Amended final report of the safety assessment of cocamidopropylamine oxide.

Cocamidopropylamine Oxide is a tertiary amine oxide which functions as a hair-conditioning agent and as a surfactant, currently used in 60 cosmetic formulations at concentrations between 0.07% and 4.0%. In an earlier safety assessment, the Cosmetic Ingredient Review (CIR) Expert Panel had determined that the available data were insufficient to support the safety of this ingredient in cosmetic products. Additional data have now been provided and reviewed. Cocamidopropylamine Oxide was determined to have an acute oral LD(50) between 500 and 1000 mg/kg day(-1) using rats. The acute dermal LD(50) in rats was > 2174 mg/kg day(-1). A 28-day repeated oral dose toxicity study in rats found hemolytic anemia at 150 and 1000 mg/kg day(- 1), with a no observed effect level (NOEL) of 15 mg/kg day(- 1). At 5%, Cocamidopropylamine Oxide solution was not a primary dermal irritant. Application of 81.5% Cocamidopropylamine Oxide to rabbit skin caused moderate irritation under Draize classification scale, but 81.5% Cocamidopropylamine Oxide in rabbit eyes caused severe irritation. A maximization study classified Cocamidopropylamine Oxide as a nonsensitizer to guinea pig skin. Cocamidopropylamine Oxide was not mutagenic in an Ames test, with and without metabolic activation. No evidence of increased chromosomal aberrations were noted in human lymphocytes treated with 81.5% Cocamidopropylamine Oxide. In a clinical study, 7.5% Cocamidopropylamine Oxide was not a sensitizer, although it did produce some reactions typical of mild irritation. Although the impurities, amidoamine and dimethylaminopropylamine, have been implicated in contact allergy reactions to products containing cocamidopropylamine betaine, clinical testing of a product with cocamidopropylamine betaine containing these impurities, at levels comparable to those found in Cocamidopropylamine Oxide, failed to produce a reaction in 10 individuals known to be sensitive to cocamidopropylamine betaine. Two repeat-insult patch tests using a facial wash with 1% raw material containing 35% to 36.5% Cocamidopropylamine Oxide did not find evidence of dermal sensitization. Tests for dermal phototoxicity and photoallergenicity with the same facial wash product also did not produce evidence of effect. The CIR Expert Panel recognizes that there are data gaps regarding the use and concentration of this ingredient. However, the overall information available on types of products in which this ingredient is used and at what concentration indicate a pattern of use, which was considered by the Expert Panel in assessing safety. Overall, these data demonstrate that Cocamidopropylamine Oxide has low toxicity in animal and in vitro tests. Although there are no available carcinogenicity data, the available genotoxicity data, combined with the absence of any structural alerts, suggest no carcinogenic potential. The Panel noted the absence of reproductive and developmental toxicity data. Because this ingredient has a highly polarized molecular structure, the Panel considered that it would be, at most, slowly absorbed. Given that most of the uses and the highest use concentration of 4% is found in rinse-off products, the Panel determined that the available data suggest that Cocamidopropylamine Oxide is safe as used in rinse-off products. Although dermal penetration may be slow, data on the extent of dermal penetration of Cocamidopropylamine Oxide are needed to support the safety of leave-on uses. If there is significant dermal absorption, dermal reproductive and developmental toxicity data may be needed.