatic animals in the Upper
Steele Bayou watershed of Mississippi. Arch Environ Contam Toxicol 20:161-167.
*Foster GD, Gates PM, Foreman WT. 1993. Determination of dissolved-phase pesticides in surface
water from the Yakima River Basin, Washington, using the Goulden large-sample extractor and gas
chromatography/mass spectrometry. Environ Sci Technol 27(9):1911-1917.
+*Freire C, Koifman RJ, Sarcinelli P, et al. 2012. Long term exposure to organochlorine pesticides and
thyroid function in children from Cidade dos Meninos, Rio de Janeiro, Brazil. Environ Res 117:68-
74. 10.1016/j.envres.2012.06.009.
+*Freire C, Koifman RJ, Sarcinelli PN, et al. 2013. Long-term exposure to organochlorine pesticides
and thyroid status in adults in a heavily contaminated area in Brazil. Environ Res 127:7-15.
10.1016/j.envres.2013.09.001.
+*Freire C, Koifman RJ, Sarcinelli PN, et al. 2014. Association between serum levels of organochlorine
pesticides and sex hormones in adults living in a heavily contaminated area in Brazil. Int J Hyg
Environ Health 217(2-3):370-378. 10.1016/j.ijheh.2013.07.012.
+*Freire C, Lopez-Espinosa MJ, Fernandez M, et al. 2011. Prenatal exposure to organochlorine
pesticides and TSH status in newborns from southern Spain. Sci Total Environ 409(18):3281-3287.
10.1016/j.scitotenv.2011.05.037.
FSTRAC. 1990. Summary of State and Federal Drinking Water Standards and Guidelines. Washington,
DC: U.S. Environmental Protection Agency. Chemical Communication Subcommittee, Federal and
State Toxicology and Regulatory Alliance Committee (FSTRAC).
*Fujii Y, Ito Y, Harada KH, et al. 2012. Comparative survey of levels of chlorinated cyclodiene
pesticides in breast milk from some cities of China, Korea and Japan. Chemosphere 89(4):452-457.
10.1016/j.chemosphere.2012.05.098.
+*Gaines TB. 1960. The acute toxicity of pesticides to rats. Toxicol Appl Pharmacol 2:88-99.
+*Gaines TB. 1969. Acute toxicity of pesticides. Toxicol Appl Pharmacol 14:515-534.
*Ganguly SK, Bhattacharyya J. 1973. Detection of small amounts of pesticides in human biological
material by thin-layer chromatography. Forensic Sci 2:333-338.
*Gartrell MJ, Craun JC, Podrebarac DS, et al. 1986. Pesticides, selected elements, and other chemicals
in adult total diet samples, October 1980-March 1982. J Assoc Off Anal Chem 69:146-161.
*Genuis SJ, Lane K, Birkholz D. 2016. Human elimination of organochlorine pesticides: Blood, urine,
and sweat study. BioMed Res Int 2016:1624643. 10.1155/2016/1624643.

ENDRIN 131
8. REFERENCES
*Ghadiri H, Rose CW, Connell DW. 1995. Degradation of organochlorine pesticides in soils under
controlled environment and outdoor conditions. J Environ Manage 43:141-151.
*Gianessi LP. 1986. A national pesticide usage data base, summary of report submitted to the Office of
Standards and Regulations. Washington, DC: U.S. Environmental Protection Agency under
cooperative agreement CR 811858-01-0 by Resources for the Future.
*Giesy JP, Verbrugge DA, Othout RA, et al. 1994. Contaminants in fishes from Great Lakes-influenced
sections and above dams of three Michigan rivers. I: Concentrations of organochlorine insecticides,
polychlorinated biphenyls, dioxin equivalents, and mercury. Arch Environ Contam Toxicol 27:202-
212.
*Gladen BC, Monaghan SC, Lukyanova EM, et al. 1999. Organochlorines in breast milk from two cities
in Ukraine. Environ Health Perspect 107(6):459-462.
*Glatt H, Jung R, Oesch F. 1983. Bacterial mutagenicity investigation of epoxides: Drugs, drug
metabolites, steroids and pesticides. Mutat Res 11:99-118.
+*Goldenthal EI. 1978a. Endrin: Teratology study in rats. Prepared by International Research and
Development Corporation for Velsicol Chemical Corporation.
+*Goldenthal EI. 1978b. Endrin: Teratology study in hamsters. Prepared by International Research and
Development Corporation for Velsicol Chemical Corporation.
+*Good EE, Ware GW. 1969. Effects of insecticides on reproduction in the laboratory mouse: IV.
Endrin and dieldrin. Toxicol Appl Pharmacol 14:201-203.
Gosselin RE, Smith RP, Hodge HC, et al. 1984. Clinical toxicology of commercial products. 5th ed.
Baltimore, MD: Williams and Wilkins, 11-285.
*Gowda TK, Sethunathan N. 1976. Persistence of endrin in Indian rice soils under flooded conditions. J
Agric Food Chem 24:750-753.
+*Gray LE Jr, Kavlock RJ, Chernoff N, et al. 1981. Perinatal toxicity of endrin in rodents. III.
Alterations of behavioral ontogeny. Toxicology 21:187-202.
*Greenberg AE, Clesceri LS, Easton AD, eds. 1992. Method 6630c9: Standard methods for the
examination of water and wastewater, 18th edition. Washington, DC: American Public Health
Association.
*Grab K, Wagner C. 1993. Procedure for testing inertness of inserts and insert packing materials for GC
injectors. J High Resolut Chromatogr 16:464-568.
*Guillette EA, Meza MM, Aquilar MG, et al. 1998. An anthropological approach to the evaluation of
preschool children exposed to pesticides in Mexico. Environ Health Perspect 106(6):347-353.
*Gunderson EL. 1988. Chemical contaminants monitoring: FDA total diet study, April 1982-April
1984, dietary intakes of pesticides, selected elements, and other chemicals. J Assoc Off Anal Chem
71(6):1200-1209.
*Hansen DJ Schimmel SC, Forester J. 1977. Endrin: Effects on the entire life-cycle of saltwater fish,
Cyprinbdon variegatus. J Toxicol Environ Health 3:721-733.
*Harkov R. 1986. Semivolatile organic compounds in the atmosphere: A review. J Environ Sci Health
409-433.
*Harrington-Fowler L. 1991. Application of a one-step extractor/concentrator in environmental testing.
Am Lab (August 1991):39-42.
*Hartgrove RW Jr., Hundley SG, Webb RE. 1977. Characterization of the hepatic mixed function
oxidase system in endrin-resistant and -susceptible pine voles. Pestic Biochem Physiol 7:146-153.
+*Hassan MQ, Numan IT, Al-Nasiri N, et al. 1991. Endrin-induced histopathological changes and lipid
peroxidation in livers and kidneys of rats, mice, guinea pigs and hamsters. Toxicol Pathol
19(2):108-114.
+*Hassoun EA, Stohs SJ. 1996a. TCDD, endrin and lindane induced oxidative stress in fetal and
placental tissues of C57BL/6J and DBA/2J mice. Comp Biochem Physiol C Pharmacol Toxicol
Endocrinol 115(1):11-18.

ENDRIN 132
8. REFERENCES
+*Hassoun EA, Stohs SJ. 1996b. Comparative teratological studies on TCDD, endrin and lindane in
C57BL/6J and DBA/2J mice. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 113(3):393-
398.
+*Hassoun E, Bagchi M, Bagchi D, et al. 1993. Comparative studies on lipid peroxidation and DNA-
single strand breaks induced by lindane, DDT, chlordane and endrin in rats. Comp Biochem Physiol
104C(3):427-431.
+*Hassoun EA, Bagchi D, Stohs SJ. 1996. TCDD, endrin and lindane induced increases in lipid
metabolites in maternal sera and amniotic fluids of pregnant C57BL/6J and DBA/2J mice. Res
Commun Mol Pathol Pharmacol 94(2):157-169.
Hayes JR, Hartgrove RW, Hundley SG, et al. 1975. Interaction of endrin and dieldrin with hepatic
microsomal cytochrome 450 from the rat, mouse, and endrin-susceptible and resistant pine voles.
Toxicol Appl Pharmacol 32:559-565.
+*Hayes WJ Jr. 1963. Clinical handbook on economic poisons: Emergency information for treating
poisoning. Atlanta, GA: U.S. Department of Health, Education, and Welfare, Public Health Service,
Communicable Disease Center -Toxicology Section.
*Hellou J, Warren WG, Payne JF. 1993. Organochlorines including polychlorinated biphenyls in
muscle, liver, and ovaries of cod, Gadus morhua. Arch Environ Contam Toxicol 25:497-505.
+*Henriquez-Hernandez LA, Luzardo OP, Zumbado M, et al. 2014. Blood pressure in relation to
contamination by polychlorobiphenyls and organochlorine pesticides: Results from a population-
based study in the Canary Islands (Spain). Environ Res 135:48-54. 10.1016/j.envres.2014.05.036.
*Hermanutz R. 1978. Endrin and malathion toxicity to flagfish (Jordanella floridae). Arch Environ
Contam Toxicol 7:159-168.
*Hermanutz RO, Eaton JG, Mueller LH. 1985. Toxicity of endrin and malathion mixtures to flagfish
(Jordanella floridae). Arch Environ Contam Toxicol 14:307-314.
*Hernandez JP, Mota LC, Baldwin WS. 2009. Activation of CAR and PXR by dietary, environmental
and occupational chemicals alters drug metabolism, intermediary metabolism, and cell proliferation.
Curr Pharmacogenomics Person Med 7(2):81-105.
*Hogmire HW, Weaver JE, Brooks JL. 1990. Survey for pesticides in wells associated with apple and
peach orchards in West Virginia. Bull Environ Contam Toxicol 44:81-86.
+*Hoogendam I, Versteeg JPJ, DeVlieger M. 1962. Electroencephalograms in insecticide toxicity. Arch
Environ Health 4:92-100.
+*Hoogendam I, Versteeg JPJ, DeVlieger M. 1965. Nine years’ toxicity control in insecticide plants.
Arch Environ Health 10:441-448
*Hopper M, King JW. 1991. Enhanced supercritical fluid carbon dioxide extraction of pesticides from
foods using pelletized diatomaceous earth. J Assoc Off Anal Chem 74(4):661-666.
*Howard PH. 1991. Handbook of environmental fate and exposure data for organic chemicals. Vol 3:
Pesticides. Chelsea, MI: Lewis Publishers, 349-361.
*HSDB. 1995. Hazardous Substances Data Bank. Bethesda, MD: National Library of Medicine,
National Toxicology Program (via TOXNET). November 1995.
*Hundley HK, Cairns T, Luke MA, et al. 1988. Pesticide residue findings by the Luke method in
domestic and imported foods and animal feeds for fiscal years 1982-1986. J Assoc Off Anal Chem
71(5):875-892.
*Hunter J, Maxwell JD, Stewart DA, et al. 1972. Increased hepatic microsomal enzyme activity from
occupational exposure to certain organochlorine pesticides. Nature 237:399-401.
*Hutson DH. 1981. The metabolism of insecticides in man. Prog Pestic Biochem 1:247-285.
*Hutson DH, Baldwin MK, Hoadley EC. 1975. Detoxication and bioactivation of endrin in the rat.
Xenobiotica 5:697-714.
*IARC. 1974. IARC monographs on the evaluation of carcinogenic risk of chemicals to man: Some
organochlorine pesticides. Vol 5. Lyon, France: World Health Organization.
*IARC. 1987. Endrin. In: IARC Monographs on the evaluation of carcinogenic risks to humans.
Supplement 7. Overall evaluations of carcinogenicity: An updating of IARC Monographs Volumes

ENDRIN 133
8. REFERENCES
1 to 42. Lyon, France: International Agency for Research on Cancer.

http://monographs.iarc.fr/ENG/Monographs/suppl7/Suppl7.pdf. November 15, 2017.
*IRIS. 2002. Endrin. Integrated Risk Information System. Chemical assessment summary.
Washington, DC: U.S. Environmental Protection Agency.
https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0363_summary.pdf. November 15,
2017.
*IRPTC. 1985. Treatment and disposal methods for waste chemicals. International Register of
Potentially Toxic Chemicals. Geneva, Switzerland: United Nations Environment Programme.
December 1985.
IRPTC. 1989. IRPTC data profile on endrin. International Register of Potentially Toxic Chemicals,
Geneva, Switzerland: United Nations Environment Programme. January 1989.
+*Jacobnizer H, Raybin HW. 1959. Briefs on accidental chemical poisonings in New York City.
Poisoning by insecticide (endrin). N Y State J Med:2017-2022.
*Janik F, Wolf HU. 1992. The Ca2+-transport-ATPase of human erythrocytes as an in vitro toxicity test
system--Acute effects of some chlorinated compounds. J Appl Toxicol 12:351-358.
*Jaquess AB, Winterlin W, Peterson D. 1989. Feasibility of toxaphene transport through sandy soil.
Bull Environ Contam Toxicol 42:417-423.
*Jarvinen AW, Tyo RM. 1978. Toxicity to fathead minnows of endrin in food and water. Arch Environ
Contam Toxicol 7:409-421.
*KAN-DO Office and Pesticides Team. 1995. Accumulated pesticides and industrial chemical findings
from a ten-year study of ready-to-eat foods. J AOAC Int 78(3):614-630.
Kanja LW, Skaare JU, Ojwang SBO, et al. 1992. A comparison of organochlorine pesticide residues in
maternal adipose tissue, maternal blood, cord blood, and human milk from mother/infant pairs. Arch
+*Kavlock RJ, Chernoff N, Hanisch RC, et al. 1981. Perinatal toxicity of endrin in rodents. II.
Fetotoxic effects of prenatal exposure in rats and mice. Toxicology 21:141-150.
+*Kavlock RJ, Chernoff N, Rogers EH. 1985. The effect of acute maternal toxicity on fetal development
in the mouse. Teratogen Carcinogen Mutagen 5:3-13.
*Kawamura Y, Sekita H, Sasaki K, et al. 1982. Analytical method for ethoprop (mocap) in agricultural
crops. J Food Hyg Soc Japan 23:81-85.
*Kenaga EE. 1980. Predicted bioconcentration factors and soil sorption coefficients of pesticides and
other chemicals. Ecotoxicol Environ Safety 4:26-38.
*Kennicutt MC, Wade BJ, Presley AG, et al. 1994. Sediment contaminants in Casco Bay, Maine:
Inventories, sources, and potential for biological impact. Environ Sci Technol 28(1):1-15.
*Keplinger ML, Deichmann WB. 1967. Acute toxicity of combinations of pesticides. Toxicol Appl
Pharmacol 10:586-595.
+*Kettering. 1969. Effects exerted upon beagle dogs during a period of two years by the introduction of
1,2,3,4,10,10-hexachloro-6,7- epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-endo, endo-5,8-
dimethanonaphthalene into their daily diets. Kettering Laboratory. Cincinnati, OH. Report to
Velsicol Chemical Corporation.
+*Kettering. 1971. The reproductive capacity among dogs fed diets containing endrin. Prepared by The
Kettering Laboratory in the Department of Environmental Health, College of Medicine, University
of Cincinnati for Velsicol Chemical Corp.
+*Kintz P, Baron L, Tracqui A, et al. 1992. A high endrin concentration in a fatal case. Forensic Sci Int
54(2):177-180.
*Klaasen CD, Amdur MD, Doull J. 1986. Casarett and Doull’s toxicology. 3rd ed. New York, NY:
MacMillan Publishing, 547-549.
*Klevay LM. 1971. Endrin excretion by the isolated perfused rat liver: A sexual difference. (35385)
Department of Environmental Health, University of Cincinnati, College of Medicine, Cincinnati,
OH.

ENDRIN 134
8. REFERENCES
*Knoevenagel K, Himmelreich R. 1976. Degradation of compounds containing carbon atoms by

photooxidation in the presence of water. Arch Environ Contam Toxicol 4:324-333.
*Kodavanti PRS, Mehrotra BD, Chetty SC, et al. 1988. Effect of selected insecticides on rat brain
synaptosomal adenylate cyclase and phospodiesterase. J Toxicol Environ Health 25:207-215.
*Korte F, Klein W, Weisgerber, et al. 1970. Recent results in studies on the fate of chlorinated
insecticides. Inter-American Conference on Toxic and Occupational Medicine, 6th Pesticides
Symposia, 51-56.
*Kraut-Vass A, Thoma J. 1991. Performance of an extraction disk in synthetic organic chemical analysis
using gas chromatograph-mass spectrometry. J Chromatogr 538:233-240.
*Krishnan K, Anderson ME, Clewell HJ, et al. 1994. Physiologically based pharmacokinetic modeling
of chemical mixtures. In: Yang RSH, ed. Toxicology of chemical mixtures. Case studies,
mechanisms, and novel approaches. San Diego, CA: Academic Press, 399-437.
*Kutz FW, Yobs AR, Yang HSC. 1976. National pesticide monitoring programs. In: Lee RE Jr., ed.
Air pollution from pesticides and agricultural processes. Cleveland, OH: CRC Press.
+*Lawrence CH, Coleman RL, Sowell WL. 1968. Endrin induced trace metal alterations following
acute exposure. Bull Environ Contam Toxicol 3(4):229-239. 10.1007/bf01684320.
*Leblanc GA. 1995. Trophic-level differences in the bioconcentration of chemicals: Implications in
assessing environmental biomagnification. Environ Sci Technol 29:154-160.
*Lee RF Jr. 1977. Fate of petroleum components in estuarine waters of the southeastern United States.
Proceedings of 1977 Oil Spill Conference: Prevention, behavior, control, cleanup, March 8-10,
1977. American Pesticide Institute, 611-616.
*Lee TP, Moscati R, Park BH. 1979. Effects of pesticides on human leukocyte functions. Res Comm
Chem Pathol Pharmacol 23(3):597-609.
*Lemaire G, de Sousa G, Rahmani R. 2004. A PXR reporter gene assay in a stable cell culture system:
CYP3A4 and CYP2B6 induction by pesticides. Biochem Pharmacol 68:2347-2358.
*Lemaire G, Mnif W, Mauvais P, et al. 2006. Activation of α- and β-estrogen receptors by persistent
pesticides in reporter cell lines. Life Sci 79(12):1160-1169. 10.1016/j.lfs.2006.03.023.
*Lewis RG, Lee RE. 1976. Air pollution from pesticides: Sources, occurrences and dispersions. In:
Lee RE, ed. Air pollution from pesticides and agricultural processes. Cleveland, OH: CRC Press.
*Ligocki MP, Pankow JF. 1985. Assessment of adsorption/solvent extraction with polyurethane foam
and adsorption/thermal desorption with Tenax-GC for the collection and analysis of ambient organic
vapors. Anal Chem 57:1138-1144.
*Ling Y-C, Huang I-P. 1995. Multiresidue matrix solid phase dispersion method for determining 16
organochlorine pesticides and polychlorinated biphenyls in fish. Chromatographia 40(5-6):259-266.
Long AR, Crouch MD, Barker SA. 1991b. Multiresidue matrix solid phase dispersion (MSPD)
extraction and gas chromatographic screening of nine chlorinated pesticides in catfish (Ictalurus
punctatus) muscle tissue. J Assoc Off Anal Chem 74:667-670.
*Long AR, Soliman MM, Barker SA. 1991. Matrix solid phase dispersion (MSPD) extraction and gas
chromatographic screening of nine chlorinated pesticides in beef fat. J Assoc Off Anal Chem
74:493-496.
*Lopez-Avila V, Bauer K, Milanes J, et al. 1993. Evaluation of Soxtec extraction procedure for
extracting organic compounds from soils and sediments. J AOAC Int 76:864-880.
*Lopez-Avila V, Dodhiwala NS, Becker WF. 1990. Supercritical fluid extraction and its application to
environmental analysis. J Chromatogr Sci 28:468-476.
*Lopez-Espinosa MJ, Granada A, Carreno J, et al. 2007. Organochlorine pesticides in placentas from
southern Spain and some related factors. Placenta 28(7):631-638. 10.1016/j.placenta.2006.09.009.
*Lott HM, Barker SA. 1993. Extraction and gas chromatographic screening of 14 chlorinated pesticides
in crayfish (Procambarus clarkii) hepatopancreas. J AOAC Int 76:663-668.
*Lowe JI. 1966. Some effects of endrin on estuarine fishes. In: Proceedings 19th Annual Conference of
Southeastern Association of Game and Fish Commissioners, 271-276.

ENDRIN 135
8. REFERENCES
*Ludke JL. 1976. Organochlorine pesticide residues associated with mortality: Additivity of chlordane
and endrin. Bull Environ Contam Toxicol 16:253-260.
Luke MA, Masumoto HT, Cairns T, et al. 1988. Levels and incidences of pesticide residues in various
foods and animal feeds analyzed by the Luke multiresidue methodology for fiscal year 1982-1986. J
Assoc Off Anal Chem 71:415-433.
*Lyman WJ. 1990. Handbook of chemical property estimation methods. Washington, DC: American
Chemical Society, 4-1-4-9.
*Marble LK, Delfino JJ. 1988. Extraction and solid phase cleanup methods for pesticides in sediment
and fish. Am Lab 23-32.
*Marsh JM. 1993. Assessment of nonpoint source pollution in stormwater runoff in Louisville,
(Jefferson County) Kentucky, USA. Arch Environ Contam Toxicol 25:446-455.
*Maslansky CJ, Williams GM. 1981. Evidence for an epigenetic mode of action in organochlorine
pesticide hepatocarcinogenicity: A lack of genotoxicity in rat, mouse, and hamster hepatocytes. J
Toxicol Environ Health 8:121-130.
*Mason JW, Rowe DR. 1976. The accumulation and loss of dieldrin and endrin in the eastern oyster.
Arch Environ Contam Toxicol 4:349-360.
*Mathews TD. 1994. Contaminants in recreationally important estuarine finfish from South Carolina.
Bull Environ Contam Toxicol 53:412-419.
*Maule A, Plyte S, Quirk V. 1987. Dehalogenation of organochlorine insecticides by mixed anaerobic
microbial populations. Pestic Biochem Physiol 27:229-236.
*McGregor DB, Brown AG, Howgate S, et al. 1991. Responses of the L5178Y mouse lymphoma cell
forward mutation assay V: 27 Coded chemicals. Environ Mol Mutagen 17:196-219.
*Meena K, Gupta PK, Bawa SR. 1978. Endrin-induced toxicity in normal and irradiated rats. Environ
Res 16:373-382.
+*Mehrotra BD, Moorthy KS, Ravichandra R, et al. 1989. Effects of cyclodiene compounds on calcium
pump activity in rat brain and heart. Toxicology 54:17-29.
*Merck Index. 1989. Merck index: An encyclopedia of chemicals, drugs, and biologicals. 11th ed.
Budavari S, ed. Rahway NJ: Merck & Co., Inc.
*Mersch-Sundermann V, Schneider U, Klopman G, et al. 1994. SOS induction in Escherichia coli and
Salmonella mutagenicity: A comparison using 330 compounds. Mutagenesis 9(3):205-224.
Mes J, Davies DJ, Turon D, et al. 1986. Levels and trends of chlorinated hydrocarbon contaminants in
the breast milk of Canadian women. Food Addit Contam 3:313-322.
Mes J, Doyle JA, Adams BR, et al. 1984. Polychlorinated biphenyls and organochlorine pesticides in
milk and blood of Canadian women during lactation. Arch Environ Contam Toxicol 13:217-223.
*Metcalf RL, Kapoor IP, Lu P-Y, et al. 1973. Model ecosystem studies of the environmental fate of six
organochlorine pesticides. Environ Health Perspect June:35-44.
Michael LC, Pellizari ED, Wiseman RW. 1988. Development and evaluation of a procedure for
determining volatile organics in water. Environ Sci Technol 22:565-570.
+*Miller PE, Fink GB. 1973. Brain serotonin level and pentylenetetrazol seizure threshold in dieldrin
and endrin treated mice. Proc West Pharmacol Soc 16:195-197.
*Minyard JP Jr, Roberts WE. 1991. State findings on pesticide residues in foods--1988 and 1989. J
Assoc Off Anal Chem 74:438-452.
*Molto JC, Lejeune B, Prognon P, et al. 1994. GC-MS determination of organochlorine pesticide in five
medicine plants. Int J Environ Anal Chem 54:81-91.
+*Moriya F, Hashimoto Y. 1999. Comparative studies on tissue distributions of organophosphorus,
carbamate and organochlorine pesticides in decedents intoxicated with these chemicals. J Forensic
Sci 44(6):1131-1135.
*Moriya M, Ohta T, Watanabe K, et al. 1983. Further mutagenicity studies on pesticides in bacterial
reversion assay systems. Mutat Res 116:185-216.
Moser GJ, Smart RC. 1989. Hepatic tumor-promoting chlorinated hydrocarbon stimulate protein kinase
C activity. Carcinogenesis 10(5):851-856.

ENDRIN 136
8. REFERENCES
*Mount DI, Putnicki GJ. 1966. Summary report of 1963 Mississippi fish kill. In: Trefethen JB, ed.
Transactions of the thirty-first North American wildlife and natural resources conference.
Washington, DC: Wildlife Management Institute, 177-184.
*Mumtaz MM, Tully DB, El-Masri HA, et al. 2002. Gene induction studies and toxicity of chemical
mixtures. Environ Health Perspect 110(Suppl 6):947-956.
Murayama J-I, Ishiwata M, Fukui M, et al. 1990. Comparative acute cytotoxicities of 37 xenobiotics
detected in drinking water to rat hepatocyte primary culture. Eisei Kagaku 36(4):267-276.
*Murray HE, Beck JN. 1990. Concentrations of selected chlorinated pesticides in shrimp collected from
the Calcasieu River/Lake complex, Louisiana. Bull Environ Contam Toxicol 44:798-804.
Mussalo-Rauhamaa H, Hasanen E, Pyysalo H, et al. 1990. Occurrence of beta-hexachlorocyclohexane in
breast cancer patients. Cancer 66(10):2124-2128.
+Nagelsmit A, van Vliet PW, van der Wiel-Wetzels WAM, et al. 1979. Porphyrins as possible
parameters for exposure to hexachlorocyclopentadiene, allylchloride, epichlorohydrin and endrin.
In: Strik JJTWA, Koeman JH, eds. Chemical porphyria in man. Amsterdam: Elsevier/North
Holland Biomedical Press, 55-61.
*Nakamura Y, Tonogai Y, Sekiguchi Y, et al. 1994. Multiresidue analysis of 48 pesticides in
agricultural products by capillary gas chromatography. J Agric Food Chem 42(11):2508-2518.
*Narahashi T. 1991. Transmitter-activated ion channels as the target of chemical agents. Adv Exp Med
Biol 287:61-72.
NAS. 1977. Drinking water and health. Washington, DC: National Academy of Sciences, 556-568.
*NAS/NRC. 1989. Report of the oversight committee. Biologic markers in reproductive toxicology.
Washington, DC: National Academy of Sciences, National Research Council, National Academy
Press, 15-35.
*Nash RG. 1983. Comparative volatilization and dissipation rates of several pesticides from soil. J
Agric Food Chem 31:210-217.
*Nash RG. 1984. Extraction of pesticides from environmental samples by steam distillation. J Assoc
Off Anal Chem 67:199-203.
*Nash RG, Harris WG. 1973. Chlorinated hydrocarbon insecticide residues in crops and soil. J Environ
Qual 2:267-273.
*Nash RG, Woolson EA. 1967. Persistence of chlorinated hydrocarbon insecticides in soils. Science
157:924-927.
Nash RG, Wells MJ, Smith AE, et al. 1986. Pesticide residues in environmental samples. In: Zweig G,
Sherma J, eds. Analytical methods for pesticides and plant growth regulators. Vol 15. New York,
NY: Academic Press, 247-286.
NATICH. 1992. NATICH data base report of federal, state, and local air toxics activities. Research
Triangle Park, NC: U.S. Environmental Protection Agency, Office of Air Quality Planning and
Standards, National Air Toxics Information Clearinghouse. EPA453R92008.
+*NCI. 1978. Bioassay of technical-grade endrin for possible carcinogenicity. Bethesda, MD: National
Cancer Institute, Division of Cancer Cause and Prevention. NCI-CG-TR 12.
*NIOSH. 1990. NIOSH pocket guide to chemical hazards. Washington, DC: US. Department of
Health and Human Services, Public Health Service, Centers for Disease Control, National Institute
for Occupational Safety and Health.
*NIOSH. 1992. Recommendations for Occupational Safety and Health. Compendium of Policy
Documents and Statements. Cincinnati, OH: U.S. Department of Health and Human Services,
National Institute for Occupational Safety and Health.
*NIOSH. 1994. Endrin. Immediately Dangerous to Life or Health Concentrations (IDLH). Atlanta,
GA: National Institute for Occupational Safety and Health, Centers for Disease Control and
Prevention. https://www.cdc.gov/niosh/idlh/72208.html. November 15, 2017.
*NIOSH. 2016. Endrin. NIOSH pocket guide to chemical hazards. Atlanta, GA: National Institute for
Occupational Safety and Health, Centers for Disease Control and Prevention.
https://www.cdc.gov/niosh/npg/npgd0252.html. November 15, 2017.

ENDRIN 137
8. REFERENCES
*NLM. 1988. Chemline. Bethesda, MD: National Library of Medicine. December 1988.
*NTP. 2016. Report on carcinogens, Fourteenth edition. CASRN Index in MS Excel. Research
Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service, National
Toxicology Program. https://ntp.niehs.nih.gov/pubhealth/roc/index-1.html#P. March 1, 2017.
+*Numan IT, Hassan MQ, Stohs SJ. 1990a. Endrin-induced depletion of glutathione and inhibition of
glutathione peroxidase activity in rats. Gen Pharmacol 21(5):625-628.
+*Numan IT, Hassan MQ, Stohs SJ. 1990b. Protective effects of antioxidants against endrin-induced
lipid peroxidation, glutathione depletion, and lethality in rats. Arch Environ Contam Toxicol
19:302-306.
*Osaba L, Aguirre A, Alonso A, et al. 1999. Genotoxicity testing of six insecticides in two crosses of the
Drosophila wing spot test. Mutat Res 439(1):49-61.
OSHA. 1974. Air contaminants. Occupational Safety and Health Administration. Code of Federal
OSHA. 1989. Air contaminants. Occupational Safety and Health Administration. Code of Federal
*OSHA. 2016a. Subpart D - Occupational health and environment controls. Gases, vapors, fumes,
dusts, and mists. Code of Federal Regulations. Occupational Safety and Health Standards. 29 CFR
1926.55. https://www.gpo.gov/fdsys/pkg/CFR-2016-title29-vol8/pdf/CFR-2016-title29-vol8-
sec1926-55.pdf. March 6, 2017.
*OSHA. 2016b. Subpart Z - Toxic and hazardous substances. Air contaminants. Code of Federal
Regulations. Occupational Safety and Health Standards. 29 CFR 1910.1000.
https://www.gpo.gov/fdsys/pkg/CFR-2016-title29-vol6/pdf/CFR-2016-title29-vol6-sec1910-
1000.pdf. March 6, 2017.
*OSHA. 2017. Subpart Z - Toxic and hazardous substances. Air contaminants. Code of Federal
Regulations. Occupational Safety and Health Standards. 29 CFR 1915.1000.
https://www.gpo.gov/fdsys/pkg/CFR-2017-title29-vol7/pdf/CFR-2017-title29-vol7-sec1915-
1000.pdf. September 7, 2017.
*Osowski SL, Brewer LW, Baker OE, et al. 1995. The decline of mink in Georgia, North Carolina, and
South Carolina: The role of contaminants. Arch Environ Contam Toxicol 29:418-423.
OTA. 1990. Neurotoxicity: Identifying and controlling poisons of the nervous system. Office of
Technology Assessment, Washington, DC. OTA-BA-438.
*Ottevanger CF, Van Sittert NJ. 1979. Relation between anti-12-hydroxy-endrin excretion and enzyme
induction in workers involved in the manufacture of endrin. In: Strik JJ, Koeman JH, eds.,
Chemical porphyria in man. Amsterdam: Elsevier/North-Holland Biomedical Press, 123-129.
+*Ottolenghi AD, Haseman JK, Suggs F. 1974. Teratogenic effects of aldrin, dieldrin, and endrin in
hamsters and mice. Teratology 9:11-16.
+*Pandey BB. 1978. A note on endrin poisoning in bullocks. Indian Vet J 55:253.
*Parkinson RW, Wang TC, White JR, et al. 1993. Distribution and migration of pesticide residues in
mosquito control impoundments. St. Lucie County, Florida, USA. Environ Geol 22:26-32.
*Patil KC, Matsumura F, Boush GM. 1970. Degradation of endrin, aldrin, and DDT by soil
microorganisms. Appl Microbiol 19:879-881.
*Patil KC, Matsumura F, Boush GM. 1972. Metabolic transformation of DDT, dieldrin, aldrin, and
endrin by marine microorganisms. Environ Sci Technol 6:629-632.
Pawar SS, Kachole MS. 1978. Hepatic and renal microsomal electron transport reactions in endrin
treated female guinea pigs. Bull Environ Contam Toxicol 20:199-205.
Petrella VJ, Fox JP, Webb RE. 1975. Endrin metabolism in endrin-susceptible and resistant strains of
pine mice. Toxicol Appl Pharmacol 34:283-291.
*Petrella VJ, McKinney JD, Fox JP, et al. 1977. Identification of metabolites of endrin. Metabolism in
endrin susceptible and resistant strains of pine mice. J Agric Food Chem 25(2):393-398.

ENDRIN 138
8. REFERENCES
*Petty JD, Huckins JN, Martin DB. 1995. Use of semipermeable membrane devices (SPMDS) to
determine bioavailable organochlorine pesticide residues in streams receiving irrigation drainwater.
Chemosphere 30(10):1891-1903.
+*Phillips DD, Pollard GE, Soloway SB. 1962. Thermal isomerization of endrin and its behavior in gas
chromatography. J Agric Food Chem 10(3):217-221.
+*Pi N, Chia SE, Ong CN, et al. 2016. Associations of serum organohalogen levels and prostate cancer
risk: Results from a case-control study in Singapore. Chemosphere 144:1505-1512.
10.1016/j.chemosphere.2015.10.020.
+*Piccoli C, Cremonese C, Koifman RJ, et al. 2016. Pesticide exposure and thyroid function in an
agricultural population in Brazil. Environ Res 151:389-398. 10.1016/j.envres.2016.08.011.
*Plumb RH. 1987. A comparison of ground water monitoring data from CERCLA and RCRA sites.
GWMR 7:94-100.
*Polanco Rodriguez AG, Inmaculada Riba Lopez M, Angel DelValls Casillas T, et al. 2017. Levels of
persistent organic pollutants in breast milk of Maya women in Yucatan, Mexico. Environ Monit
Assess 89(2):59-64. http://doi.org/10.1007/s10661-017-5768-y.
*Pontecorvo G, Fantaccione S. 2006. Recombinogenic activity of 10 chemical compounds in male germ
cells of Drosophila melanogaster. Ecotoxicol Environ Saf 65(1):93-101.
10.1016/j.ecoenv.2005.05.022.
*Prapamontol T, Stevenson D. 1991. Rapid method for the determination of organochlorine pesticides in
milk. J Chromatogr 552:249-257.
*Probst GS, McMahon RE, Hill LE, et al. 1981. Chemically-induced unscheduled DNA synthesis in
primary rat hepatocyte cultures: A comparison with bacterial mutagenicity using 218 compounds.
Environ Mutagen 3:11-32.
*Proctor NH, Hughes JP, Fischman ML. 1988. Chemical hazards of the workplace. 2nd ed.
Philadelphia, PA: J.B. Lippincott Co.
+*Quick MP, Shaw IC, Manser PA. 1989. A surprising case of endrin poisoning in dogs. J Forensic Sci
Soc 29(5):331-338.
+*Ressang AA, Titus I, Andar RS, et al. 1959. Aldrin, dieldrin and endrin intoxication in cats.
Communicationes Veterinariae 2:71-88.
+*Reuber MD. 1978. Carcinomas, sarcomas and other lesions in Osborne-Mendel rats ingesting endrin.
Exp Cell Biol 46:129-145.
+*Ribbens PH. 1985. Mortality study of industrial workers exposed to aldrin, dieldrin and endrin. Int
Arch Occup Environ Health 56:75-79.
*Richardson A, Robinson J, Baldwin MK. 1970. Metabolism of endrin in the rat. Chem Ind 15:502-
503.
*Richardson LA, Lane JR, Gardner WS, et al. 1967. Relationship of dietary intake to concentration of
dieldrin and endrin in dogs. Bull Environ Contam Toxicol 2(4):207-219.
*Romero ML, Dorea JG, Granja AC. 2000. Concentrations of organochlorine pesticides in milk of
Nicaraguan mothers. Arch Environ Health 55(4):274-278. 10.1080/00039890009603418.
Rotenberg SA, Weinstein IB. 1991. Two polychlorinated hydrocarbons cause phospholipid-dependent
protein kinase C activation in vitro in the absence of calcium. Mol Carcinogen 4:477-481.
+*Rowley DL, Rab MA, Hardjotanojo W, et al. 1987. Convulsions caused by endrin poisoning in
Pakistan. Pediatrics 79:928-934.
*Roy RR, Albert RH, Wilson P, et al. 1995. U.S. Food and Drug Administration Pesticide Program:
Incidence level monitoring of domestic and imported pears and tomatoes. J AOAC Int 78(4):930-
940.
+*Roylance KJ, Jorgensen CD, Booth GM, et al. 1985. Effects of dietary endrin on reproduction of
mallard ducks (Anas platyrhynchos). Arch Environ Contam Toxicol 14:705-711.
RTECS. 1994. Registry of Toxic Effects of Chemical Substances (RTECS). National Institute for
Occupational Safety and Health (NIOSH). Computer database online.

ENDRIN 139
8. REFERENCES
+*Runhaar EA, Sangster B, Greve PA, et al. 1985. A case of fatal endrin poisoning. Hum Toxicol
4:241-247.
*Russo MV, Goretti G, Liberti A. 1993. Rapid determination of chlorinated pesticides using CN-bonded
cartridges followed by GC-ECD. Chromatographia 35:290-294.
*Saleh MA, Abou Zied M, El-Baroty G, et al. 1993. Gamma aminobutyric acid radioreceptor-assay, a
possible biomarker for human exposure to certain agrochemicals. J Environ Sci Health B28:687-
699.
+*Samra NM, Selim AA. 2009. Organochlorine pesticides concentrations in maternal serum and their
effects on umbilical cord serum pesticides concentrations, neonatal birth weight and gestational age.
Aust J Basic Appl Sci 3:1972-1983.
Sax NI, Lewis RJ Sr. 1987. Hawley’s condensed chemical dictionary. 11th ed. New York, NY: Van
Nostrand Reinhold Company, 462.
*Schaalan MF, Abdelraouf SM, Mohamed WA, et al. 2012. Correlation between maternal milk and
infant serum levels of chlorinated pesticides (CP) and the impact of elevated CP on bleeding
tendency and immune status in some infants in Egypt. J Immunotoxicol 9(1):15-24.
10.3109/1547691x.2011.606432.
*Schafer ML, Peeler JT, Gardner WS, et al. 1969. Pesticides in drinking water: Waters from the
Mississippi and Missouri Rivers. Environ Sci Technol 3:1261-1269.
*Schattenberg HJ III, Hsu J-P. 1992. Pesticide residue survey of produce from 1989 to 1991. J AOAC
Int 75(5):925-933.
Scheufler E, Rozman K. 1986. Industrial and environmental chemicals. In: Rozman K, Hanninen O,
eds. Gastrointestinal toxicology. Amsterdam: Elsevier, 404-405.
*Schimmel SC, Parrish PR, Hansen DJ, et al. 1975. Endrin: Effects on several estuarine organisms. In:
Proceedings 28th Annual Conference of Southeastern Association of Game and Fish Commissioners,
187-194.
*Schmitt CJ, Zajicek JL, Peterman PH. 1990. National contaminant biomonitoring program: Residues
of organochlorine chemicals in U.S. freshwater fish, 1976-1984. Arch Environ Contam Toxicol
19:748-781.
*Schmitt CJ, Zajicek JL, Ribick MA. 1985. National pesticide monitoring program: Residues of
organochlorine chemicals in freshwater fish, 1980-81. Arch Environ Contam Toxicol 14:225-260.
*Schneider JF, Schneider KR, Spiro SE, et al. 1991. Evaluation of gas chromatography/matrix isolation-
infrared spectroscopy for the quantitative analysis of environmental samples. Appl Spectrosc
45:566-571.
Seidenberg JM, Becker RA. 1987. A summary of the results of 55 chemicals screened for developmental
toxicity in mice. Teratog Carcinog Mutagen 7:17-28.
Seifert J. 1989. Teratogenesis of polychlorocycloalkane insecticides in chicken embryos resulting from
their interactions at the convulsant recognition sites of the GABA (pro)receptor complex. Bull
+Shara MA, Dickson PH, Bagchi D, et al. 1992. Excretion of formaldehyde, malondialdehyde,
acetaldehyde and acetone in the urine of rats in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin,
paraquat, endrin and carbon tetrachloride. J Chromatogr 576:221-233.
*Sharom MS, Miles JR, Harris CR, et al. 1980a. Behavior of 12 insecticides in soil and aqueous
suspensions of soil and sediment. Water Res 14:1095-1100.
*Sharom MS, Miles JR, Harris CR, et al. 1980b. Persistence of 12 insecticides in water. Water Res
14:1089-1093.
*Singh AJ, Renzi FP. 1993. Drug withdrawal syndromes. In: Viccellio P. Handbook of Medical
Toxicology. Boston, MA: Little Brown and Company, 631-635.
*Sittig M, ed. 1980. Pesticide manufacturing and toxic materials control encyclopedia. Park Ridge, NJ:
Noyes Data Corporation, 366-373.
*Sittig M. ed. 1994. Domestic drinking water. World wide limits for toxic and hazardous chemicals in
air, water, and soil. Park Ridge, NJ: Noyes Data Corporation, 338-339.

ENDRIN 140
8. REFERENCES
*Smith-Baker C, Saleh MA. 2011. Hair as a marker for pesticides exposure. J Environ Sci Health B
46(7):648-653. 10.1080/03601234.2012.597701.
*Snyder JL, Grob RL, McNally ME, et al. 1992. Comparison of supercritical fluid extraction with
classical sonication and soxhlet extractions for selected pesticides. Anal Chem 64:1940-1946.
*Sobti RC, Krishan A, Davies J. 1983. Cytokinetic and cytogentic effect of agricultural chemicals on
human lymphoid cells in vitro. II. Organochlorine pesticides. Arch Toxicol 52:221-231.
+*Speck LB, Maaske CA. 1958. The effects of chronic and acute exposure of rats to endrin. AMA Arch
Ind Health 18:268-272.
*Spicer PE, Kereu RK. 1993. Organochlorine insecticide residues in human breast milk: A survey of
lactating mothers from a remote area in Papua, New Guinea. Bull Environ Contam Toxicol 50:540-
546.
*SRC. 1994a. Henry’s Law Constant Program (HENRYWIN, version 2.50, serial H0142). Syracuse
Research Corporation. Chemical Hazard Assessment Division, Environmental Chemistry Center,
Syracuse, NY.
*SRC. 1994b. Aqueous Hydrolysis Rate Program (HYDROWIN, Version 2.50a, serial H0Y0126).
Syracuse Research Corporation. Chemical Hazard Assessment Division, Environmental Chemistry
Center, Syracuse, NY.
*SRC. 1995a. Atmospheric Oxidation Program (AOPWIN, Version 2.65, serial 0156). Syracuse
Research Corporation. Chemical Hazard Assessment Division, Environmental Chemistry Center,
Syracuse, NY.
*SRC. 1995b. Octanol-Water Partition Coefficient Program (KOWWIN, Version 2.37, Serial L0148).
Syracuse Research Corporation. Chemical Hazard Assessment Division, Environmental Chemistry
Center, Syracuse, NY.
*SRI. 1987. Directory of chemical producers: United States of America. Menlo Park, CA: SRI
International, 847.
SRI International. 1981. National screening program for organics in drinking water: Part II. Report to
U.S. Environmental Protection Agency, Office of Drinking Water, Washington, DC by SRI
International, Menlo Park, CA.
*Stalling DL, Tindle RC, Johnson JL. 1972. Cleanup of pesticide and polychlorinated biphenyl residues
in fish extracts by gel permeation chromatography. J Assoc Off Anal Chem 55:32.
*Stanley JS. 1986. Broad scan analysis of the FY82 national human adipose tissue survey specimens:
Volume I - executive summary. Washington, DC: U.S. Environmental Protection Agency, Office of
Toxic Substances. EPA560586037.
*Staples CA, Werner AF, Hoogheem TJ. 1985. Assessment of priority pollutant concentrations in the
United States using STORET database. Environ Toxicol Chem 4:131-142.
*Storm DL. 1994. Chemical monitoring of California’s public drinking water sources: Public exposures
and health impacts. In: Wang RGM, ed. Water contamination and health. New York, NY: Marcel
Dekker, Inc, 67-124.
*Strachan WMJ. 1988. Toxic contaminants in rainfall in Canada:1984. Environ Toxicol Chem 7:871-
877.
*Swann RL, Laskowski DA, McCall PJ, et al. 1983. A rapid method for the estimation of the
environmental parameters octanol/water partition coefficient, soil sorption constant, water to air
ratio, and water solubility. Res Rev 85:17-28.
*Tabak HH, Quave SA, Mashni CI, et al. 1981. Biodegradability studies with organic priority pollutant
compounds. J Water Pollut Control Fed 53:1503-1518.
*Takeuchi S, Matsuda T, Kobayashi S, et al. 2006. In vitro screening of 200 pesticides for agonistic
activity via mouse peroxisome proliferator-activated receptor (PPAR)α and PPARγ and quantitative
analysis of in vivo induction pathway. Toxicol Appl Pharmacol 217:235-244.
*Tang PH, Ho JS, Eichelberger JW. 1993. Determination of organic pollutants in reagent water by
liquid-solid extraction followed by supercritical fluid elution. J AOAC Int 76:72-82.

ENDRIN 141
8. REFERENCES
*Tatken RL, Lewis RJ Sr, eds. 1983. Registry of toxic effects of chemical substances. 1981-1982 ed.
Vol 2. Cincinnati, OH: U.S. Department of Health and Human Services, Public Health Service,
Centers for Disease Control, National Institute for Occupational Safety and Health.
*Teshke K, Kelly SJ, Wiens M, et al. 1993. Concentrations of organochlorine pesticides in the adipose
tissue of British Columbia. Can J Publ Health 84(3):192-196.
+*Tewari SN, Sharma IC. 1978. Study of the distribution of chlorinated organic pesticides in different
autopsy materials of human poisoning cases using TLC and UV spectrophotometric techniques.
Chemical Era 215-218.
*Thomas RG. 1982. Volatilization from water. Handbook of chemical property estimation methods, 15-
1-15-34.
*Thomas RG. 1990. Volatilization from water. Handbook of chemical property estimation methods, 15-
1-15-17.
TOMES. 1994. TOMES (Toxicology, Occupational Medicine and Environmental Series) electronic
database. Endrin; endrin metabolites. Micromedex, Inc. Vol. 78.
*Tomkins BA, Merriweather R, Jenkins RA. 1992. Determination of eight organochlorine pesticides at
low nanogram/liter concentrations in groundwater using filter disk extraction and gas
chromatography. J AOAC Int 75:1091-1099.
+*Treon JF, Cleveland FP, Cappel J. 1955. Toxicity of endrin for laboratory animals. J Agric Food
Chem 3:842-848.
TRI. 1991. Toxic chemical release inventory reporting form R and instructions. Revised 1990 version.
Section 313 of the Emergency Planning and Community Right-to-Know Act (Title III of the
Superfund Amendments and Reauthorization Act of 1986). Washington, DC: U.S. Environmental
Protection Agency, Office of Toxic Substances. EPA560491007.
*Trotter WJ. 1993. Pesticide residues in composited milk collected through the U.S. Pasteurized Milk
Network. J AOAC Int 76(6):1220-1225,
*Tully DB, Cox VT, Mumtaz MM, et al. 2000. Six high-priority organochlorine pesticides, either singly
or in combination, are nonestrogenic in transfected HeLa cells. Reprod Toxicol 14(2):95-102.
*Tyler-Schroeder DB. 1979. Use of the grass shrimp (Palaemonetes pugio) in a life-cycle toxicity test.
In: Marking LL, Kimerle RA, eds. Aquatic toxicology, ASTM STP 667. American Society for
Testing and Materials, 159-170.
*USDA. 1995. U.S. Department of Agriculture, National Agricultural Pesticide Impact Assessment
Program (NAPIAP), Reregistration Notification Network (RNN). 3(11):1-1, 1-4.
*Valkenburg CA, Munslow WD, Butler LC. 1989. Evaluation of modifications to extraction procedures
used in analysis of environmental samples from Superfund sites. J Assoc Off Anal Chem 72:602-
608.
*Vance BD, Drummond W. 1969. Biological concentration of pesticides by algae. J Am Water Works
Assoc 61:360-362.
*Veith GD, Kosian P. 1983. Estimating bioconcentration potential from octanol/water partition
coefficients. In: Mackay D, Paterson S, Eisenreich SJ, et al., eds. Physical behavior of PCBs in the
Great Lakes. Ann Arbor, MI: Ann Arbor Science Publishers, 269-282.
*Veith GD, Defoe DL, Bergstedt BV. 1979. Measuring and estimating the bioconcentration factor of
chemicals in fish. Environ Sci Technol 16(5):1040-1048.
Velsicol Chemical Corporation. 1969. MRID No. 00030198. Available from U.S. EPA. Write Freedom
of Information Office, U.S. Environmental Protection Agency, Washington, DC 20460.
*Venkat JA, Shami S, Davis K, et al. 1995. Relative genotoxic activities of pesticides evaluated by a
modified SOS microplate assay. Environ Mol Mutagen 25:67-76.
*Verschueren K. 1983. Handbook of environmental data on organic chemicals. 2nd ed. New York,
NY: Van Nostrand Reinhold Company, 606-611.
+*Versteeg JP, Jager KW. 1973. Long-term occupational exposure to the insecticides aldrin, dieldrin,
endrin, and telodrin. Br J Ind Med 30:201-202.

ENDRIN 142
8. REFERENCES
*Viana E, Molto JC, Manes J, et al. 1994. Clean up confirmatory procedures for gas chromatographic
analysis of pesticide residues, Part II. J Chromatogr 678(1):109-117.
*Vrij-Standhardt WC, Strik JJ, Ottevanger CF. 1979. Urinary D-glucaric acid and urinary total
porphyrin excretion in workers exposed to endrin. In: Strik JJ, Koeman JH, eds. Chemical
porphyria in man. Amsterdam: Elsevier/North Holland Biomedical Press, 113-121.
*Wafford KA, Sattelle DB, Gant DB, et al. 1989. Noncompetitive inhibition of GABA receptors in
insect and vertebrate CNS by endrin and lindane. Pestic Biochem Physiol 33:213-219.
Walker CH. 1981. The correlation between in vivo and in vitro metabolism of pesticides in vertebrates.
In: Hutson DH, Roberts TR, eds. The metabolism of insecticides in man. Prog Pestic Biochem
1:247-285.
Walker JJ, Philips DE. 1987. An electron microscopic study of endrin induced alterations in
unmyelinated fibers of mouse sciatic nerve. Neurotoxicology 8:55-64.
+*Waller K, Prendergast TJ, Slagle A, et al. 1992. Seizures after eating a snack food contaminated with
the pesticide endrin: The tale of the toxic taquitos. West J Med 157(6):648-651.
*Walters SM. 1986. Cleanup of samples. In: Zweig G, Sherma J, eds. Analytical methods for
pesticides and plant growth regulators, Vol. 15, Chapter 3. New York, NY: Academic Press, 67-
110.
+*Ward EM, Schulte P, Grajewski B, et al. 2000. Serum organochlorine levels and breast cancer: A
nested case-control study of Norwegian women. Cancer Epidemiol Biomarkers Prev 9(12):1357-
1367.
+*Webb RE, Hartgrove RW, Randolph WC, et al. 1973. Toxicity studies in endrin-susceptible and
resistant strains of pine mice. Toxicol Appl Pharmacol 25:42-47.
+*Weeks DE. 1967. Endrin food-poisoning: A report on four outbreaks caused by two separate
shipments of endrin-contaminated flour. Bull WHO 37:499-512.
*WHO. 2010. Guidelines for indoor air quality: Selected pollutants. Geneva, Switzerland: World
Health Organization. http://www.euro.who.int/__data/assets/pdf_file/0009/128169/e94535.pdf.
April 25, 2012.
*WHO. 2017. Guidelines for drinking-water quality. Fourth edition incorporating the first addendum.
Geneva, Switzerland: World Health Organization.
http://apps.who.int/iris/bitstream/10665/254637/1/9789241549950-eng.pdf?ua=1. February 28,
2017.
*Wieboldt RC, Adams GE, Later DW. 1988. Sensitivity improvement in infrared detection for
supercritical fluid chromatography. Anal Chem 60:2422-2427.
*Wigfield YY, Grant R. 1992. Evaluation of an immunoassay kit for the detection of certain
organochlorine (cyclodiene) pesticide residues in apple, tomato, and lettuce. Bull Environ Contam
Toxicol 49:342-347.
*Williams DT, LeBel GL, Junkins E. 1984. A comparison of organochlorine residues in human adipose
tissue autopsy samples from two Ontario municipalities. J Toxicol Environ Health 13:19-29.
*Williams DT, LeBel GL, Junkins E. 1988. Organohalogen residues in human adipose autopsy samples
from six Ontario municipalities. J Assoc Off Anal Chem 71(2):410-414.
*Williams GM. 1980. Classification of genotoxic and epigenetic hepatocarcinogens using liver culture
assays. Ann NY Acad Sci 349:273-282.
Williams GM, Mori H, McQueen CA. 1989. Structure-activity relationships in the rat hepatocyte DNA-
repair test for 300 chemicals. Mutat Res 221:263-286.
*Wnuk M, Kelley R, Breuer G, et al. 1987. Pesticides in water samples using surface water sources.
Des Moines, IA: Iowa Department of Natural Resources and Iowa University Hygienic Laboratory.
PB88136916.
*Wolfe HR, Durham WF, Armstrong JF. 1963. Health hazards of the pesticides endrin and dieldrin:
Hazards in some agricultural uses in the Pacific Northwest. Arch Environ Health 6:458-464.
*Woo OF. 1990. Chlorinated hydrocarbon pesticides in poisoning and drug overdose. Olson K, ed.
Norwalk, CT: Appleton & Lange, 117-118.

ENDRIN 143
8. REFERENCES
*Worthington CR, Walker SB. 1983. The Pesticide manual. The British Crop Protection Council. 7th
edition, 235.
*Yess NJ, Gunderson EL, Roy RR. 1993. U.S. Food and Drug Administration monitoring of pesticide
residues in infant foods and adult foods eaten by infants/children. J AOAC Int 76(3):492-507.
Yess NJ, Houston MG, Gunderson EL. 1991. Food and Drug Administration pesticide residue
monitoring of foods:1983-1986. J Assoc Off Anal Chem 74(2):273-280.
+*Young RA, Mehendale HM. 1986. Effect of endrin and endrin derivatives on hepatobiliary function
and carbon tetrachloride-induced hepatotoxicity in male and female rats. Food Chem Toxicol
24:863-868.
*Zabik MJ, Schuetz RD, Burton WL, et al. 1971. Photochemistry of bioactive compounds: Studies of a
major photolytic product of endrin. J Agric Food Chem 19:308-313.
Zavon MR, Hine CH, Parker KD. 1965. Chlorinated hydrocarbon insecticides in human body fat in the
United States. JAMA 193(10):837-839.
*Zeiger E, Anderson B, Haworth S, et al. 1987. Salmonella mutagenicity tests: III. Results from the
testing of 255 chemicals. Environ Mutagen 9:1-18.
*Zlatkis A, Kim K. 1976. Column elution and concentration of volatile compounds in biological fluids.
J Chromatogr A 126:475-485.

ENDRIN A-1
APPENDIX A. ATSDR MINIMAL RISK LEVEL WORKSHEETS
MRLs are derived when reliable and sufficient data exist to identify the target organ(s) of effect or the
most sensitive health effect(s) for a specific duration for a given route of exposure. An MRL is an
estimate of the daily human exposure to a hazardous substance that is likely to be without appreciable risk
of adverse noncancer health effects over a specified route and duration of exposure. MRLs are based on
noncancer health effects only; cancer effects are not considered. These substance-specific estimates,
which are intended to serve as screening levels, are used by ATSDR health assessors to identify
contaminants and potential health effects that may be of concern at hazardous waste sites. It is important
to note that MRLs are not intended to define clean-up or action levels.
MRLs are derived for hazardous substances using the NOAEL/uncertainty factor approach. They are
below levels that might cause adverse health effects in the people most sensitive to such chemical-
induced effects. MRLs are derived for acute (1–14 days), intermediate (15–364 days), and chronic
(≥365 days) durations and for the oral and inhalation routes of exposure. Currently, MRLs for the dermal
route of exposure are not derived because ATSDR has not yet identified a method suitable for this route
of exposure. MRLs are generally based on the most sensitive substance-induced endpoint considered to
be of relevance to humans. Serious health effects (such as irreparable damage to the liver or kidneys, or
birth defects) are not used as a basis for establishing MRLs. Exposure to a level above the MRL does not
mean that adverse health effects will occur.
MRLs are intended only to serve as a screening tool to help public health professionals decide where to
look more closely. They may also be viewed as a mechanism to identify those hazardous waste sites that
are not expected to cause adverse health effects. Most MRLs contain a degree of uncertainty because of
the lack of precise toxicological information on the people who might be most sensitive (e.g., infants,
elderly, nutritionally or immunologically compromised) to the effects of hazardous substances. ATSDR
uses a conservative (i.e., protective) approach to address this uncertainty consistent with the public health
principle of prevention. Although human data are preferred, MRLs often must be based on animal studies
because relevant human studies are lacking. In the absence of evidence to the contrary, ATSDR assumes
that humans are more sensitive to the effects of hazardous substance than animals and that certain persons
may be particularly sensitive. Thus, the resulting MRL may be as much as 100-fold below levels that
have been shown to be nontoxic in laboratory animals.

ENDRIN A-2
APPENDIX A
Proposed MRLs undergo a rigorous review process: Health Effects/MRL Workgroup reviews within the
Division of Toxicology and Human Health Sciences, expert panel peer reviews, and agency-wide MRL
Workgroup reviews, with participation from other federal agencies and comments from the public. They
are subject to change as new information becomes available concomitant with updating the toxicological
profiles. Thus, MRLs in the most recent toxicological profiles supersede previously published MRLs.
For additional information regarding MRLs, please contact the Division of Toxicology and Human
Health Sciences, Agency for Toxic Substances and Disease Registry, 1600 Clifton Road NE, Mailstop
S102-1, Atlanta, Georgia 30329-4027.

ENDRIN A-3
APPENDIX A
MINIMAL RISK LEVEL (MRL) WORKSHEET

Chemical Name: Endrin
CAS Numbers: 72-20-8
Date: August 1996
March 2017—Updated literature search
Profile Status: Final, Draft for Public Comment
Route: Inhalation
Duration: Acute
MRL Summary: There are insufficient data for derivation of an acute inhalation MRL.
Rationale for Not Deriving an MRL: The limited number of human studies available do not contain
quantitative data needed for MRL derivation and often report co-exposure to other chemicals (e.g., aldrin,
dieldrin). Acute inhalation data in laboratory animals are limited to one study reporting brain lesions and
mortality in a single cat exposed twice to endrin at 417 ppm (1 hour/session) (Ressang et al. 1959).
Agency Contacts (Chemical Manager): Susan Zells Ingber

ENDRIN A-4
APPENDIX A

Date: August 1996
Route: Inhalation
Duration: Intermediate
MRL Summary: There are insufficient data for derivation of an intermediate-duration inhalation MRL.
dieldrin). The intermediate-duration inhalation database in laboratory animals consists of a single study
evaluating survival in cats, guinea pigs, hamsters, rats, rabbits, and mice exposed to endrin at 0.36 ppm
for 107–130 days (5 days/week, 7 hours/day) (Treon et al. 1955). Necropsy was only performed on
animals that died (1/3 mice, 2/4 rabbits), and no controls were used.

ENDRIN A-5
APPENDIX A

Date: August 1996
Route: Inhalation
Duration: Chronic
MRL Summary: There are insufficient data for derivation of a chronic-duration inhalation MRL.
dieldrin). No chronic-duration inhalation studies in laboratory animals were identified for endrin.

ENDRIN A-6
APPENDIX A

Date: May 2019
Route: Oral
Duration: Acute
MRL 0.0006 mg/kg/day (provisional)
Critical Effect: Decreased locomotor activity
Reference: Kavlock et al. 1981
Point of Departure: BMDL1SD of 0.06 mg/kg/day
Uncertainty Factor: 100
LSE Graph Key: 13
Species: Rat
MRL Summary: A provisional acute-duration oral MRL of 0.0006 mg/kg/day was derived for endrin
based on evidence of neurotoxicity (decreased locomotor activity) in rats following a single exposure to
endrin at gavage doses ≥0.5 mg/kg (Kavlock et al. 1981). The provisional MRL is based on the
BMDL1SD of 0.06 mg/kg for depressed locomotor activity and a total uncertainty factor of 100 (10 for
extrapolation from animals to humans and 10 for human variability).
Selection of the Critical Effect: The lowest LOAELs identified in the acute oral database include a
serious LOAEL of 0.3 mg/kg/day for a 38% decrease in maternal body weight gain in rats exposed to
endrin for 14 days during gestation (Kavlock et al. 1981), a LOAEL of 0.5 mg/kg/day for decreased
locomotion in female rats on day 1 of a 14-day exposure (Kavlock et al. 1981), and a LOAEL of
0.5 mg/kg/day for increased liver weights in maternal rats exposed to endrin for 11 days during gestation
(Kavlock et al. 1981). A NOAEL of 0.15 mg/kg/day was established for maternal body weight effects; no
NOAELs were identified for neurological or hepatic effects in the Kavlock et al. (1981) study. Other
reported body weight, neurological, and hepatic effects following acute exposure to endrin are reviewed
in Table A-1. Observed effects in other systems, including the developing fetus, occurred at doses
≥1 mg/kg (see Table 2-3), and were not considered as candidate critical effects. It should be noted that
increased mortality occurred in female CD rats exposed to ≥0.5 mg/kg/day for up to 14 days (Kavlock et
al. 1981); however, the same authors observed 100% survival in a second study of female CD rats
exposed to doses up to 0.45 mg/kg/day for 14 days (Kavlock et al. 1981). In other rat strains and other
species, reported lethal doses following acute exposure were ≥1.5 mg/kg (see Table 2-3).
Since decreased maternal body weight in rats, decreased locomotion in female rats, and increased
maternal liver weight in mice occurred at similar doses in the various experiments conducted by Kavlock
et al. (1981), all were considered for provisional MRL derivation.
Table A-1. Summary of Candidate Critical Effects for Provisional Acute Oral
MRL for Endrin
Duration NOAEL LOAEL

Species (route) (mg/kg/day) (mg/kg/day) Effect Reference
Neurological effects
CD rat 14 days ND 0.5 Depressed locomotor Kavlock et al.
(GO) activity on day 1 1981
(range-finding)

ENDRIN A-7
APPENDIX A
MRL for Endrin

Holtzman albino rat 8 days, 1 ND No clinical signs of Coleman et al.
every 2– neurotoxicity 1968
3 days (GO)
Holtzman albino rat Once ND 25 Convulsions Lawrence et al.
(GO) (serious 1968
LOAEL)
CD-1 mouse Up to 0.5 1.5 Decreased locomotor Kavlock et al.
11 days activity on days 1 and 3 1981
(range-finding)
Golden Syrian Once 7.5 10 Convulsions Chernoff et al.
hamster GD 8 (serious 1979a
(GO) LOAEL)
Hepatic effects
CD rat 14 days 0.45 No change in maternal Kavlock et al.
GDs 7–20 liver weight 1981
(GO) (main study)
CD-1 mouse 11 days ND 0.5 Increased relative Kavlock et al.
GDs 7–17 maternal liver weight 1981
(GO) (main study)
Holtzman albino rat 8 days, 1 (TWA) ND No change in liver Coleman et al.
every 2– weight 1968
3 days
Sprague-Dawley rat Once ND 3 Increased relative liver Bagchi et al.
(GO) weight 1992a, 1992b,
1992c
Golden Syrian 10 days 3.5 ND No change in liver Chernoff et al.
hamster GDs 5–14 weight 1979a
(GO)
Sprague-Dawley rat Once 4 ND No change in liver Numan et al.
(GO) weight 1990a
Sprague-Dawley rat; Once ND 4 Necrosis, fatty Hassan et al.
Swiss Webster (GO) degeneration, 1991
mouse; guinea pig; inflammation, cell
golden Syrian regeneration, lipid
hamster peroxidation
Sprague-Dawley rat 1–2 days 8.2 Altered serum Ali and
(F) chemistry, Shakoori 1993
vacuolization, fatty
infiltration
Body weight effects
CD rat 14 days 0.15 0.3 38% decrease in Kavlock et al.
GDs 7–20 (serious maternal body weight 1981
(GO) LOAEL) gain (main study)

ENDRIN A-8
APPENDIX A
MRL for Endrin

Sherman rat 10 days 0.5 2 12% decrease in Goldenthal et
GDs 6–15 maternal weight gain al. 1978a
(G) (2/25 dams died at this
dose)
CD-1 mouse 11 days 0.5 1 24% decrease in Kavlock et al.
GDs 7–17 (serious maternal body weight 1981
(GO) LOAEL) gain (main study)
CD-1 mouse 11 days 0.5 1.5 43% decrease in body Kavlock et al.
(GO) (serious weight gain 1981
LOAEL) (range-finding)
Golden Syrian 10 days ND 1.5 19-fold increase in Chernoff et a.
hamster GDs 5–14 (serious weight loss (37% 1979a)
(GO) LOAEL) mortality rate at this
dose)
C57BL/6J or DBA/2J Once 6 ND No change in body Hassoun and
mouse GD 12 weight in surviving Stohs 1996a
(GO) dams (25% mortality at
6 mg/kg)
Sprague-Dawley rat 1–2 days 8.2 Ali and
(F) Shakoori 1993
F = feed; GD = gestation day; GO = gavage-oil; LOAEL = lowest observed adverse effect level; MRL = minimal risk
level; ND = not determined; NOAEL = no-observed-adverse-effect level; TWA = time-weighted average
Selection of the Point of Departure and Principal Study: In order to identify the study providing the
most sensitive POD, BMD modeling was attempted for the most sensitive data for each critical endpoint
identified in Table A-1. The data were fit to all continuous models in EPA’s Benchmark Dose Software
(BMDS, version 2.6.0) using a benchmark response (BMR) of 1 standard deviation (locomotor activity)
or 10% relative deviation (body and organ weight data). Adequate model fit was judged by three criteria:
goodness-of-fit statistics (p-value >0.1), visual inspection of the dose-response curve, and scaled residual
at the data point (except the control) closest to the predefined BMR. Among all of the models providing
adequate fit to the data, the lowest BMDL (95% lower confidence limit on the BMD) was selected as the
POD when the difference between the BMDLs estimated from these models was >3-fold; otherwise, the
BMDL from the model with the lowest Akaike Information Criterion (AIC) was chosen. Suitable models
were identified for neurological and liver weight data sets; see values in Table A-2. No suitable models
were identified for the maternal body weight data, whether using the full data set or dropping the highest
dose. Therefore, ATSDR used the NOAEL/LOAEL approach for this endpoint. The datasets used for
BMD modeling are presented in Tables A-3 and A-4. The model predictions (Tables A-5 and A-6) and
the fits of the selected models (Figures A-1 and A-2) are presented at the end of this worksheet.
The candidate PODs are summarized in Table A-2. Neurological effects in female rats (0.08 mg/kg/day)
had the lowest effect level (BMD or LOAEL); therefore, the resulting BMDL of 0.06 mg/kg/day for
neurological effects was selected as the POD for the provisional MRL. This POD is 5 times lower than
the LOAEL for decreased maternal body weight gain and nearly 10 times lower than the lethal dose
reported in the range-finding study by Kavlock et al. (1981). Furthermore, the central nervous system is

ENDRIN A-9
APPENDIX A
the primary target system for endrin toxicity (see Section 2.15 and Other Additional Studies or Pertinent
Information below).
Table A-2. Summary of Candidate Critical Effects and PODs for the Provisional
Acute Oral MRL for Endrin
Duration/ NOAEL LOAEL BMD BMDL

Species route (mg/kg/day) (mg/kg/day) (mg/kg/day) (mg/kg/day) Effect Reference
CD rat 14 days ND 0.5 0.08 0.06a Decreased Kavlock et
(GO) (BMD1SD) (BMDL1SD) locomotor al. 1981
activity on
day 1
Hepatic effects
CD-1 11 days ND 0.5 1.06 0.69 Increased Kavlock et
mouse GDs 7–17 (BMDRD10) (BMDLRD10) relative al. 1981
(GO) liver weight
in dams
Body weight effects
CD rat 14 days 0.15 0.3 NA NA 38% Kavlock et
GDs 7–20 (serious decrease al. 1981
(GO) LOAEL) in maternal
body
weight gain
aSelected POD.
BMD = maximum likelihood estimate of the dose associated with the selected benchmark response; BMDL = 95%
lower confidence limit on the BMD (subscripts denote benchmark response: 1 SD = exposure level associated with
1 standard deviation in response; RD10 = exposure level associated with a 10% change in outcome);
GD = gestation day; GO = gavage (oil vehicle); LOAEL = lowest observed adverse effect level; NA = not applicable
(no adequate model fit); NOAEL = no-observed-adverse-effect level; POD = point of departure
Table A-3. Locomotor Activity in Female Rats Following a Single Gavage

Administration of Endrin
Dose (mg/kg)
0 0.5 1.0 2.0
Locomotor activity (number of photocell beam interruptions) 665±82 400±33 186±49 83±51
Mean±SD (N) (6) (5) (6) (4)
N = number; SD = standard deviation
Source: Kavlock et al. 1981

ENDRIN A-10
APPENDIX A
Table A-4. Relative Liver Weight in Mouse Dams Following Gavage

Administration of Endrin on GDs 7–17
Dose (mg/kg/day)
0 0.5 1.0 1.5 2.0
Relative maternal liver weight (%) 6.7±1.0 7.2±0.6 7.4±0.6 8.1±0.7 7.2±NR
Mean±SD (N) (27) (31) (32) (12) (2)
N = number; NR = not reported (no variance data reported by study authors); SD = standard deviation (SD
calculated for this review from reported standard error of the mean and animal number)
Source: Kavlock et al. 1981
Summary of the Principal Study:
Kavlock RJ, Chemoff N, Hanisch RC, et al. 1981. Perinatal toxicity of endrin in rodents. II. Fetotoxic
effects of prenatal exposure in rats and mice. Toxicology 21:141-150.
Kavlock et al. (1981) conducted two studies in CD rats, a preliminary range-finding study in nonpregnant
females and a main teratology study in pregnant females.
Range-Finding Study. In the range finding study, groups of 5–9 nonpregnant female rats were
administered doses of 0, 0.5, 1.0, 2.0, and 4.0 mg/kg/day endrin (>99% pure) via gavage in corn oil for up
to 14 days. This preliminary range-finding study only evaluated mortality, body weight, and locomotor
activity. Reactive locomotor activity was measured for 30 minutes on day 1 in figure-eight mazes (2–
4 hours after initial dosing).
Increased mortality occurred in all treated groups, with 60% mortality at 0.5 mg/kg/day and 100%
mortality at higher doses. Survival time decreased in a time-related manner. Average time-to-death at
0.5, 1.0, 2.0, and 4.0 mg/kg/day was 7.7, 5.5, 3.4, and 1.3 days, respectively. All control animals
survived. Body weight gain in the two surviving rats at the lowest dose was decreased 94% compared to
controls (1.8 g gained versus 32.4 g gained). Two of the six animals in the 4 mg/kg exposure group
experienced convulsions within 2–4 hours of the first exposure; these animals were excluded from the
locomotor activity assessment. In other treated animals, a dose-related decrease in locomotor activity was
observed 2–4 hours after the first administration. Activity was significantly depressed by 40, 72, and
88% at 0.5, 1.0, and 2.0 mg/kg, respectively. The study authors reported that activity was also decreased
by 88% in the four rats at 4 mg/kg/day that did not experience convulsions; however, statistics and
quantitative data for this group were not reported.
Main Teratology Study. Based on findings from the range-finding study, groups of 15–32 pregnant
female rats were administered doses of 0, 0.075, 0.15, 0.03, and 0.45 mg/kg/day via gavage in corn oil
from GD 7 to 20. Dams were observed for mortality and maternal body weight gain was monitored. All
dams were sacrificed on GD 21. At sacrifice, the uterus and liver were removed and weighed. The uterus
was examined for the number of live, dead, and resorbed fetuses. The fetuses were weighed, examined
for gross anomalies, and divided equally for examination for skeletal and visceral malformations and
variations.
Despite 60% mortality at 0.5 mg/kg/day in the range-finding study, no mortalities occurred in the main
study at doses up to 0.45 mg/kg/day (highest dose tested). The study authors did not discuss potential
reasons for this apparent steep dose-response curve for lethality. However, results from the main study

ENDRIN A-11
APPENDIX A
are consistent with findings in other rat strains, which only reported increased mortality after exposure to
acute doses ≥2 mg/kg/day (Bedford et al. 1975a; Gaines 1960, 1969; Goldenthal et al. 1978a; Numan et
al. 1990b; Speck and Maaske 1958; Treon et al. 1955). Maternal body weight gain was significantly
decreased by 38–87% at ≥0.3 mg/kg/day. No exposure-related changes were observed in maternal liver
weight. There were exposure-related changes in fetal endpoints.
Uncertainty Factor: The BMDL1SD is divided by a total uncertainty factor of 100:

• 10 for extrapolation from animals to humans
• 10 for human variability
Provisional MRL = BMDL1SD ÷ uncertainty factors

0.06 mg/kg/day ÷ (10x10) = 0.0006 mg/kg/day
Other Additional Studies or Pertinent Information: The POD based on neurological effects (BMDL of
0.06 mg/kg/day) is 5 times lower than the LOAEL for decreased maternal body weight gain and nearly
10 times lower than the lethal dose reported in the range-finding study by Kavlock et al. (1981), resulting
in an MRL that is 500–1,000 times lower than any doses associated with adverse health effects or
mortality. Therefore, the MRL based on neurological effects is protective of other known endpoints.
Identification of neurotoxicity as the critical effect of endrin is supported by reports of neurologic effects
including convulsions and tremors in humans acutely poisoned with endrin (Carbajal-Rodriquez et al.
1990; Coble et al. 1967; Curley et al. 1970; Davies and Lewis 1956; Rowley et al. 1987; Waller et al.
1992; Weeks 1967) and various animal species following oral exposure (Chernoff et al. 1979a;
Deichmann et al. 1970; Kavlock et al. 1981; Kettering 1969; Mehrotra et al. 1989; Treon et al. 1955).
Acute neurotoxic effects have also been observed following high occupational exposure (Hoogendam et
al. 1962, 1965). There is also limited animal evidence for neurotoxicity following acute inhalation or
dermal exposure (Gaines 1960; Pandy 1978; Ressang et al. 1959; Treon et al. 1955).

ENDRIN A-12
APPENDIX A
Table A-5. Model Predictions for Locomotor Activity in Female Rats Following a
Single Gavage Administration of Endrin (Kavlock et al. 1981)
c
Test for Scaled residuals
significant Means Dose Dose
difference Variance p- below above Overall BMD1SD BMDL1SD
Model p-valuea p-valueb valueb BMD BMD largest AIC (mg/kg) (mg/kg)
Constant variance
Exponential <0.0001 0.19 0.2614 -0.200 0.978 -1.092 196.0 0.08 0.06
(model 2)d,e
Exponential <0.0001 0.19 0.1243 -0.087 0.585 1.007 197.7 0.09 0.06
(model 3)d
Exponential <0.0001 0.19 0.1035 -0.229 1.041 -1.079 198.0 0.07 0.05
(model 4)d
Exponential <0.0001 0.19 NA 5.38x10-8 8.10x10-8 2.58x10-7 197.3 NA NA
(model 5)d
Hilld <0.0001 0.19 NA -1.18x10-6 2.1x10-7 -1.18x10-6 197.3 NA NA
Linearf <0.0001 0.19 <0.0001 1.93 -0.903 -2.63 219.3 NA NA
Polynomial <0.0001 0.19 <0.0001 1.93 -0.903 -2.63 219.3 NA NA
(2-degree)f
Polynomial <0.0001 0.19 <0.0001 1.93 -0.903 -2.63 219.3 NA NA
(3-degree)f
Powerd <0.0001 0.19 <0.0001 1.93 -0.903 -2.63 219.3 NA NA
aValues >0.05 fail to meet conventional goodness-of-fit criteria.
bValues <0.10 fail to meet conventional goodness-of-fit criteria.
cScaled residuals at doses immediately below and above the benchmark dose; also the largest residual at any dose.
dPower restricted to ≥1.
eSelected model. Constant variance models provided adequate fit to the variance data. With constant variance
model applied, only Exponential model 2, model 3, and model 4 provided adequate fit to the means. BMDLs for
models providing adequate fit were sufficiently close (differed by <2–3-fold), so the model with the lowest AIC is
preferred (Exponential model 2).
fCoefficients restricted to be negative.
AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the exposure concentration associated
with the selected benchmark response; BMDL = 95% lower confidence limit on the BMD (subscripts denote
benchmark response: i.e., 1SD = exposure concentration associated with 1 standard deviation change in outcome);
NA = not applicable (BMDL computation failed or model did not provide adequate fit to the data); SD = standard
deviation

ENDRIN A-13
APPENDIX A
Figure A-1. Fit of Exponential Model 2 to Data for Locomotor Activity (Number of
Photocell Beam Interruptions) in Female Rats Following a Single Gavage
Administration of Endrin (Kavlock et al. 1981)
Exponential 2 Model, with BMR of 1 Std. Dev. for the BMD and 0.95 Lower Confidence Limit for the BMDL
800 Exponential 2
700
600
500
Mean Response
400
300
200
100
BMDL BMD
0 0.5 1 1.5 2
dose
22:11 01/17 2018

ENDRIN A-14
APPENDIX A
Table A-6. Model Predictions for Maternal Relative Liver Weight in Female Mice
Following Gavage Administration of Endrin from GD 7 to 17 (Kavlock et al. 1981)
Test for Scaled residualsc

significant Dose Dose
difference Variance Means below above Overall BMDRD10 BMDL RD10
Model p-valuea p-valueb p-valueb BMD BMD largest AIC (mg/kg/day) (mg/kg/day)
Constant variance with high dose dropped (high dose animal data insufficient for modeling)
Lineard <0.0001 0.0122 0.3704 0.764 -1 -1 43.880 NA NA
Nonconstant variance with high dose dropped (high dose animal data insufficient for modeling)
Lineard <0.0001 0.0867 0.2503 -0.654 -1.21 -1.21 40.640 NA NA
Constant variance with two highest doses dropped
Lineard <0.0001 0.0046 0.356 0.745 -0.366 0.745 40.202 NA NA
Nonconstant variance with two highest doses dropped
Exponential <0.0001 0.4682 0.08941 -0.276 NA 0.752 33.996 NA NA
(model 2)e
Exponential <0.0001 0.4682 0.08941 -0.276 NA 0.752 33.996 NA NA
(model 3)e
Exponential <0.0001 0.4682 NA -0.3069 0.2135 -0.3069 33.111 NA NA
(model 4)e
Lineard <0.0001 0.4682 0.1003 -0.288 NA 0.73 33.812 1.06 NA
Polynomial <0.0001 0.4682 0.1003 -0.288 NA 0.73 33.812 1.06 0.69
(2-degree)d,f
Powere <0.0001 0.4682 0.1003 -0.288 NA 0.73 33.812 1.06 0.69
aValues >0.05 fail to meet conventional goodness-of-fit criteria.
bValues <0.10 fail to meet conventional goodness-of-fit criteria.
cScaled residuals at doses immediately below and above the benchmark dose; also the largest residual at any dose.
dCoefficients restricted to be positive.
ePower restricted to ≥1.
fSelected model. Nonconstant variance models provided adequate fit to the variance data with the two highest doses
dropped. With the nonconstant variance model applied, the linear, polynomial, and power models provide an
adequate fit. The three models appear to converge; however, BMDL computation failed for the linear model.
Therefore, the polynomial model was selected.
AIC = Akaike Information Criterion; BMD = maximum likelihood estimate of the exposure concentration associated
with the selected benchmark response; BMDL = 95% lower confidence limit on the BMD (subscripts denote
benchmark response: i.e., RD10 = exposure concentration associated with 10% relative deviation in outcome);
NA = not applicable (BMDL computation failed or model did not provide adequate fit to the data); RD = relative
deviation

ENDRIN A-15
APPENDIX A
Figure A-2. Fit of Polynomial (2-Degee) to Data for Maternal Relative Liver Weight
in Female Mice Following Gavage Administration of Endrin from GD 7 to 17
(Kavlock et al. 1981)
Polynomial Model, with BMR of 0.1 Rel. Dev. for the BMD and 0.95 Lower Confidence Limit for the BMDL
Polynomial
7.6
7.4
7.2
Mean Response
6.8
6.6
6.4
6.2 BMDL BMD
0 0.2 0.4 0.6 0.8 1

dose
15:23 03/30 2018

ENDRIN A-16
APPENDIX A

Date: May 2019
Route: Oral
Duration: Intermediate
MRL: 0.0006 mg/kg/day (adopt provisional acute oral MRL)
Critical Effect: Decreased locomotor activity
Reference: Kavlock et al. 1981
Point of Departure: BMDL1SD of 0.06 mg/kg/day
LSE Graph Key: 13
Species: Rat
MRL Summary: There are insufficient data for derivation of an intermediate-duration oral MRL.
Rationale for Not Deriving an MRL: An MRL was not derived for intermediate-duration oral exposure
because the MRL derived from the available data in the limited database would be higher than the
provisional acute-duration MRL. The provisional acute-duration MRL is expected to be protective of
intermediate-duration exposures; therefore, the provisional acute oral MRL is adopted as the provisional
intermediate oral MRL.
The intermediate-duration oral database for endrin is limited (see Table A-7). The lowest identified effect
level is for altered habituation in locomotor testing in PND 16 and 20 offspring following maternal
exposure to 0.15 mg/kg/day endrin via gavage from GD 7 to PND 15 (Gray et al. 1981). Young and
Mehendale (1986) reported hepatic LOAELs at slightly higher doses based on altered hepatic enzyme
levels or hepatobiliary function in rats exposed to endrin, endrin aldehyde, or endrin ketone at 0.25–
0.5 mg/kg/day for 15 days (Young and Mehendale 1986). The only other available studies reported
serious LOAELs for death in one dog exposed to endrin doses of 0.20–0.27 mg/kg/day for 47 days
(midpoint 0.24 mg/kg/day) (Treon et al. 1955) and mouse dams exposed to 0.65 mg/kg/day during
gestation (Good and Ware 1969).
Table A-7. Summary of Effects Following Intermediate Oral Exposure to Endrin
NOAEL LOAEL
Species Duration/route (mg/kg/day) (mg/kg/day) Effect Reference
Sublethal effects
CD rat 28 days 0.075a 0.15 Altered habituation in Gray et al. 1981
GD 7–PND 15 locomotor testing in
(GO) offspring on PND 16
and 20
Sprague-Dawley 15 days (F) ND 0.25 Altered hepatobiliary Young and
rat function (no change Mehendale
in serum chemistry; 1986
organ weight and
histology not
assessed)

ENDRIN A-17
APPENDIX A
Table A-7. Summary of Effects Following Intermediate Oral Exposure to Endrin
NOAEL LOAEL
Sprague-Dawley 15 days (F) ND 0.5 (endrin 10-fold increase in Young and
rat aldehyde) serum ALT and Mehendale
5-fold increase in 1986
serum AST (no
changes in
hepatobiliary
function; organ
weight and histology
not assessed)
Sprague-Dawley 15 days (F) ND 0.25 (endrin 8-fold increase in Young and
rat ketone) serum ALT (no Mehendale
changes in 1986
hepatobiliary
function; organ
weight and histology
not assessed)
Lethality
Beagle dog Up to NA 0.23 Death Treon et al.
9.9 months; 1955
6 days/week
(F)
Swiss mouse 120 days (F) NA 0.65 Maternal death Good and Ware
1969
aSelected POD.
ALT = alanine aminotransferase; AST = aspartate aminotransferase; F = feed; GD = gestation day; GO = gavage-oil;
LOAEL = lowest observed adverse effect level; MRL = minimal risk level; NA = not applicable; ND = not determined;
NOAEL = no-observed-adverse-effect level; PND = postnatal day; POD = point of departure
Altered locomotion in offspring from the Gray et al. (1981) study was selected as the critical effect
because it was the most sensitive effect observed in available studies. BMD modeling was conducted for
locomotor data from the final 15 minutes of the 45-minute locomotor trial, which showed the most
significant increases in locomotion compared with control (Table A-8). Values for modeling were
extracted from Figure 3B in the report using GrabIt! software. Using the BMD modeling approach
described in the acute-duration oral MRL worksheet, no adequate models were identified with either the
full dataset or the highest dose dropped. Therefore, the NOAEL of 0.075 mg/kg/day was selected as the
point-of-departure. Using a total uncertainty factor of 100 (10 for extrapolation from animals to humans
and 10 for human variability), the provisional intermediate-duration oral MRL would be
0.0008 mg/kg/day. This value is higher than the provisional acute-duration oral MRL of
0.0006 mg/kg/day based on a BMDL1SD of 0.06 mg/kg/day for decreased activity in adult female rats
(Kavlock et al. 1981). Therefore, there are no sufficient low-dose data to derive an intermediate-duration
oral MRL.

ENDRIN A-18
APPENDIX A
Table A-8. Locomotor Activity in PND 16–20 Rat Offspring Following Maternal
Exposure to Endrin from GD 7 to PND 15 via Gavage
Dose (mg/kg/day)
0 0.075 0.15 0.3
Locomotor activity (number of 43±8 39±6 71±10 83±13
photocell beam interruptions) (35) (34) (34) (8)
Mean±SDa (N)
aValues extracted from graphically presented data (Figure 3B) using GrabIt! Software.
GD = gestation day; N = number; PND = postnatal day; SD = standard deviation
Source: Gray et al. 1981

ENDRIN A-19
APPENDIX A

Date: May 2019
Route: Oral
Duration: Chronic
MRL 0.0003 mg/kg/day
Critical Effect: Hepatic lesions and occasional convulsions
Reference: Kettering 1969
Point of Departure: NOAEL of 0.025 mg/kg/day
LSE Graph Key: 52
Species: Dog
MRL Summary: A chronic oral MRL of 0.0003 mg/kg/day was derived for endrin based on convulsions
and hepatic lesions in dogs exposed to dietary endrin for 2 years (Kettering 1969). The MRL is based on
the NOAEL of 0.025 mg/kg/day for neurological and hepatic effects and a total uncertainty factor of
100 (10 for extrapolation from animals to humans and 10 for human variability).
Selection of the Critical Effect: The lowest LOAEL identified in the chronic oral database was
0.05 mg/kg/day in dogs exposed to dietary endrin for 2 years (Kettering 1969). Effects observed at this
dose included hepatic vacuolation in female dogs and occasional convulsions in one female dog; hepatic
and neurological effects were also observed in males at the next dose (0.1 mg/kg/day). Other reported
hepatic and neurological effects following chronic exposure to endrin are reviewed in Table A-9.
Observed effects in other systems occurred at doses ≥0.1 mg/kg.
While convulsions only occurred in one of six dogs at 0.05 mg/kg/day, neurological effects were
considered co-critical effects (along with hepatic effects) because the central nervous system is the
primary target system for endrin, as evidenced by reports of neurologic effects including convulsions and
tremors in humans and other animal species (Curley et al. 1970; Deichmann et al. 1970; Kettering 1969;
Treon et al. 1955; Waller et al. 1992).
Table A-9. Summary of Candidate Critical Effects for Chronic Oral MRL for
Endrin
NOAEL LOAEL
Beagle dog 2 years (F) 0.025a (females) 0.05 (females) Occasional Kettering 1969
0.05 (males) 0.10 (males) convulsions
(serious
LOAEL)
Beagle dog 64–156 weeks (F) ND 0.059 Seizures Kettering 1971
(serious
LOAEL)
Beagle dog 16.4–18.7 months 0.12 ND Treon et al.
6 days/week 1955
(F)

ENDRIN A-20
APPENDIX A
Table A-9. Summary of Candidate Critical Effects for Chronic Oral MRL for
Endrin
NOAEL LOAEL
Carworth rat 2 years (F) 0.25 1.25 Diffuse Treon et al.
(serious degeneration of 1955
LOAEL) the brain
Osborne- 17.6–20.8 months ND 0.1 Convulsions and Deichmann et
Mendel rat (F) (serious tremors al. 1970
LOAEL)
Osborne- 80 weeks (F) 0.3 ND NCI 1978
Mendel rat
B5C3F1 mouse 80 weeks (F) ND 0.21 M Hyperexcitability NCI 1978
0.33 F
Hepatic effects
Beagle dog 2 years (F) 0.025a (females) 0.05 (females) Hepatic cell Kettering 1969
0.05 (males) 0.10 (males) vacuolation
Beagle dog 64–156 weeks (F) 0.059 ND Kettering 1971
Carworth rat 2 years (F) 0.05 0.25 Increased liver Treon et al.
weight 1955
Osborne- 17.6–20.8 months ND 0.1 Cloudy swelling Deichmann et
Mendel rat (F) of centrilobular al. 1970
cells
Osborne- 80 weeks (F) 0.3 ND NCI 1978
Mendel rat
B6C3F1 mouse 80 weeks (F) 0.42 ND NCI 1978
aSelected POD.
F = feed; LOAEL = lowest observed adverse effect level; MRL = minimal risk level; ND = not determined;
NOAEL = no-observed-adverse-effect level; POD = point of departure
Selection of the Principal Study: The study with the lowest candidate POD (Kettering 1969) was
selected as the principal study.
Summary of the Principal Study:
Kettering Laboratory. 1969. Effects exerted upon beagle dogs during a period of two years by the
introduction of 1,2,3,4,10,10-hexachloro-6,7- epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4-endo, endo-
5,8-dimethanonaphthalene into their daily diets. Cincinnati, OH. Report to Velsicol Chemical
Corporation.
Groups of Beagle dogs (3/sex/group) were fed diets containing 0, 0.1, 0.5, 1.0, 2.0, or 4.0 ppm endrin for
2 years. Additional animals (4/sex/group) were included in the 0-, 1.0-, and 4.0-ppm groups for interim
sacrifice at 6 or 12 months (2/sex/group at each sacrifice). Using assumed food consumption of 0.32 kg
feed/day and body weights of 12.7 kg, estimated daily endrin intake levels were calculated to be 0.0025,
0.125, 0.025, 0.05, and 0.1 mg/kg/day for the 0.1, 0.5, 1.0, 2.0, and 4.0 ppm dose groups, respectively.
Dogs were observed daily for clinical signs of toxicity, and body weights were recorded weekly. Blood

ENDRIN A-21
APPENDIX A
was collected for hematological and clinical chemistry evaluation at 2 weeks and 1, 3, 6, 12, 18, and
24 months. Urine was collected for analysis at the same intervals. After 24 months, all females and two
males/group were sacrificed (the remaining male/group was retained for a special reproductive study,
results of this study not included in this report). The liver, heart, lungs, kidneys, spleen, brain, gonads,
pituitary, adrenals, and thyroids were weighed. The authors also microscopically examined these organs,
along with the gall bladder, aorta, stomach, duodenum-pylorus, small and large intestines, pancreas,
mesenteric lymph nodes, urinary bladder, prostate, uterus, thymus, spinal cord, eye, bone marrow, bone,
skeletal muscle, fat tissue, and skin.
The authors reported no deaths and no exposure-related changes in rate of growth, food consumption,
hematology, clinical chemistry, or urinalysis.
Convulsions (or physical evidence of having had a convulsion) were observed in one female and two
male dogs at 0.1 mg/kg/day and one female dog at 0.05 mg/kg/day. The study authors indicate that the
female from the 0.05 mg/kg/day group convulsed on two successive days after eating at 25 months (this is
unclear, since animals were scheduled for sacrifice after 24 months). At 0.1 mg/kg/day, one male showed
physical evidence of having had a convulsion after 5 months (not observed at any other time point), a
second male dog had several convulsions between 10 and 12 months of feeding (scheduled for interim
sacrifice at 12 months), and a female dog “probably” had a convulsion at 12 and 21 months and had
multiple observed convulsions at 23 months. Petechial hemorrhages and cerebral edema were observed
in the brain of one male dog having convulsions at the time of necropsy.
The study observed hepatic effects at the gross and microscopic levels. There were occasional slight
increases in the absolute weight of livers from dogs fed diets containing endrin at 0.05 and 0.1 mg/kg/day,
compared with control; however, average weights remained within 10% of control. Relative liver weights
at 0.05 and 0.1 mg/kg/day were decreased by 3 and 17% in males, respectively, and increased by 24 and
2% in females, respectively. No other potentially exposure-related organ weight changes were observed.
All dogs exposed to 0.1 mg/kg/day endrin showed moderate vacuolar degeneration in the hepatic cells
with diffuse brown pigment. One female exposed to 0.05 mg/kg/day also showed vacuolar degeneration
and pigmentation, and one male exposed to 0.05 showed brown pigmentation without vacuolar
degeneration. Concentrations of 0.05 and 0.1 mg/kg/day endrin were associated with slight to moderate
vacuolation of hepatic cells.
Based on hepatic and neurological effects, a NOAEL of 0.025 mg/kg/day and a LOAEL of
0.05 mg/kg/day were identified for this study.
Selection of the Point of Departure: The NOAEL of 0.025 mg/kg/day for neurological and hepatic
effects was selected as the POD.
Uncertainty Factor: The NOAEL is divided by a total uncertainty factor of 100:

• 10 for extrapolation from animals to humans
• 10 for human variability
MRL = NOAEL ÷ uncertainty factors

0.025 mg/kg/day ÷ (10x10) = 0.0003 mg/kg/day
Other Additional Studies or Pertinent Information: The central nervous system is the primary target
system for endrin as evidenced by reports of neurologic effects including convulsions and tremors in
humans acutely poisoned with endrin (Carbajal-Rodriquez et al. 1990; Coble et al. 1967; Curley et al.
1970; Davies and Lewis 1956; Rowley et al. 1987; Waller et al. 1992; Weeks 1967) and various animal

ENDRIN A-22
APPENDIX A
species following oral exposure (Chernoff et al. 1979a; Deichmann et al. 1970; Kavlock et al. 1981;
Kettering 1969; Mehrotra et al. 1989; Treon et al. 1955). Acute neurotoxic effects have also been
observed following high occupational exposure (Hoogendam et al. 1962, 1965). Limited animal evidence
also reports neurotoxicity following acute inhalation or dermal exposure (Gaines 1960; Pandy 1978;
Ressang et al. 1959; Treon et al. 1955).
The liver also appears to be a potential toxicity target of endrin. In laboratory animals, hepatic effects
been consistently reported following inhalation, oral, or dermal exposure at or near lethal levels in several
species, including increased liver weight, altered liver serum enzymes, diffuse degenerative lesions,
necrosis, vacuolation, fatty degeneration, and lipid peroxidation (Ali and Shakoori 1993; Bagchi et al.
1992a, 1992b, 1992c; Hassan et al. 1991; Hassoun et al. 1993; Kavlock et al. 1981; Lawrence et al. 1968,
Treon et al. 1955; Young and Mehendale 1986). In low-dose oral chronic studies, hepatic effects were
reported at sublethal effects in rats and dogs, including increased liver weight, cloudy swelling of
centrilobular cells, and vacuolation (Deichmann et al. 1970; Kettering 1969; Treon et al. 1955).

ENDRIN B-1
APPENDIX B. LITERATURE SEARCH FRAMEWORK FOR ENDRIN

The objective of the toxicological profile is to evaluate the potential for human exposure and the potential
health hazards associated with inhalation, oral, or dermal/ocular exposure to endrin.
B.1 LITERATURE SEARCH AND SCREEN
A literature search and screen was conducted to identify studies examining health effects, toxicokinetics,
mechanisms of action, susceptible populations, biomarkers, and chemical interactions data for endrin.
ATSDR primarily focused on peer-reviewed articles without publication date or language restrictions.
Non-peer-reviewed studies that were considered relevant to the assessment of the health effects of endrin
have undergone peer review by at least three ATSDR-selected experts who have been screened for
conflict of interest. The inclusion criteria used to identify relevant studies examining the health effects of
endrin are presented in Table B-1.
Table B-1. Inclusion Criteria for the Literature Search and Screen
Health Effects
Species
Human
Laboratory mammals
Route of exposure
Inhalation
Oral
Dermal (or ocular)
Parenteral (these studies will be considered supporting data)
Health outcome
Death
Systemic effects
Body weight effects
Respiratory effects
Cardiovascular effects
Gastrointestinal effects
Hematological effects
Musculoskeletal effects
Hepatic effects
Renal effects
Dermal effects
Ocular effects
Endocrine effects
Immunological effects
Reproductive effects
Developmental effects
Other noncancer effects
Cancer

ENDRIN B-2
APPENDIX B
Table B-1. Inclusion Criteria for the Literature Search and Screen
Toxicokinetics
Absorption
Distribution
Metabolism
Excretion
PBPK models
Biomarkers
Biomarkers of exposure
Biomarkers of effect
Interactions with other chemicals
B.1.1 Literature Search
The current literature search was intended to update the health effects sections of the existing
toxicological profile for endrin (ATSDR 1996), thus, the literature search was restricted to studies
published between January 1994 to April 2017. The following main databases were searched in April
2017:
• PubMed
• National Library of Medicine’s TOXLINE
• Scientific and Technical Information Network’s TOXCENTER
The search strategy used the chemical names, Chemical Abstracts Service (CAS) numbers,
synonyms, and Medical Subject Headings (MeSH) terms for endrin. The query strings used for the
literature search are presented in Table B-2.
The search was augmented by searching the Toxic Substances Control Act Test Submissions (TSCATS),
NTP website, and National Institute of Health Research Portfolio Online Reporting Tools Expenditures
and Results (NIH RePORTER) databases using the queries presented in Table B-3. Additional databases
were searched in the creation of various tables and figures, such as the TRI Explorer, the Substance
priority list (SPL) resource page, and other items as needed. Regulations applicable to endrin were
identified by searching international and U.S. agency websites and documents.
Review articles were identified and used for the purpose of providing background information and
identifying additional references. ATSDR also identified reports from the grey literature, which included
unpublished research reports, technical reports from government agencies, conference proceedings and
abstracts, and theses and dissertations.
Table B-2. Database Query Strings
Database
search date Query string
PubMed
04/2017 ((Endrin[MeSH] OR OB9NVE7YCL[rn] OR 7421-93-4[rn] OR 53494-70-5[rn]) AND
(1994/01/01 : 3000[dp] OR 1994/01/01 : 3000[mhda])) OR (("(1aalpha, 2beta, 2abeta,
3alpha, 6alpha, 6abeta, 7beta, 7aalpha)-3,4,5,6,9,9-hexachloro-1a, 2,2a, 3,6,6a, 7,7a-

ENDRIN B-3
APPENDIX B
Database
octahydro-2,7:3,6-dimethanonaphth(2,3-b)oxirene"[tw] OR "(1R, 4S, 4aS, 5S, 6S, 7R, 8R,
8aR)-1,2,3,4,10,10-Hexachloro-1,4,4a, 5,6,7,8,8a-octahydro-6,7-epoxy-1,4:5,8-
dimethanonaphthalene"[tw] OR "1,2,3,4,10,10-Hexachloro-1R, 4S, 4aS, 5S, 6,7R, 8R,
8aR-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene"[tw] OR "1,2,3,4,10,10-
Hexachloro-6,7-epoxy-1,4,4a, 5,6,7,8,8a-octahydro-endo, endo-1,4:5,8-
dimethanonaphthalene"[tw] OR "3,4,5,6,9,9-Hexachloro-1a, 2,2a, 3,6,6a, 7,7a-octahydro-
2,7:3,6-dimethanonaphth(2,3-b)oxirene"[tw] OR "3,4,5,6,9,9-Hexachloro-1aalpha, 2beta,
2abeta, 3alpha, 6alpha, 6abeta, 7beta, 7aalpha-octahydro-2,7:3,6-dimethanonaphth(2,3-
b)oxirene"[tw] OR "Compound 269"[tw] OR "EN 57"[tw] OR "Endrex"[tw] OR "Endricol"[tw]
OR "Endrin"[tw] OR "Endrin 20 EC"[tw] OR "Endrin isomer"[tw] OR "Endrine"[tw] OR
"Experimental insecticide 269"[tw] OR "Hexachloroepoxyoctahydro-endo, endo-
dimethanonaphthalene"[tw] OR "Hexadrin"[tw] OR "Latka 269"[tw] OR "Mendrin"[tw] OR
"Nendrin"[tw] OR "Oktanex"[tw] OR "OMS 197"[tw] OR "SD 3419"[tw] OR "Stardrin"[tw] OR
"Stardrin 20"[tw] OR "(1aR, 2R, 2aR, 3R, 6S, 6aS, 7S, 7aS)-rel-3,4,5,6,9,9-hexachloro-1a,
2,2a, 3,6,6a, 7,7a-octahydro-2,7:3,6-Dimethanonaphth(2,3-b)oxirene"[tw] OR "1,2,4-
Methenocyclopenta(cd)pentalene-5-carboxaldehyde, 2,2a, 3,3,4,7-hexachlorodecahydro-
,(1alpha, 2beta, 2abeta, 4beta, 4abeta, 5beta, 6abeta, 6bbeta, 7R*)-"[tw] OR "Endrin
aldehyde"[tw] OR "SD 7442"[tw] OR "delta-Keto 153"[tw] OR "delta-Ketoendrin"[tw] OR
"Endrin ketone"[tw] OR "SD 2614"[tw] OR "(2-alpha, 3a-beta, 3b-beta, 4-beta, 5-beta, 6a-
beta, 7-alpha, 7a-beta, 8R*)-3b, 4,5,6,6,6a-hexachlorodecahydro-2,5,7-Metheno-3H-
cyclopenta(a)pentalen-3-one"[tw] OR "(2R, 3aR, 3bS, 4R, 5R, 6aS, 7S, 7aR, 8R)-rel-3b,
4,5,6,6,6a-hexachlorodecahydro-2,5,7-Metheno-3H-cyclopenta(a)pentalen-3-one"[tw])
AND (1994/01/01 : 3000[dp] OR 1994/01/01 : 3000[crdat] OR 1994/01/01 : 3000[edat]))
Toxline
04/2017 ( " ( 1aalpha 2beta 2abeta 3alpha 6alpha 6abeta 7beta 7aalpha ) -3 4 5 6 9 9-hexachloro-
1a 2 2a 3 6 6a 7 7a-octahydro-2 7 3 6-dimethanonaphth ( 2 3-b ) oxirene" OR " ( 1r 4s 4as
5s 6s 7r 8r 8ar ) -1 2 3 4 10 10-hexachloro-1 4 4a 5 6 7 8 8a-octahydro-6 7-epoxy-1 4 5 8-
dimethanonaphthalene" OR "1 2 3 4 10 10-hexachloro-1r 4s 4as 5s 6 7r 8r 8ar-octahydro-
6 7-epoxy-1 4 5 8-dimethanonaphthalene" OR "1 2 3 4 10 10-hexachloro-6 7-epoxy-1 4 4a
5 6 7 8 8a-octahydro-endo endo-1 4 5 8-dimethanonaphthalene" OR "3 4 5 6 9 9-
hexachloro-1a 2 2a 3 6 6a 7 7a-octahydro-2 7 3 6-dimethanonaphth ( 2 3-b ) oxirene" OR
"3 4 5 6 9 9-hexachloro-1aalpha 2beta 2abeta 3alpha 6alpha 6abeta 7beta 7aalpha-
octahydro-2 7 3 6-dimethanonaphth ( 2 3-b ) oxirene" OR "compound 269" OR "en 57" OR
"endrex" OR "endricol" OR "endrin" OR "endrin 20 ec" OR "endrin isomer" OR "endrine"
OR "experimental insecticide 269" OR "hexachloroepoxyoctahydro-endo endo-
dimethanonaphthalene" OR "hexadrin" OR "latka 269" OR "mendrin" OR "nendrin" OR
"oktanex" OR "oms 197" OR "sd 3419" OR "stardrin" OR "stardrin 20" OR " ( 1ar 2r 2ar 3r
6s 6as 7s 7as ) -rel-3 4 5 6 9 9-hexachloro-1a 2 2a 3 6 6a 7 7a-octahydro-2 7 3 6-
dimethanonaphth ( 2 3-b ) oxirene" OR "1 2 4-methenocyclopenta ( cd ) pentalene-5-
carboxaldehyde 2 2a 3 3 4 7-hexachlorodecahydro- ( 1alpha 2beta 2abeta 4beta 4abeta
5beta 6abeta 6bbeta 7r* ) -" OR "endrin aldehyde" OR "sd 7442" OR "delta-keto 153" OR
"delta-ketoendrin" OR "endrin ketone" OR "sd 2614" OR " ( 2-alpha 3a-beta 3b-beta 4-beta
5-beta 6a-beta 7-alpha 7a-beta 8r* ) -3b 4 5 6 6 6a-hexachlorodecahydro-2 5 7-metheno-
3h-cyclopenta ( a ) pentalen-3-one" OR " ( 2r 3ar 3bs 4r 5r 6as 7s 7ar 8r ) -rel-3b 4 5 6 6
6a-hexachlorodecahydro-2 5 7-metheno-3h-cyclopenta ( a ) pentalen-3-one" OR 72-20-8
[rn] OR 7421-93-4 [rn] OR 53494-70-5 [rn] ) AND 1994:2017 [yr] AND ( ANEUPL [org] OR
BIOSIS [org] OR CIS [org] OR DART [org] OR EMIC [org] OR EPIDEM [org] OR HEEP
[org] OR HMTC [org] OR IPA [org] OR RISKLINE [org] OR MTGABS [org] OR NIOSH [org]
OR NTIS [org] OR PESTAB [org] OR PPBIB [org] ) AND NOT PubMed [org] AND NOT
pubdart [org]

ENDRIN B-4
APPENDIX B
Database
Toxcenter
04/2017 (FILE 'HOME' ENTERED AT 10:22:22 ON 04 APR 2017)
FILE 'TOXCENTER' ENTERED AT 10:22:39 ON 04 APR 2017

CHARGED TO COST=EH011.13.01.01
L1 7361 SEA 72-20-8 OR 7421-93-4 OR 53494-70-5
L2 7329 SEA L1 NOT TSCATS/FS
L3 7203 SEA L2 NOT PATENT/DT
L4 3243 SEA L3 AND PY>=1994
ACTIVATE TOXQUERY/Q
---------
L5 QUE (CHRONIC OR IMMUNOTOX? OR NEUROTOX? OR TOXICOKIN? OR
BIOMARKER? OR NEUROLOG?)
L6 QUE (PHARMACOKIN? OR SUBCHRONIC OR PBPK OR
EPIDEMIOLOGY/ST,CT,
IT)
L7 QUE (ACUTE OR SUBACUTE OR LD50# OR LD(W)50 OR LC50# OR
LC(W)50)
L8 QUE (TOXICITY OR ADVERSE OR POISONING)/ST,CT,IT
L9 QUE (INHAL? OR PULMON? OR NASAL? OR LUNG? OR RESPIR?)
L10 QUE ((OCCUPATION? OR WORKPLACE? OR WORKER?) AND EXPOS?)
L11 QUE (ORAL OR ORALLY OR INGEST? OR GAVAGE? OR DIET OR DIETS
OR
DIETARY OR DRINKING(W)WATER?)
L12 QUE (MAXIMUM AND CONCENTRATION? AND (ALLOWABLE OR
PERMISSIBLE))
L13 QUE (ABORT? OR ABNORMALIT? OR EMBRYO? OR CLEFT? OR FETUS?)

L14 QUE (FOETUS? OR FETAL? OR FOETAL? OR FERTIL? OR MALFORM?
OR
OVUM?)
L15 QUE (OVA OR OVARY OR PLACENTA? OR PREGNAN? OR PRENATAL?)
L16 QUE (PERINATAL? OR POSTNATAL? OR REPRODUC? OR STERIL? OR
TERATOGEN?)
L17 QUE (SPERM OR SPERMAC? OR SPERMAG? OR SPERMATI? OR
SPERMAS? OR
SPERMATOB? OR SPERMATOC? OR SPERMATOG?)
L18 QUE (SPERMATOI? OR SPERMATOL? OR SPERMATOR? OR
SPERMATOX? OR
SPERMATOZ? OR SPERMATU? OR SPERMI? OR SPERMO?)
L19 QUE (NEONAT? OR NEWBORN? OR DEVELOPMENT OR
DEVELOPMENTAL?)
L20 QUE (ENDOCRIN? AND DISRUPT?)
L21 QUE (ZYGOTE? OR CHILD OR CHILDREN OR ADOLESCEN? OR
INFANT?)
L22 QUE (WEAN? OR OFFSPRING OR AGE(W)FACTOR?)
L23 QUE (DERMAL? OR DERMIS OR SKIN OR EPIDERM? OR CUTANEOUS?)
L24 QUE (CARCINOG? OR COCARCINOG? OR CANCER? OR PRECANCER?
OR
NEOPLAS?)

ENDRIN B-5
APPENDIX B
Database
L25 QUE (TUMOR? OR TUMOUR? OR ONCOGEN? OR LYMPHOMA? OR
CARCINOM?)
L26 QUE (GENETOX? OR GENOTOX? OR MUTAGEN? OR
GENETIC(W)TOXIC?)
L27 QUE (NEPHROTOX? OR HEPATOTOX?)
L28 QUE (ENDOCRIN? OR ESTROGEN? OR ANDROGEN? OR HORMON?)
L29 QUE (OCCUPATION? OR WORKER? OR WORKPLACE? OR EPIDEM?)
L30 QUE L5 OR L6 OR L7 OR L8 OR L9 OR L10 OR L11 OR L12 OR L13 OR
L14 OR L15 OR L16 OR L17 OR L18 OR L19 OR L20 OR L21 OR L22 OR
L23 OR L24 OR L25 OR L26 OR L27 OR L28 OR L29
L31 QUE (RAT OR RATS OR MOUSE OR MICE OR GUINEA(W)PIG? OR
MURIDAE
OR DOG OR DOGS OR RABBIT? OR HAMSTER? OR PIG OR PIGS OR
SWINE
OR PORCINE OR MONKEY? OR MACAQUE?)
L32 QUE (MARMOSET? OR FERRET? OR GERBIL? OR RODENT? OR
LAGOMORPHA
OR BABOON? OR CANINE OR CAT OR CATS OR FELINE OR MURINE)
L33 QUE L30 OR L31 OR L32
L34 QUE (NONHUMAN MAMMALS)/ORGN
L35 QUE L33 OR L34
L36 QUE (HUMAN OR HUMANS OR HOMINIDAE OR MAMMALS OR MAMMAL?
OR
PRIMATES OR PRIMATE?)
L37 QUE L35 OR L36
---------
L38 1399 SEA L4 AND L37
L39 21 SEA L38 AND MEDLINE/FS
L40 179 SEA L38 AND BIOSIS/FS
L41 1180 SEA L38 AND CAPLUS/FS
L42 19 SEA L38 NOT (MEDLINE/FS OR BIOSIS/FS OR CAPLUS/FS)
L43 1281 DUP REM L39 L40 L42 L41 (118 DUPLICATES REMOVED)
L44 145 SEA L40 AND PY>1998
L45 1015 SEA L41 NOT DEVELOPMENT
L*** DEL 21 S L38 AND MEDLINE/FS
L46 21 SEA L43
L*** DEL 179 S L38 AND BIOSIS/FS
L47 166 SEA L43
L*** DEL 1180 S L38 AND CAPLUS/FS
L48 1081 SEA L43
L*** DEL 19 S L38 NOT (MEDLINE/FS OR BIOSIS/FS OR CAPLUS/FS)
L49 13 SEA L43
L50 166 SEA (L46 OR L47 OR L48 OR L49) AND BIOSIS/FS
L51 21 SEA L43

ENDRIN B-6
APPENDIX B
Database
L52 166 SEA L43
L53 1081 SEA L43
L54 13 SEA L43
L55 1081 SEA (L51 OR L52 OR L53 OR L54) AND CAPLUS/FS
L56 21 SEA L43
L57 166 SEA L43
L58 1081 SEA L43
L59 13 SEA L43
L60 13 SEA (L56 OR L57 OR L58 OR L59) NOT (MEDLINE/FS OR BIOSIS/FS OR
CAPLUS/FS)
L61 5 SEA L55 AND ENDRIN/TI
L62 179 SEA L50 OR L60
L63 21 SEA L43
L64 166 SEA L43
L65 1081 SEA L43
L66 13 SEA L43
L67 1260 SEA (L63 OR L64 OR L65 OR L66) NOT MEDLINE/FS
D SCAN L67
Table B-3. Strategies to Augment the Literature Search
Source Query and number screened when available

TSCATSa
04/2017 Compounds searched: 72-20-8; 7421-93-4; 53494-70-5
NTP
04/2017 72-20-8

ENDRIN B-7
APPENDIX B
Table B-3. Strategies to Augment the Literature Search
Source Query and number screened when available

Endrin
7421-93-4
Endrin aldehyde
53494-70-5
delta-Keto 153
Endrin ketone
NIH RePORTER
11/2017 Text Search: "72-20-8" OR "7421-93-4" OR "53494-70-5" OR "(1aalpha, 2beta,
2abeta, 3alpha, 6alpha, 6abeta, 7beta, 7aalpha)-3,4,5,6,9,9-hexachloro-1a, 2,2a,
3,6,6a, 7,7a-octahydro-2,7:3,6-dimethanonaphth(2,3-b)oxirene" OR "(1R, 4S, 4aS, 5S,
6S, 7R, 8R, 8aR)-1,2,3,4,10,10-Hexachloro-1,4,4a, 5,6,7,8,8a-octahydro-6,7-epoxy-
1,4:5,8-dimethanonaphthalene" OR "1,2,3,4,10,10-Hexachloro-1R, 4S, 4aS, 5S, 6,7R,
8R, 8aR-octahydro-6,7-epoxy-1,4:5,8-dimethanonaphthalene" OR "1,2,3,4,10,10-
Hexachloro-6,7-epoxy-1,4,4a, 5,6,7,8,8a-octahydro-endo, endo-1,4:5,8-
dimethanonaphthalene" OR "3,4,5,6,9,9-Hexachloro-1a, 2,2a, 3,6,6a, 7,7a-octahydro-
2,7:3,6-dimethanonaphth(2,3-b)oxirene" OR "3,4,5,6,9,9-Hexachloro-1aalpha, 2beta,
2abeta, 3alpha, 6alpha, 6abeta, 7beta, 7aalpha-octahydro-2,7:3,6-
dimethanonaphth(2,3-b)oxirene" OR "Compound 269" OR "EN 57" OR "Endrex" OR
"Endricol" OR "Endrin" OR "Endrin 20 EC" OR "Endrin isomer" OR "Endrine" OR
"Experimental insecticide 269" OR "Hexachloroepoxyoctahydro-endo, endo-
dimethanonaphthalene" OR "Hexadrin" OR "Latka 269" OR "Mendrin" OR "Nendrin"
OR "Oktanex" OR "OMS 197" OR "SD 3419" OR "Stardrin" OR "Stardrin 20" OR
"(1aR, 2R, 2aR, 3R, 6S, 6aS, 7S, 7aS)-rel-3,4,5,6,9,9-hexachloro-1a, 2,2a, 3,6,6a,
7,7a-octahydro-2,7:3,6-Dimethanonaphth(2,3-b)oxirene" OR "1,2,4-
Methenocyclopenta(cd)pentalene-5-carboxaldehyde, 2,2a, 3,3,4,7-
hexachlorodecahydro-,(1alpha, 2beta, 2abeta, 4beta, 4abeta, 5beta, 6abeta, 6bbeta,
7R)-" OR "Endrin aldehyde" OR "SD 7442" OR "delta-Keto 153" OR "delta-Ketoendrin"
OR "Endrin ketone" OR "SD 2614" OR "(2-alpha, 3a-beta, 3b-beta, 4-beta, 5-beta, 6a-
beta, 7-alpha, 7a-beta, 8R)-3b, 4,5,6,6,6a-hexachlorodecahydro-2,5,7-Metheno-3H-
cyclopenta(a)pentalen-3-one" OR "(2R, 3aR, 3bS, 4R, 5R, 6aS, 7S, 7aR, 8R)-rel-3b,
4,5,6,6,6a-hexachlorodecahydro-2,5,7-Metheno-3H-cyclopenta(a)pentalen-3-one"
(Advanced), Search in: Projects Admin IC: All, Fiscal Year: Active Projects
Text Search: Endrin OR Hexadrin OR dimethanonaphth OR hexachlorodecahydro OR

"Hexachloroepoxyoctahydro-endo, endo-dimethanonaphthalene" (Advanced), Search
in: Projects Admin IC:All, Fiscal Year: Active Projects
Other Identified throughout the assessment process
aSeveral versions of the TSCATS database were searched, as needed, by CASRN including TSCATS1 via Toxline
(no date limit), TSCATS2 via https://yosemite.epa.gov/oppts/epatscat8.nsf/ReportSearch?OpenForm (date restricted
by EPA receipt date), and TSCATS via CDAT (date restricted by ‘Mail Received Date Range’), as well as google for
recent TSCA submissions.
The 2017 results were:

• Number of records identified from PubMed, TOXLINE, and TOXCENTER (after duplicate
removal): 1,961
• Number of records identified from other strategies: 42
• Total number of records to undergo literature screening: 2,003

ENDRIN B-8
APPENDIX B
B.1.2 Literature Screening
A two-step process was used to screen the literature search to identify relevant studies on endrin:
• Title and abstract screen

• Full text screen
Title and Abstract Screen. Within the reference library, titles and abstracts were screened manually for
relevance. Studies that were considered relevant (see Table B-1 for inclusion criteria) were moved to the
second step of the literature screening process. Studies were excluded when the title and abstract clearly
indicated that the study was not relevant to the toxicological profile.
• Number of titles and abstracts screened: 2,003

• Number of studies considered relevant and moved to the next step: 123
Full Text Screen. The second step in the literature screening process was a full text review of individual
studies considered relevant in the title and abstract screen step. Each study was reviewed to determine
whether it was relevant for inclusion in the toxicological profile.
• Number of studies undergoing full text review: 123

• Number of studies cited in the health effects sections of the existing toxicological profile
(August,1996): 92
• Total number of studies cited in the health effects sections of the updated profile: 149 (57 new
studies)
A summary of the results of the literature search and screening is presented in Figure B-1.

ENDRIN B-9
APPENDIX B
Figure B-1. March 2017 Literature Search Results and Screen for Endrin

ENDRIN C-1
APPENDIX C. USER'S GUIDE

Chapter 1. Relevance to Public Health
This chapter provides an overview of U.S. exposures, a summary of health effects based on evaluations of
existing toxicologic, epidemiologic, and toxicokinetic information, and an overview of the minimal risk
levels. This is designed to present interpretive, weight-of-evidence discussions for human health
endpoints by addressing the following questions:
1. What effects are known to occur in humans?
2. What effects observed in animals are likely to be of concern to humans?
3. What exposure conditions are likely to be of concern to humans, especially around hazardous
waste sites?
Minimal Risk Levels (MRLs)
Where sufficient toxicologic information is available, ATSDR derives MRLs for inhalation and oral
routes of entry at each duration of exposure (acute, intermediate, and chronic). These MRLs are not
meant to support regulatory action, but to acquaint health professionals with exposure levels at which
adverse health effects are not expected to occur in humans.
MRLs should help physicians and public health officials determine the safety of a community living near
a hazardous substance emission, given the concentration of a contaminant in air or the estimated daily
dose in water. MRLs are based largely on toxicological studies in animals and on reports of human
occupational exposure.
MRL users should be familiar with the toxicologic information on which the number is based.
Section 1.2, Summary of Health Effects, contains basic information known about the substance. Other
sections, such as Section 3.2 Children and Other Populations that are Unusually Susceptible and
Section 3.4 Interactions with Other Substances, provide important supplemental information.
MRL users should also understand the MRL derivation methodology. MRLs are derived using a
modified version of the risk assessment methodology that the Environmental Protection Agency (EPA)
provides (Barnes and Dourson 1988) to determine reference doses (RfDs) for lifetime exposure.
To derive an MRL, ATSDR generally selects the most sensitive endpoint which, in its best judgement,
represents the most sensitive human health effect for a given exposure route and duration. ATSDR
cannot make this judgement or derive an MRL unless information (quantitative or qualitative) is available
for all potential systemic, neurological, and developmental effects. If this information and reliable
quantitative data on the chosen endpoint are available, ATSDR derives an MRL using the most sensitive
species (when information from multiple species is available) with the highest no-observed-adverse-effect
level (NOAEL) that does not exceed any adverse effect levels. When a NOAEL is not available, a
lowest-observed-adverse-effect level (LOAEL) can be used to derive an MRL, and an uncertainty factor
of 10 must be employed. Additional uncertainty factors of 10 must be used both for human variability to
protect sensitive subpopulations (people who are most susceptible to the health effects caused by the
substance) and for interspecies variability (extrapolation from animals to humans). In deriving an MRL,
these individual uncertainty factors are multiplied together. The product is then divided into the
inhalation concentration or oral dosage selected from the study. Uncertainty factors used in developing a

ENDRIN C-2
APPENDIX C
substance-specific MRL are provided in the footnotes of the levels of significant exposure (LSE) tables
that are provided in Chapter 2. Detailed discussions of the MRLs are presented in Appendix A.
Chapter 2. Health Effects
Tables and Figures for Levels of Significant Exposure (LSE)
Tables and figures are used to summarize health effects and illustrate graphically levels of exposure
associated with those effects. These levels cover health effects observed at increasing dose
concentrations and durations, differences in response by species and MRLs to humans for noncancer
endpoints. The LSE tables and figures can be used for a quick review of the health effects and to locate
data for a specific exposure scenario. The LSE tables and figures should always be used in conjunction
with the text. All entries in these tables and figures represent studies that provide reliable, quantitative
estimates of NOAELs, LOAELs, or Cancer Effect Levels (CELs).
The legends presented below demonstrate the application of these tables and figures. Representative
examples of LSE tables and figures follow. The numbers in the left column of the legends correspond to
the numbers in the example table and figure.
TABLE LEGEND
See Sample LSE Table (page C-5)
(1) Route of exposure. One of the first considerations when reviewing the toxicity of a substance
using these tables and figures should be the relevant and appropriate route of exposure.
Typically, when sufficient data exist, three LSE tables and two LSE figures are presented in the
document. The three LSE tables present data on the three principal routes of exposure
(i.e., inhalation, oral, and dermal). LSE figures are limited to the inhalation and oral routes. Not
all substances will have data on each route of exposure and will not, therefore, have all five of the
tables and figures. Profiles with more than one chemical may have more LSE tables and figures.
(2) Exposure period. Three exposure periods—acute (<15 days), intermediate (15–364 days), and
chronic (≥365 days)—are presented within each relevant route of exposure. In this example, two
oral studies of chronic-duration exposure are reported. For quick reference to health effects
occurring from a known length of exposure, locate the applicable exposure period within the LSE
table and figure.
(3) Figure key. Each key number in the LSE table links study information to one or more data points
using the same key number in the corresponding LSE figure. In this example, the study
represented by key number 51 identified NOAELs and less serious LOAELs (also see the three
"51R" data points in sample LSE Figure 2-X).
(4) Species (strain) No./group. The test species (and strain), whether animal or human, are identified
in this column. The column also contains information on the number of subjects and sex per
group. Chapter 1, Relevance to Public Health, covers the relevance of animal data to human
toxicity and Section 3.1, Toxicokinetics, contains any available information on comparative
toxicokinetics. Although NOAELs and LOAELs are species specific, the levels are extrapolated
to equivalent human doses to derive an MRL.
(5) Exposure parameters/doses. The duration of the study and exposure regimens are provided in
these columns. This permits comparison of NOAELs and LOAELs from different studies. In
this case (key number 51), rats were orally exposed to “Chemical X” via feed for 2 years. For a

ENDRIN C-3
APPENDIX C
more complete review of the dosing regimen, refer to the appropriate sections of the text or the
original reference paper (i.e., Aida et al. 1992).
(6) Parameters monitored. This column lists the parameters used to assess health effects. Parameters
monitored could include serum (blood) chemistry (BC), behavioral (BH), biochemical changes
(BI), body weight (BW), clinical signs (CS), developmental toxicity (DX), enzyme activity (EA),
food intake (FI), fetal toxicity (FX), gross necropsy (GN), hematology (HE), histopathology
(HP), lethality (LE), maternal toxicity (MX), organ function (OF), ophthalmology (OP), organ
weight (OW), teratogenicity (TG), urinalysis (UR), and water intake (WI).
(7) Endpoint. This column lists the endpoint examined. The major categories of health endpoints
included in LSE tables and figures are death, body weight, respiratory, cardiovascular,
gastrointestinal, hematological, musculoskeletal, hepatic, renal, dermal, ocular, endocrine,
immunological, neurological, reproductive, developmental, other noncancer, and cancer. "Other
noncancer" refers to any effect (e.g., alterations in blood glucose levels) not covered in these
systems. In the example of key number 51, three endpoints (body weight, hematological, and
hepatic) were investigated.
(8) NOAEL. A NOAEL is the highest exposure level at which no adverse effects were seen in the
organ system studied. The body weight effect reported in key number 51 is a NOAEL at
25.5 mg/kg/day. NOAELs are not reported for cancer and death; with the exception of these two
endpoints, this field is left blank if no NOAEL was identified in the study.
(9) LOAEL. A LOAEL is the lowest dose used in the study that caused an adverse health effect.
LOAELs have been classified into "Less Serious" and "Serious" effects. These distinctions help
readers identify the levels of exposure at which adverse health effects first appear and the
gradation of effects with increasing dose. A brief description of the specific endpoint used to
quantify the adverse effect accompanies the LOAEL. Key number 51 reports a less serious
LOAEL of 6.1 mg/kg/day for the hepatic system, which was used to derive a chronic exposure,
oral MRL of 0.008 mg/kg/day (see footnote "c"). MRLs are not derived from serious LOAELs.
A cancer effect level (CEL) is the lowest exposure level associated with the onset of
carcinogenesis in experimental or epidemiologic studies. CELs are always considered serious
effects. The LSE tables and figures do not contain NOAELs for cancer, but the text may report
doses not causing measurable cancer increases. If no LOAEL/CEL values were identified in the
study, this field is left blank.
(10) Reference. The complete reference citation is provided in Chapter 8 of the profile.
(11) Footnotes. Explanations of abbreviations or reference notes for data in the LSE tables are found
in the footnotes. For example, footnote "c" indicates that the LOAEL of 6.1 mg/kg/day in key
number 51 was used to derive an oral MRL of 0.008 mg/kg/day.
FIGURE LEGEND
See Sample LSE Figure (page C-6)
LSE figures graphically illustrate the data presented in the corresponding LSE tables. Figures help the
reader quickly compare health effects according to exposure concentrations for particular exposure
periods.
(13) Exposure period. The same exposure periods appear as in the LSE table. In this example, health
effects observed within the chronic exposure period are illustrated.

ENDRIN C-4
APPENDIX C
(14) Endpoint. These are the categories of health effects for which reliable quantitative data exist.
The same health effect endpoints appear in the LSE table.
(15) Levels of exposure. Concentrations or doses for each health effect in the LSE tables are
graphically displayed in the LSE figures. Exposure concentration or dose is measured on the log
scale "y" axis. Inhalation exposure is reported in mg/m3 or ppm and oral exposure is reported in
mg/kg/day.
(16) LOAEL. In this example, the half-shaded circle that is designated 51R identifies a LOAEL
critical endpoint in the rat upon which a chronic oral exposure MRL is based. The key number
51 corresponds to the entry in the LSE table. The dashed descending arrow indicates the
extrapolation from the exposure level of 6.1 mg/kg/day (see entry 51 in the sample LSE table) to
the MRL of 0.008 mg/kg/day (see footnote "c" in the sample LSE table).
(17) CEL. Key number 59R is one of studies for which CELs were derived. The diamond symbol
refers to a CEL for the test species (rat). The number 59 corresponds to the entry in the LSE
table.
(18) Key to LSE figure. The key provides the abbreviations and symbols used in the figure.

ENDRIN C-5
APPENDIX C

ENDRIN C-6
APPENDIX C

ENDRIN D-1
APPENDIX D. QUICK REFERENCE FOR HEALTH CARE PROVIDERS
Toxicological Profiles are a unique compilation of toxicological information on a given hazardous

substance. Each profile reflects a comprehensive and extensive evaluation, summary, and interpretation
of available toxicologic and epidemiologic information on a substance. Health care providers treating
patients potentially exposed to hazardous substances may find the following information helpful for fast
answers to often-asked questions.
Primary Chapters/Sections of Interest
Chapter 1: Relevance to Public Health: The Relevance to Public Health Section provides an overview
of exposure and health effects and evaluates, interprets, and assesses the significance of toxicity
data to human health. A table listing minimal risk levels (MRLs) is also included in this chapter.
Chapter 2: Health Effects: Specific health effects identified in both human and animal studies are
reported by type of health effect (e.g., death, hepatic, renal, immune, reproductive), route of
exposure (e.g., inhalation, oral, dermal), and length of exposure (e.g., acute, intermediate, and
chronic).
NOTE: Not all health effects reported in this section are necessarily observed in the clinical
setting.
Pediatrics:
Section 3.2 Children and Other Populations that are Unusually Susceptible
Section 3.3 Biomarkers of Exposure and Effect
ATSDR Information Center
Phone: 1-800-CDC-INFO (800-232-4636) or 1-888-232-6348 (TTY)

Internet: http://www.atsdr.cdc.gov
The following additional materials are available online:
Case Studies in Environmental Medicine are self-instructional publications designed to increase primary
health care providers’ knowledge of a hazardous substance in the environment and to aid in the
evaluation of potentially exposed patients (see https://www.atsdr.cdc.gov/csem/csem.html).
Managing Hazardous Materials Incidents is a three-volume set of recommendations for on-scene

(prehospital) and hospital medical management of patients exposed during a hazardous materials
incident (see https://www.atsdr.cdc.gov/MHMI/index.asp). Volumes I and II are planning guides
to assist first responders and hospital emergency department personnel in planning for incidents
that involve hazardous materials. Volume III—Medical Management Guidelines for Acute
Chemical Exposures—is a guide for health care professionals treating patients exposed to
hazardous materials.
Fact Sheets (ToxFAQs™) provide answers to frequently asked questions about toxic substances (see
https://www.atsdr.cdc.gov/toxfaqs/Index.asp).

ENDRIN D-2
APPENDIX D
Other Agencies and Organizations
The National Center for Environmental Health (NCEH) focuses on preventing or controlling disease,
injury, and disability related to the interactions between people and their environment outside the
workplace. Contact: NCEH, Mailstop F-29, 4770 Buford Highway, NE, Atlanta, GA
30341-3724 • Phone: 770-488-7000 • FAX: 770-488-7015 • Web Page:
https://www.cdc.gov/nceh/.
The National Institute for Occupational Safety and Health (NIOSH) conducts research on occupational
diseases and injuries, responds to requests for assistance by investigating problems of health and
safety in the workplace, recommends standards to the Occupational Safety and Health
Administration (OSHA) and the Mine Safety and Health Administration (MSHA), and trains
professionals in occupational safety and health. Contact: NIOSH, 395 E Street, S.W., Suite 9200,
Patriots Plaza Building, Washington, DC 20201 • Phone: 202-245-0625 or 1-800-CDC-INFO
(800-232-4636) • Web Page: https://www.cdc.gov/niosh/.
The National Institute of Environmental Health Sciences (NIEHS) is the principal federal agency for
biomedical research on the effects of chemical, physical, and biologic environmental agents on
human health and well-being. Contact: NIEHS, PO Box 12233, 104 T.W. Alexander Drive,
Research Triangle Park, NC 27709 • Phone: 919-541-3212 • Web Page:
https://www.niehs.nih.gov/.
Clinical Resources (Publicly Available Information)
The Association of Occupational and Environmental Clinics (AOEC) has developed a network of clinics
in the United States to provide expertise in occupational and environmental issues. Contact:
AOEC, 1010 Vermont Avenue, NW, #513, Washington, DC 20005 • Phone: 202-347-4976
• FAX: 202-347-4950 • e-mail: AOEC@AOEC.ORG • Web Page: http://www.aoec.org/.
The American College of Occupational and Environmental Medicine (ACOEM) is an association of

physicians and other health care providers specializing in the field of occupational and
environmental medicine. Contact: ACOEM, 25 Northwest Point Boulevard, Suite 700, Elk
Grove Village, IL 60007-1030 • Phone: 847-818-1800 • FAX: 847-818-9266 • Web Page:
http://www.acoem.org/.
The American College of Medical Toxicology (ACMT) is a nonprofit association of physicians with
recognized expertise in medical toxicology. Contact: ACMT, 10645 North Tatum Boulevard,
Suite 200-111, Phoenix AZ 85028 • Phone: 844-226-8333 • FAX: 844-226-8333 • Web Page:
http://www.acmt.net.
The Pediatric Environmental Health Specialty Units (PEHSUs) is an interconnected system of specialists
who respond to questions from public health professionals, clinicians, policy makers, and the
public about the impact of environmental factors on the health of children and reproductive-aged
adults. Contact information for regional centers can be found at http://pehsu.net/findhelp.html.
The American Association of Poison Control Centers (AAPCC) provide support on the prevention and
treatment of poison exposures. Contact: AAPCC, 515 King Street, Suite 510, Alexandria VA
22314 • Phone: 701-894-1858 • Poison Help Line: 1-800-222-1222 • Web Page:
http://www.aapcc.org/.

ENDRIN E-1
APPENDIX E. GLOSSARY
Absorption—The process by which a substance crosses biological membranes and enters systemic
circulation. Absorption can also refer to the taking up of liquids by solids, or of gases by solids or liquids.
Acute Exposure—Exposure to a chemical for a duration of ≤14 days, as specified in the Toxicological
Profiles.
Adsorption—The adhesion in an extremely thin layer of molecules (as of gases, solutes, or liquids) to the
surfaces of solid bodies or liquids with which they are in contact.
Adsorption Coefficient (Koc)—The ratio of the amount of a chemical adsorbed per unit weight of
organic carbon in the soil or sediment to the concentration of the chemical in solution at equilibrium.
Adsorption Ratio (Kd)—The amount of a chemical adsorbed by sediment or soil (i.e., the solid phase)
divided by the amount of chemical in the solution phase, which is in equilibrium with the solid phase, at a
fixed solid/solution ratio. It is generally expressed in micrograms of chemical sorbed per gram of soil or
sediment.
Benchmark Dose (BMD) or Benchmark Concentration (BMC)—is the dose/concentration

corresponding to a specific response level estimate using a statistical dose-response model applied to
either experimental toxicology or epidemiology data. For example, a BMD10 would be the dose
corresponding to a 10% benchmark response (BMR). The BMD is determined by modeling the dose-
response curve in the region of the dose-response relationship where biologically observable data are
feasible. The BMDL or BMCL is the 95% lower confidence limit on the BMD or BMC.
Bioconcentration Factor (BCF)—The quotient of the concentration of a chemical in aquatic organisms

at a specific time or during a discrete time period of exposure divided by the concentration in the
surrounding water at the same time or during the same period.
Biomarkers—Indicators signaling events in biologic systems or samples, typically classified as markers

of exposure, effect, and susceptibility.
Cancer Effect Level (CEL)—The lowest dose of a chemical in a study, or group of studies, that
produces significant increases in the incidence of cancer (or tumors) between the exposed population and
its appropriate control.
Carcinogen—A chemical capable of inducing cancer.
Case-Control Study—A type of epidemiological study that examines the relationship between a
particular outcome (disease or condition) and a variety of potential causative agents (such as toxic
chemicals). In a case-control study, a group of people with a specified and well-defined outcome is
identified and compared to a similar group of people without the outcome.
Case Report—A report that describes a single individual with a particular disease or exposure. These
reports may suggest some potential topics for scientific research, but are not actual research studies.
Case Series—Reports that describe the experience of a small number of individuals with the same
disease or exposure. These reports may suggest potential topics for scientific research, but are not actual
research studies.

ENDRIN E-2
APPENDIX E
Ceiling Value—A concentration that must not be exceeded.
Chronic Exposure—Exposure to a chemical for ≥365 days, as specified in the Toxicological Profiles.
Clastogen—A substance that causes breaks in chromosomes resulting in addition, deletion, or

rearrangement of parts of the chromosome.
Cohort Study—A type of epidemiological study of a specific group or groups of people who have had a
common insult (e.g., exposure to an agent suspected of causing disease or a common disease) and are
followed forward from exposure to outcome, and who are disease-free at start of follow-up. Often, at
least one exposed group is compared to one unexposed group, while in other cohorts, exposure is a
continuous variable and analyses are directed towards analyzing an exposure-response coefficient.
Cross-sectional Study—A type of epidemiological study of a group or groups of people that examines
the relationship between exposure and outcome to a chemical or to chemicals at a specific point in time.
Data Needs—Substance-specific informational needs that, if met, would reduce the uncertainties of
human health risk assessment.
Developmental Toxicity—The occurrence of adverse effects on the developing organism that may result
from exposure to a chemical prior to conception (either parent), during prenatal development, or
postnatally to the time of sexual maturation. Adverse developmental effects may be detected at any point
in the life span of the organism.
Dose-Response Relationship—The quantitative relationship between the amount of exposure to a

toxicant and the incidence of the response or amount of the response.
Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to
a chemical; the distinguishing feature between the two terms is the stage of development during which the
effect occurs. Effects include malformations and variations, altered growth, and in utero death.
Epidemiology—The investigation of factors that determine the frequency and distribution of disease or
other health-related conditions within a defined human population during a specified period.
Excretion—The process by which metabolic waste products are removed from the body.
Genotoxicity—A specific adverse effect on the genome of living cells that, upon the duplication of
affected cells, can be expressed as a mutagenic, clastogenic, or carcinogenic event because of specific
alteration of the molecular structure of the genome.
Half-life—A measure of rate for the time required to eliminate one-half of a quantity of a chemical from
the body or environmental media.
Health Advisory—An estimate of acceptable drinking water levels for a chemical substance derived by
EPA and based on health effects information. A health advisory is not a legally enforceable federal
standard, but serves as technical guidance to assist federal, state, and local officials.
Immediately Dangerous to Life or Health (IDLH)—A condition that poses a threat of life or health, or
conditions that pose an immediate threat of severe exposure to contaminants that are likely to have
adverse cumulative or delayed effects on health.

ENDRIN E-3
APPENDIX E
Immunotoxicity—Adverse effect on the functioning of the immune system that may result from
exposure to chemical substances.
Incidence—The ratio of new cases of individuals in a population who develop a specified condition to
the total number of individuals in that population who could have developed that condition in a specified
time period.
Intermediate Exposure—Exposure to a chemical for a duration of 15–364 days, as specified in the

Toxicological Profiles.
In Vitro—Isolated from the living organism and artificially maintained, as in a test tube.
In Vivo—Occurring within the living organism.
Lethal Concentration(LO) (LCLO)—The lowest concentration of a chemical in air that has been reported
to have caused death in humans or animals.
Lethal Concentration(50) (LC50)—A calculated concentration of a chemical in air to which exposure for
a specific length of time is expected to cause death in 50% of a defined experimental animal population.
Lethal Dose(LO) (LDLo)—The lowest dose of a chemical introduced by a route other than inhalation that
has been reported to have caused death in humans or animals.
Lethal Dose(50) (LD50)—The dose of a chemical that has been calculated to cause death in 50% of a
defined experimental animal population.
Lethal Time(50) (LT50)—A calculated period of time within which a specific concentration of a chemical
is expected to cause death in 50% of a defined experimental animal population.
Lowest-Observed-Adverse-Effect Level (LOAEL)—The lowest exposure level of chemical in a study,

or group of studies, that produces statistically or biologically significant increases in frequency or severity
of adverse effects between the exposed population and its appropriate control.
Lymphoreticular Effects—Represent morphological effects involving lymphatic tissues such as the

lymph nodes, spleen, and thymus.
Malformations—Permanent structural changes that may adversely affect survival, development, or

function.
Metabolism—Process in which chemical substances are biotransformed in the body that could result in
less toxic and/or readily excreted compounds or produce a biologically active intermediate.
Minimal Risk Level (MRL)—An estimate of daily human exposure to a hazardous substance that is
likely to be without an appreciable risk of adverse noncancer health effects over a specified route and
duration of exposure.
Modifying Factor (MF)—A value (greater than zero) that is applied to the derivation of a Minimal Risk
Level (MRL) to reflect additional concerns about the database that are not covered by the uncertainty
factors. The default value for a MF is 1.

ENDRIN E-4
APPENDIX E
Morbidity—The state of being diseased; the morbidity rate is the incidence or prevalence of a disease in
a specific population.
Mortality—Death; the mortality rate is a measure of the number of deaths in a population during a
specified interval of time.
Mutagen—A substance that causes mutations, which are changes in the DNA sequence of a cell’s DNA.
Mutations can lead to birth defects, miscarriages, or cancer.
Necropsy—The gross examination of the organs and tissues of a dead body to determine the cause of
death or pathological conditions.
Neurotoxicity—The occurrence of adverse effects on the nervous system following exposure to a

hazardous substance.
No-Observed-Adverse-Effect Level (NOAEL)—The dose of a chemical at which there were no

statistically or biologically significant increases in frequency or severity of adverse effects seen between
the exposed population and its appropriate control. Although effects may be produced at this dose, they
are not considered to be adverse.
Octanol-Water Partition Coefficient (Kow)—The equilibrium ratio of the concentrations of a chemical

in n-octanol and water, in dilute solution.
Odds Ratio (OR)—A means of measuring the association between an exposure (such as toxic substances
and a disease or condition) that represents the best estimate of relative risk (risk as a ratio of the incidence
among subjects exposed to a particular risk factor divided by the incidence among subjects who were not
exposed to the risk factor). An odds ratio that is greater than 1 is considered to indicate greater risk of
disease in the exposed group compared to the unexposed group.
Permissible Exposure Limit (PEL)—An Occupational Safety and Health Administration (OSHA)
regulatory limit on the amount or concentration of a substance not to be exceeded in workplace air
averaged over any 8-hour work shift of a 40-hour workweek.
Pesticide—General classification of chemicals specifically developed and produced for use in the control
of agricultural and public health pests (insects or other organisms harmful to cultivated plants or animals).
Pharmacokinetics—The dynamic behavior of a material in the body, used to predict the fate
(disposition) of an exogenous substance in an organism. Utilizing computational techniques, it provides
the means of studying the absorption, distribution, metabolism, and excretion of chemicals by the body.
Pharmacokinetic Model—A set of equations that can be used to describe the time course of a parent
chemical or metabolite in an animal system. There are two types of pharmacokinetic models: data-based
and physiologically-based. A data-based model divides the animal system into a series of compartments,
which, in general, do not represent real, identifiable anatomic regions of the body, whereas the
physiologically-based model compartments represent real anatomic regions of the body.
Physiologically Based Pharmacodynamic (PBPD) Model—A type of physiologically based dose-

response model that quantitatively describes the relationship between target tissue dose and toxic
endpoints. These models advance the importance of physiologically based models in that they clearly
describe the biological effect (response) produced by the system following exposure to an exogenous
substance.

ENDRIN E-5
APPENDIX E
Physiologically Based Pharmacokinetic (PBPK) Model—A type of physiologically based dose-

response model that is comprised of a series of compartments representing organs or tissue groups with
realistic weights and blood flows. These models require a variety of physiological information, including
tissue volumes, blood flow rates to tissues, cardiac output, alveolar ventilation rates, and possibly
membrane permeabilities. The models also utilize biochemical information, such as blood:air partition
coefficients, and metabolic parameters. PBPK models are also called biologically based tissue dosimetry
models.
Prevalence—The number of cases of a disease or condition in a population at one point in time.
Prospective Study—A type of cohort study in which a group is followed over time and the pertinent
observations are made on events occurring after the start of the study.
Recommended Exposure Limit (REL)—A National Institute for Occupational Safety and Health
(NIOSH) time-weighted average (TWA) concentration for up to a 10-hour workday during a 40-hour
workweek.
Reference Concentration (RfC)—An estimate (with uncertainty spanning perhaps an order of

magnitude) of a continuous inhalation exposure to the human population (including sensitive subgroups)
that is likely to be without an appreciable risk of deleterious noncancer health effects during a lifetime.
The inhalation RfC is expressed in units of mg/m3 or ppm.
Reference Dose (RfD)—An estimate (with uncertainty spanning perhaps an order of magnitude) of the
daily oral exposure of the human population to a potential hazard that is likely to be without risk of
deleterious noncancer health effects during a lifetime. The oral RfD is expressed in units of mg/kg/day.
Reportable Quantity (RQ)—The quantity of a hazardous substance that is considered reportable under
the Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA). RQs are
(1) ≥1 pound or (2) for selected substances, an amount established by regulation either under CERCLA or
under Section 311 of the Clean Water Act. Quantities are measured over a 24-hour period.
Reproductive Toxicity—The occurrence of adverse effects on the reproductive system that may result
from exposure to a hazardous substance. The toxicity may be directed to the reproductive organs and/or
the related endocrine system. The manifestation of such toxicity may be noted as alterations in sexual
behavior, fertility, pregnancy outcomes, or modifications in other functions that are dependent on the
integrity of this system.
Retrospective Study—A type of cohort study based on a group of persons known to have been exposed
at some time in the past. Data are collected from routinely recorded events, up to the time the study is
undertaken. Retrospective studies are limited to causal factors that can be ascertained from existing
records and/or examining survivors of the cohort.
Risk—The possibility or chance that some adverse effect will result from a given exposure to a hazardous
substance.
Risk Factor—An aspect of personal behavior or lifestyle, an environmental exposure, existing health
condition, or an inborn or inherited characteristic that is associated with an increased occurrence of
disease or other health-related event or condition.

ENDRIN E-6
APPENDIX E
Risk Ratio/Relative Risk—The ratio of the risk among persons with specific risk factors compared to the
risk among persons without risk factors. A risk ratio that is greater than 1 indicates greater risk of disease
in the exposed group compared to the unexposed group.
Short-Term Exposure Limit (STEL)—A STEL is a 15-minute TWA exposure that should not be
exceeded at any time during a workday.
Standardized Mortality Ratio (SMR)—A ratio of the observed number of deaths and the expected
number of deaths in a specific standard population.
Target Organ Toxicity—This term covers a broad range of adverse effects on target organs or
physiological systems (e.g., renal, cardiovascular) extending from those arising through a single limited
exposure to those assumed over a lifetime of exposure to a chemical.
Teratogen—A chemical that causes structural defects that affect the development of an organism.
Threshold Limit Value (TLV)—An American Conference of Governmental Industrial Hygienists

(ACGIH) concentration of a substance to which it is believed that nearly all workers may be repeatedly
exposed, day after day, for a working lifetime without adverse effect. The TLV may be expressed as a
Time-Weighted Average (TLV-TWA), as a Short-Term Exposure Limit (TLV-STEL), or as a ceiling
limit (TLV-C).
Time-Weighted Average (TWA)—An average exposure within a given time period.
Toxicokinetic—The absorption, distribution, metabolism, and elimination of toxic compounds in the

living organism.
Toxics Release Inventory (TRI)—The TRI is an EPA program that tracks toxic chemical releases and
pollution prevention activities reported by industrial and federal facilities.
Uncertainty Factor (UF)—A factor used in operationally deriving the Minimal Risk Level (MRL),
Reference Dose (RfD), or Reference Concentration (RfC) from experimental data. UFs are intended to
account for (1) the variation in sensitivity among the members of the human population, (2) the
uncertainty in extrapolating animal data to the case of human, (3) the uncertainty in extrapolating from
data obtained in a study that is of less than lifetime exposure, and (4) the uncertainty in using lowest-
observed-adverse-effect level (LOAEL) data rather than no-observed-adverse-effect level (NOAEL) data.
A default for each individual UF is 10; if complete certainty in data exists, a value of 1 can be used;
however, a reduced UF of 3 may be used on a case-by-case basis (3 being the approximate logarithmic
average of 10 and 1).
Xenobiotic—Any substance that is foreign to the biological system.

ENDRIN F-1
APPENDIX F. ACRONYMS, ABBREVIATIONS, AND SYMBOLS

AAPCC American Association of Poison Control Centers
ACGIH American Conference of Governmental Industrial Hygienists
ACOEM American College of Occupational and Environmental Medicine
ACMT American College of Medical Toxicology
ADI acceptable daily intake
ADME absorption, distribution, metabolism, and excretion
AEGL Acute Exposure Guideline Level
AIC Akaike’s information criterion
AIHA American Industrial Hygiene Association
ALT alanine aminotransferase
AOEC Association of Occupational and Environmental Clinics
AP alkaline phosphatase
AST aspartate aminotransferase
atm atmosphere
ATSDR Agency for Toxic Substances and Disease Registry
AWQC Ambient Water Quality Criteria
BCF bioconcentration factor
BMD/C benchmark dose or benchmark concentration
BMDX dose that produces a X% change in response rate of an adverse effect
BMDLX 95% lower confidence limit on the BMDX
BMDS Benchmark Dose Software
BMR benchmark response
BUN blood urea nitrogen
C centigrade
CAA Clean Air Act
CAS Chemical Abstract Services
CDC Centers for Disease Control and Prevention
CEL cancer effect level
CERCLA Comprehensive Environmental Response, Compensation, and Liability Act
CFR Code of Federal Regulations
Ci curie
CI confidence interval
cm centimeter
CPSC Consumer Products Safety Commission
CWA Clean Water Act
DHHS Department of Health and Human Services
DNA deoxyribonucleic acid
DOD Department of Defense
DOE Department of Energy
DWEL drinking water exposure level
EAFUS Everything Added to Food in the United States
ECG/EKG electrocardiogram
EEG electroencephalogram
EPA Environmental Protection Agency
ERPG emergency response planning guidelines
F Fahrenheit
F1 first-filial generation
FDA Food and Drug Administration
FIFRA Federal Insecticide, Fungicide, and Rodenticide Act

ENDRIN F-2
APPENDIX F
FR Federal Register
FSH follicle stimulating hormone
g gram
GC gas chromatography
gd gestational day
GGT γ-glutamyl transferase
GRAS generally recognized as safe
HEC human equivalent concentration
HED human equivalent dose
HHS Department of Health and Human Services
HPLC high-performance liquid chromatography
HSDB Hazardous Substance Data Bank
IARC International Agency for Research on Cancer
IDLH immediately dangerous to life and health
IRIS Integrated Risk Information System
Kd adsorption ratio
kg kilogram
kkg kilokilogram; 1 kilokilogram is equivalent to 1,000 kilograms and 1 metric ton
Koc organic carbon partition coefficient
Kow octanol-water partition coefficient
L liter
LC liquid chromatography
LC50 lethal concentration, 50% kill
LCLo lethal concentration, low
LD50 lethal dose, 50% kill
LDLo lethal dose, low
LDH lactic dehydrogenase
LH luteinizing hormone
LOAEL lowest-observed-adverse-effect level
LSE Level of Significant Exposure
LT50 lethal time, 50% kill
m meter
mCi millicurie
MCL maximum contaminant level
MCLG maximum contaminant level goal
MF modifying factor
mg milligram
mL milliliter
mm millimeter
mmHg millimeters of mercury
mmol millimole
MRL Minimal Risk Level
MS mass spectrometry
MSHA Mine Safety and Health Administration
Mt metric ton
NAAQS National Ambient Air Quality Standard
NAS National Academy of Science
NCEH National Center for Environmental Health
ND not detected
ng nanogram
NHANES National Health and Nutrition Examination Survey

ENDRIN F-3
APPENDIX F
NIEHS National Institute of Environmental Health Sciences

NIOSH National Institute for Occupational Safety and Health
NLM National Library of Medicine
nm nanometer
nmol nanomole
NOAEL no-observed-adverse-effect level
NPL National Priorities List
NR not reported
NRC National Research Council
NS not specified
NTP National Toxicology Program
OR odds ratio
OSHA Occupational Safety and Health Administration
PAC Protective Action Criteria
PAH polycyclic aromatic hydrocarbon
PBPD physiologically based pharmacodynamic
PBPK physiologically based pharmacokinetic
PEHSU Pediatric Environmental Health Specialty Unit
PEL permissible exposure limit
PEL-C permissible exposure limit-ceiling value
pg picogram
PND postnatal day
POD point of departure
ppb parts per billion
ppbv parts per billion by volume
ppm parts per million
ppt parts per trillion
REL recommended exposure level/limit
REL-C recommended exposure level-ceiling value
RfC reference concentration
RfD reference dose
RNA ribonucleic acid
SARA Superfund Amendments and Reauthorization Act
SCE sister chromatid exchange
SD standard deviation
SE standard error
SGOT serum glutamic oxaloacetic transaminase (same as aspartate aminotransferase or AST)
SGPT serum glutamic pyruvic transaminase (same as alanine aminotransferase or ALT)
SIC standard industrial classification
SMR standardized mortality ratio
sRBC sheep red blood cell
STEL short term exposure limit
TLV threshold limit value
TLV-C threshold limit value-ceiling value
TRI Toxics Release Inventory
TSCA Toxic Substances Control Act
TWA time-weighted average
UF uncertainty factor
U.S. United States
USDA United States Department of Agriculture
USGS United States Geological Survey

ENDRIN F-4
APPENDIX F
USNRC U.S. Nuclear Regulatory Commission

VOC volatile organic compound
WBC white blood cell
WHO World Health Organization
> greater than

≥ greater than or equal to
= equal to
< less than
≤ less than or equal to
% percent
α alpha
β beta
γ gamma
δ delta
μm micrometer
μg microgram
q1 * cancer slope factor
– negative
+ positive
(+) weakly positive result
(–) weakly negative result

CDC 78668 DS1

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Toxicological Profile for

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Each profile includes the following:

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Patrick N. Breysse, Ph.D., CIH

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CONTRIBUTORS & REVIEWERS

CHEMICAL MANAGER TEAM

Interagency Minimal Risk Level Workgroup:

Additional reviews for science and/or policy:

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CHAPTER 1. RELEVANCE TO PUBLIC HEALTH ................................................................................ 1

CHAPTER 2. HEALTH EFFECTS ............................................................................................................. 9

CHAPTER 3. TOXICOKINETICS, SUSCEPTIBLE POPULATIONS, BIOMARKERS, CHEMICAL

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3.4 INTERACTIONS WITH OTHER CHEMICALS ....................................................................... 79

CHAPTER 4. CHEMICAL AND PHYSICAL INFORMATION ............................................................ 81

CHAPTER 5. POTENTIAL FOR HUMAN EXPOSURE ........................................................................ 85

CHAPTER 6. ADEQUACY OF THE DATABASE ............................................................................... 110

CHAPTER 7. REGULATIONS AND GUIDELINES ............................................................................ 119

CHAPTER 8. REFERENCES ................................................................................................................. 121

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1-2. Summary of Sensitive Targets of Endrin – Oral................................................................................... 7

2-2. Levels of Significant Exposure to Endrin – Inhalation....................................................................... 22

2-3. Levels of Significant Exposure to Endrin/Endrin Aldehyde/Endrin Ketone – Oral ........................... 38

3-1. Proposed Metabolism Scheme for Endrin in Mammals ..................................................................... 73

5-1. Number of NPL Sites with Endrin Contamination ............................................................................. 85

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2-1. Health Effects in Humans Exposed to Endrin—Epidemiological Studies ......................................... 13

2-2. Levels of Significant Exposure to Endrin – Inhalation....................................................................... 21

2-3. Levels of Significant Exposure to Endrin/Endrin Aldehyde/Endrin Ketone – Oral ........................... 23

2-4. Levels of Significant Exposure to Endrin – Dermal ........................................................................... 43

2-5. Genotoxicity of Endrin In Vitro .......................................................................................................... 65

2-6. Genotoxicity of Endrin In Vivo........................................................................................................... 67

5-1. Bioconcentration Data for Endrin ....................................................................................................... 91

5-2. Lowest Limit of Detection Based on Standards ................................................................................. 97

7-1. Regulations and Guidelines Applicable to Endrin............................................................................ 119

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CHAPTER 1. RELEVANCE TO PUBLIC HEALTH

1.1 OVERVIEW AND U.S. EXPOSURES

Endrin [2,7:3,6-dimethanonaphth(2,3-b)oxirene, 3,4,5,6,9,9-hexachloro-1a,2,2a,3,6,6a,7,7a-octahydro-

1.2 SUMMARY OF HEALTH EFFECTS

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1. RELEVANCE TO PUBLIC HEALTH

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1. RELEVANCE TO PUBLIC HEALTH

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1. RELEVANCE TO PUBLIC HEALTH

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1. RELEVANCE TO PUBLIC HEALTH

Developmental Effects. Available evidence in humans is inadequate to determine if endrin is associated

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1. RELEVANCE TO PUBLIC HEALTH

1.3 MINIMAL RISK LEVELS (MRLs)

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1. RELEVANCE TO PUBLIC HEALTH

Figure 1-2. Summary of Sensitive Targets of Endrin – Oral

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