Final Report on the Safety Assessment of Chloroacetamide

Abstract

Chloroacetamide is a chlorinated aliphatic amide used as a preservative in U.S. cosmetic formulations at concentrations of less than or equal to 1.0%. The antimicrobial spectrum for certain test microorganisms required concentrations up to 0.3% for minimal inhibition and 0.5% for a minimal germicidal effect. The acute oral LD50 for this compound was 155 mg/kg for mice,70 to 138 mg/kg for rats, 31 mg/kg for dogs, and 122 mg/kg for rabbits. Chloroacetamide was neither an ocular nor a skin irritant when tested at 5.0% in the rabbit. No sensitization was reported in three separate studies using guinea pigs at test concentrations of 0.07%, 0.21%, and 1.0%. In a 13-week subacute oral study in rats, Chloroacetamide at concentrations of 12.5 and 50 mg/kg produced testicular atrophy but no other observable external effects. In a 90-day oral toxicity study in rats, Chloroacetamide at concentrations of 500 mg/kg produced an increase in leukocytes. In a teratogenic study, Chloroacetamide was toxic at a dose of 50 mg/kg but did not produce teratomas in the surviving young rats. Chloroacetamide was nonmutagenic in the Ames assay, both with and without activation, in a micronucleus study, and in dominant lethal assays. In predictive RIPT sensitization studies, Chloroacetamide was a human sensitizer at concentrations of 0.5% and 1.25%. A third RIPT study on 150 subjects confirmed the sensitization results at 0.5%. Based on the data included in this report and the reconfirmation that Chloroacetamide is a potential human sensitizer at use concentrations, it is concluded that Chloroacetamide is unsafe for use as a cosmetic ingredient.