PRODUCT ALLERGEN WATCH

Cocamidopropyl Betaine
Sharon E. Jacob and Sadegh Amini

Cocamidopropyl betaine (CAPB) is an amphoteric synthetic detergent that has been increasingly used in cosmetics and personal
hygiene products (eg, shampoos, contact lens solutions, toothpaste detergents, makeup removers, bath gels, skin care products,
cleansers, liquid soaps, antiseptics, and gynecologic and anal hygiene products) because it induces relatively mild skin irritation.
Delayed T-cell–mediated type IV hypersensitivity reactions to CAPB have been reported, and contact sensitization prevalence is
estimated at between 3.0 and 7.2%. The increasing rates of sensitization led to CAPB’s being named Allergen of the Year in 2004.
Related impurities rendered during the manufacturing process (such as amidoamine and dimethylaminopropylamine) are thought to
play a role in sensitization.

ISTORICAL RECORDS depict the importance, ordinary people.1,2 Several soapmakers arrived from
H development, and evolution of soaps and detergents.
Inscriptions on clay containers found in Babylon (2800 BC)
England and began commercial soapmaking in the United
States in the early 1600s. The outbreak of the American
represent ancient evidence of soapmaking from fats and Civil War in 1861 underscored the importance of soap in
ashes, and the Ebers papyrus from Egypt (1500 BC) further preventing wound infections and brought the knowledge
describes the process of combining animal and plant oils of soapmaking to thousands of Americans.2,3
with alkaline salts to treat diseases and assist bathing.1–3
Moses gave the Israelites precise personal cleanliness rules
related to health and religious purification.1 Furthermore, Soaps and Surfactants
from 312 BC to the sixth century AD, the Roman baths and
aqueducts became so popular throughout the Roman The advantages of synthetic detergent soap products
Empire that soap factories were formed to keep up with gradually led to their overwhelming popularity over
the demand for soap. An entire soapmaking factory, soaps.5–8 By 2003, soap accounted for only 9 million of
along with bars of soap preserved in hardened lava, was the more than 27 million tons of detergents and soap used
found in archeological excavations in Pompeii, Italy.4 After worldwide each year.1–3 Detergents, by definition, contain
the fall of the Roman Empire in 476 AD, the habits of surfactants (surface-active agents), which are thought to
bathing and washing almost disappeared because of a lower the water surface tension. These are combined with
superstitious fear that water would dilate the pores and two other chemical properties needed for washing: thermal
expose the organs to disease.2 This created a poor health energy (warm or hot water) and mechanical energy
environment during the Middle Ages, when numerous (agitation by hand or machine).1,9,10
plagues developed (including the fourteenth century’s Surfactants are classified by their ionic properties in
‘‘Black Death’’). water as anionic, cationic, nonionic, or amphoteric
(zwitterionic). They can cause variable amounts of damage
In the seventh century, Arab traders brought soaps
to the skin barrier, depending on the hydrogen ion
to Europe, and by the twelfth century, every European
concentration (pH) of the cleanser and their ionic and
city was a soap producer.1,2 Soap was heavily taxed as a
structural interactions with skin surface proteins.
luxury item until the nineteenth century, when the tax
Erythema, irritation, postwash tightness, dryness, and
was considerably lowered and soap became available to
itching are all consequences of damage to keratin,
membrane proteins, and the lipid bilayer (either directly
or indirectly).11–13 The amphoteric surfactants (of which
From the Department of Dermatology, University of Miami School of the betaines are typical examples) contain both negatively
Medicine, Miami, FL. and positively charged elements within the same molecular
Reprints not available. structure and thus allow for cationic or anionic activity in
DOI 10.2310/6620.2008.06043 a shorter range of pH levels, avoiding both extremes.5,6,14

Dermatitis, Vol 19, No 3 (May/June), 2008: pp 157–160 157

Thus, these detergents are milder than the anionic Administration’s Voluntary Cosmetic Registration
surfactants on the skin and produce significantly less Program.18,19,22 From 1995 to 2001, CAPB was ranked
eye-irritant effects.5,14,15 twenty-ninth among the top fifty most common allergens
Cocamidopropyl betaine (CAPB) is the most notable detected in patch tests,23 and contact sensitization rates for
zwitterionic (amphoteric) ammonium-containing surfac- CAPB have been reported at between 3.0 and 7.2%.18,19,24
tant.14,16 Originally introduced into personal hygiene Because of the increased prevalence of contact sensitiza-
products by Johnson & Johnson in 1967 as the ‘‘No tion, CAPB was designated Allergen of the Year by the
More Tears’’ ingredient in children’s shampoos,17 CAPB is American Contact Dermatitis Society in 2004,25 high-
compounded by reacting fatty acids (obtained from lighting the importance of screening for this allergen in the
coconut oil) with dimethylaminopropylamine (DMAPA), evaluation of the patient with contact dermatitis.
producing cocamidopropyl dimethylamine, a derived Since the first report of allergy to CAPB in 1983,26 there
amidoamine (AA). The amidoamine is then processed have been many reports of allergic contact dermatitis
with sodium monochloroacetate to obtain the end (ACD) from shampoos,20,26–29 contact lens solutions,29
product, CAPB.18,19 (See synonyms for CAPB, Table 1). toothpaste detergents,30 makeup removers,31 bath gels,19
CAPB contains an anionic group (carboxylic group) skin care products, cleansers, liquid soaps, antiseptics, and
and a cationic group (quaternary ammonium group).19 gynecologic and anal hygiene products.18 The increase in
The lipophilic group is formed by a mixture of coconut contact sensitization prevalence is due to more frequent
fatty acids with chain lengths varying between C-8 and C- use as CAPB was substituted for anionic surfactants (such
18. This means that CAPB is a mixture of several as sodium lauryl sulfate) and cationic surfactants (such as
compounds with the same basic structure and different polyoxyethylene dihydroxypropyl linoleaminium chlor-
lipophilic ends. Commercial products also contain other ide), which are much more irritating.11,18,20,32
substances, such as free fatty acids and sterols.19,20 The In addition, CAPB has been reported to cause mild
purpose of the addition of CAPB to personal hygiene irritant contact dermatitis12 although its recognition as a
products is as a foam booster, thickener, and mildness more capable contact sensitizer causing ACD is widely
enhancer.21 accepted.25,31 When patch-testing for CAPB, it is important
to be aware of the possibility of irritant reactions character-
ized by mild erythema that usually disappears in 24 to 48
CAPB as an Allergen
hours.31 To avoid overreading irritant false-positive patch-
The use of CAPB in cosmetics and personal hygiene test reactions, it is important to perform a delayed reading of
products has increased exponentially since the 1970s.10 Of the test site at 96 hours.31 Furthermore, the process of
the 19,000 cosmetic products registered in 1980, 47 manufacturing CAPB results in numerous reactants and
contained CAPB. By October 2005, 1,242 of 22,016 intermediates, such as DMAPA and AA, that could remain in
products were listed as containing CAPB, representing a the final product and cause sensitization.16,19,33
2,250% increase according to the Food and Drug Several studies have demonstrated that the real sensitizers
may in fact be these contaminant chemicals (DMAPA and
AA), rather than CAPB itself.18,19,24,33,34 The issue of the real
Table 1. Synonyms for Cocamidopropyl Betaine sensitizer has been a matter of controversy for many
years.24,25,35 Numerous American studies demonstrated that
1-Propanaminium 3-amino-N-(carboxymethyl)-N,N-dimethyl-
N-coco acyl derivs, hydroxides, inner salts
AA was the cause of the ACD24,36,37 whereas numerous
Cocamidopropyl betaine European studies demonstrated that DMAPA was the
Cocoamidopropylbetaine sensitizer.34,38 Foti and colleagues sought to determine the
Coconut oil amidopropyl betaine role of DMAPA and AA in contact allergy to CAPB. To verify
Cocoyl amide propyldimethyl glycine the possibility that pure AA had a sensitizing role in subjects
N-(3-Cocoamidopropyl)-N,N-dimethyl-N- with positive reactions to CAPB, they tested 10 patients with
carboxymethylammonium hydroxide, inner salt contact allergy to commercial CAPB with DMAPA 1%
N-(3-Cocoamidopropyl)-N,N-dimethyl-N-carboxymethyl betaine aqueous and with pure AA in concentrations of 0.5 to 0.1%
N-Cocamidopropyl-N,N-dimethylglycine, hydroxide, inner salt aqueous and found that all patients who had positive
N-(Cocoamidopropyl)-N,N-dimethyl-N-carboxymethyl ammonium, reactions to DMAPA reacted to AA 0.5% and 0.25%
betaine
aqueous. Notably, 4 of the 10 subjects also had positive
Tegobetaine L7
reactions to AA 0.1% aqueous. The investigators concluded
 Cocamidopropyl Betaine 159

that the DMAPA was indeed the true sensitizing substance 2. Proctor & Gamble. History of washing. 2000, 2001. Available at:
whereas AA, which may release DMAPA in vivo by http://www.scienceinthebox.com (accessed March 26, 2006).
3. Kostka KL, McKay DD. Chemists clean up: a history and
enzymatic hydrolysis, was implicated in the transepidermal
exploration of the craft of soapmaking. How soap came to be
penetration of this sensitizing agent.38 common in America. J Chem Educ 2002;79:1172–5.
Furthermore, CAPB with minimal levels of the inter- 4. Carol Ochs, Simply Soap. History of soapmaking. 1994. Available
mediary impurities and manufactured specifically for perso- at: http://www.simplysoap.com/History%20of%20Soapmaking.htm
nal care and health care products has demonstrated a very low (accessed April 3, 2006).
5. Royal Society of Chemistry. Surfactants: the ubiquitous ampho-
number of reactions in patch testing, even in patients who
philes. 2004. Available at: http://www.chemsoc.org/chembytes/
previously had positive reactions to CAPB.11,12,24,38 These ezine/2003/hargreaves_jul03.htm (accessed March 26, 2006).
results show the importance of recognizing variations in the 6. Columbia Electronic Encyclopedia. Detergent. 2000–2005. Available
manufacturing and supplying of the products in different at: http://www.infoplease.com/ce6/sci/A0815306.html (accessed Oct
regions and the need to be aware that all three allergens may 8, 2005).
be important.18,36 The North American Contact Dermatitis 7. Huntington SJ. The mystery and history of soap. 2005. Available at:
http://www.csmonitor.com/2003/0513/p18s02-hfks.html (accessed
Group has switched to routinely testing patients with both
Sep 23, 2005).
CAPB and AA36 whereas some of the European group 8. Campbell LA, Campbell HA. Development of the detergent
investigators have recommended that testing with CAPB be industry. 1998–2005. Available at: http://www.chemistry.co.nz/
suspended,38,39 calling for higher-quality purification and for deterghistory.htm (accessed Apr 2, 2006).
‘‘removing sensitization potential.’’ 9. Proctor & Gamble. Natural and synthetic surfactants. 2000, 2001.
CAPB was one of 408 cosmetic ingredients found ‘‘safe, Available at: www.scienceinthebox.com (accessed Mar 26, 2006).
10. Soap and Detergent Association. Soaps and detergents chemistry.
with qualifications’’ by the Cosmetic Ingredient Review
Available at: (http://www.cleaning101.com/cleaning/chemistry/
(CIR) Expert Panel in December 2005.40 The CIR Expert (accessed Apr 3, 2006).
Panel recommended that CAPB is safe as used in rinse-off 11. Barany E, Lindberg M, Loden M. Biophysical characterization of
products, the concentration of use for products designed skin damage and recovery after exposure to different surfactants.
to remain on the skin for prolonged periods of time should Contact Dermatitis 1999;40:98–103.
not exceed 3%. Also, the Material Safety Data Sheet 12. Ananthapadmanabhan KP, Moore DJ, Subramanyan K, et al.
Cleansing without compromise: the impact of cleansers on the skin
recommendation is to minimize contact.41
barrier and the technology of mild cleansing. Dermatol Ther 2004;
Clinically, CAPB contact sensitization typically presents 17 Suppl 1:16–25.
as a chronic relapsing dermatitis that predominantly 13. Vilaplana J, Mascaro JM, Trullas C, et al. Human irritant response
affects the head (scalp, face, eyelids) and neck. There are to different qualities and concentrations of cocoamidopropylbe-
reported cases of occupational ACD in hairdressers and of taines: a possible model of paradoxical irritant response. Contact
Dermatitis 1992;26:289–94.
health care workers’ being sensitized on the lower arms
14. Somasundaran P, Zhang L, Anjing L. Surfactants and interfacial
and hands.18,20,31,37 Importantly, more-diffuse presenta- phenomena in cosmetics and detergency. Cosmetics Toiletries 2001;
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body washes, shampoos, and bath gels, especially among 15. Expert Panel of the American College of Toxicology. Final report on
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16. Peter C, Hoting E. Contact allergy to cocamidopropyl betaine
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of the T.R.U.E Test slated to be released in 2008.42
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