Toxicity of Organophosphate and

Organochlorine compounds

BY Supriya Yadav
P-2122
PhD.
• The organophosphates (OPs) are derivatives of
phosphoric or phosphonic acid
• Developed by Schrader
• OPs have replaced the banned organochlorine
compounds and are a major cause of animal
poisoning.
• OPs now used as pesticides (eg, chlorpyrifos,
diazinon, fenitrothion, malathion, parathion, etc)
 Organophosphate toxicity
• Anticholinesterase chemicals- OP
• Cause irreversible inactivation of AChE and
prevention of hydrolysis of Ach by AChE
• Household and industrial insecticides
• Ingestion, dermal contact, or inhalation
• Toxicity- overstimulation of the skeletal
neuromuscular junction, PSNS, and occasionally the
SNS
• Once an OP binds to AChE, the enzyme can undergo one
of the following:

 Endogenous hydrolysis of phosphorylated enzyme by

esterases and paroxonases
 Reactivation by a strong nucleophile like (Pralidoxime)
 Irreversible binding and permanent inactivation of
enzyme (inactivation)
Systems Affected

• Nervous — Muscle tremors and twitching

• Cardiovascular — Bradycardia
• Gastrointestinal — Hypersalivation, vomiting, diarrhea,
and abdominal pain
• Ophthalmic — Miosis, Lacrimation
• Respiratory —severe bronchoconstriction and
bronchorrhea – respiratory distress and life - threatening
hypoxemia.
 CLINICAL FEATURES
• Physical examination -Generalized muscle tremors;
seizures to coma
• Clinical signs of cholinergic effects include DUMBELS
■ D: Diarrhea
■ U: Urination
■ M: Miosis
■ B: Bradycardia/bronchospasm
■ E: Emesis
■ L: Lacrimation
■ S: Salivation

• Bronchospasm and excessive bronchial secretions - life

threatening hypoxemia
Nicotinic effects CNS effects
• Muscle weakness, • Coma
• Respiratory difficulty • Respiratory centre
• Stimulation of SNS depression
• Seizures
• Memory loss
• disorientation
 DIAGNOSTICS
Signalment, historical data & physical examination findings

1. Clinicopathologic data – nonspecific: azotemia, hematuria,

leukocytosis, elevated serum creatine kinase concentration,
hypokalemia, and hyperglycemia

2. Whole blood cholinesterase activity assay

– < 50 percent - suspicious for intoxication
– < 25 percent – confirmatory
 Contd..
. Toxicologic examination Frozen stomach and rumen
contents should be analyzed by GC-MS technique

•  Blood/serum and urine can also be analyzed for residue of

OPs or their metabolites like dimethyl phosphate, diethyl
phosphate, dimethyl thiophosphate,
 Treatment
• 1) muscarinic receptor–blocking agents,
• Atropine sulfate blocks the central and peripheral
muscarinic receptor–associated effects of Ops @ 0.2–2
mg/kg (cats at the lower end of the range), every 3–6 hr
• Dogs @ 2-4mg iv
• For horses and pigs, the dosage is 0.1–0.2 mg/kg, IV,
repeated every 10 min,
• cattle and sheep, the dosage is 0.6–1 mg/kg, one-third
given IV, the remainder IM or SC
•  
 Contd..
• Target end points for atropine therapy.
• Clear chest on ausculatation with no wheeze.
• Heart rate between 80-100 beats/min.
• Pupils no longer pinpoint.
• Systolic blood pressure > 80 mmHg.
• Dry axillae.
 Contd..
2) cholinesterase reactivators,
• cholinesterase-reactivating oxime, 2-pyridine aldoxime
methochloride (2-PAM, pralidoximechloride). The dosage of
2-PAM is 20–50 mg/kg, given as a 5% solution IM or by slow
IV (over 5–10 min)

3) emetics, cathartics, and adsorbents

• Chlorfenvinvos= minimum oral toxic dose appears to be 22
mg/kg for cattle of all ages.
• The acute oral LD50 for rats is 12 mg/kg
• the dermal LD50 in rabbits is 3,200 mg/kg.

• Chlorpyriphos= oral LD50 is 500 mg/kg in goats and 941

mg/kg in rats
• maximum tolerated dose of chlorpyrifos in sheep is 750 mg/kg
(a dose of 1,000 mg/kg was lethal within 30 hours)
• Chlorpyrifos produces reproductive and developmental
toxicity
• Coumaphos is used against cattle grubs 
• Max. conc. that may be safely used on adult cattle, horses, and pigs is
0.5% (Young calves 0.25%)
• MLD for calves appears to be between 10 and 40 mg/kg
• 25 mg/kg is usually fatal in sheep

• Dichlorvos has many uses on both plants and animals

• It is of moderate toxicity, with a minimum toxic dose of 10 mg/kg in
young calves and 25 mg/kg in horses
•  oral LD50 in rats is 25 mg/kg, PO
• dermal LD50 in rabbits is 59 mg/kg. 
• Cats wearing dichlorvos-impregnated collars can develop signs of
ataxia-depression syndrome, followed by death.
• Fenthion is commonly applied topically to control warble
infestation in cattle and fleas in dogs
•  minimum toxic dose, PO, is 25 mg/kg for cattle; 50 mg/kg
is lethal to sheep.
• oral LD50 in rats is 255 mg/kg

• Parathion (diethyl parathion) is widely used for control of

plant pests and is approximately one-half as toxic as
tetraethyl pyrophosphate (TEPP)
• oral LD50 in rats is 3 mg/kg, and the dermal LD50 in rabbits
is 6.8 mg/kg
• Temephos is used as an insecticide against mosquitoes and midges
• oral LD50 for rats is 1 g

• Tetraethyl pyrophosphate (TEPP) is one of the most acutely toxic

insecticides
• One herd of 29 cattle (including calves and adults) was accidentally
sprayed with 0.33% TEPP emulsion; all died within 40 min

• Trichlorfon is used as a systemic insecticide and anthelmintic in

domestic animals.
• tolerated by young dairy calves at 4.4 mg/kg but produces poisoning
at 8.8 mg/kg
• OPs developed initially as pesticides are also used as
anthelmintics

• Malathion is one of the safest organophosphates because

of its selective toxicity; it is highly toxic to insects but
much less toxic to mammalian species (oral LD50 in rats
is 885 mg/kg)
• Also includes toxic nerve gases like tabun, serin, soman
used as toxic agents in chemical warfare
 Intermediate Syndrome

• Organophosphate-induced intermediate syndrome (IMS) has

been seen in people and animals acutely poisoned with a
massive dose of an OP insecticide
• OPs known to cause IMS include chlorpyrifos, diazinon,
dimethoate, disulfoton, fenthion, malathion etc.
• An unclear mechanism
• Characterized by acute paralysis and weakness
• Absence of  muscle fasciculations and hypersecretory
activities
• no specific treatment
 Delayed neurotoxicity of OPC

• Axonopathy due to Neuropathy Targaet Esterases

• Fluorine containing OP compounds like DFP and
triarylphosphates like TOCP (triorthocresylphosphate)
induce delayed NT and cause polyneuropathy,
paralysis, ataxia etc.
 Organochlorine poisoning
• Organochlorine pesticides are organic compounds with
five or more chlorine atoms
• First synthesized pesticides used in agriculture
• Used as contact insecticides; formerly widely used in
agriculture and for domestic purposes, now restricted in
some countries due to recognition of their extreme
persistence in the environment and potential for chronic
toxicity
• Photostable, inert, long residual activity, high
persistence in soil
 Etiology
• accidental ingestion (cattle, dogs) of agricultural products,
• licking out empty drums which previously contained the
chemical;
• inhalation following crop spraying in bad weather,
• using either aerial or ground sprays in the vicinity of
domestic or wild animals;
• incorrect disposal of rinsing water from chemical
containers or spray equipment into rivers and ponds;
• accidental disposal of wood preservatives (containing
pentachlorophenols, and frequently lindane) in water
 Mechanism
• Organochlorines act on the membrane of nerve cells
•  blocking the closure of the ion gates of the sodium
channel during re-polarization
• disrupts the transmission of nervous impulses
• At low concentrations insects suffer from hyperactivity
• At high concentrations they are paralyzed and die
• Affect insect and vertebrates also
• broad spectrum of activity against insects, mites, ticks, etc
• both adulticidal and larvicidal activity, by contact as well as after
oral ingestion
• lipophylic (stored in fat),
Eg.
• AIdrin, chlordane, chlordecone, DDT, dicofol,
dieldrin, dienochlor, endosulfan, endrin, lindane,
perthrane, toxaphene. Lindane is also widely known
as gamma hexachlorocyclohexane (gamma-HCH) or
gamma benzene hexachloride (gammaBHC)
 Toxicity
 Persistent liposoluble compounds which
concentrate in body fat and nervous tissue

 Toxic to the nervous system

 Clinical features
Acute poisoning
• immediate onset of clinical signs with death occurring ,
• accompanied by hyperaesthesia, trembling, convulsions, or
depression (particularly following inhalation exposure).
Characteristic clinical signs include:
• muscular fasciculations of the face and neck followed by
• tremor and shaking, generalized fasciculations;
• salivation; ataxia;
• occasionally agitation, aggression, abnormal postures or behaviour (
• tonic-clonic convulsions with periods of remission, paddling
movements of the legs, hyperaesthesia, opisthotonos and
hyperthermia, which is common at this stage.
Chronic poisoning
(Difficult to diagnose and relatively nonspecific):

• anorexia, weight loss, fall in milk production;

• several episodes of trembling and shaking, persistent
convulsions, deterioration, leading to
• death in several weeks to several months.
 Lesions

Non-specific

In acute poisoning
generalized congestion;
• petechiae on the heart, intestines and lungs;
• oedema of the brain and spinal cord

In chronic poisoning
• degeneration of the liver and kidneys is common
 Treatment
• No antidote.
• Symptomatic care only:
• encourage excretion;
• minimize dermal absorption (wash the skin with soap) and
limit absorption from the gut (adsorbents, gastric lavage);
• cardiorespiratory stimulants;
• control the convulsions: diazepam, xylazine; use barbiturates
with caution as they may depress cardiac and respiratory
functions.
• Organochlorines have two fundamental characteristics:
liposolubility and chemical persistence.
• Resistance of ectoparasites against organochlorines

• Housefly resistance to DDT was already reported in 1947,

and resistance to DDT and other organochlorines
appeared subsequently in numerous parasites (e.g. ticks, 
mosquitoes, fleas, etc.)
 Banned pesticides
• 1970 – Endrin • 1986 – Lindane
• 1976 – DDT • 1987 – HCH (mixed
• 1980 – Chlordimeform Isomers)
• 1980 – Dieldrin • 1987 – Mercury cpds.
• 1980 – Phosphamidon • 1988 – Arsenic (arsenites
• 1980 – Thallium sulpht. and arsenates)
• 1984 – 2,4,5-T • 1988 – Hepatachlor
• 1984 – Ethyl parathion • 1989 – Leptophos
• 1984 – Methyl Captafol
parathion • 1990 –Dichloropropane
• 1986 - Aldrin