Final Report on the Safety Assessment of HC Red No. 71

HC Red No. 7 functions as a semipermanent (direct) hair colorant in one cosmetic product at 1%. Analytical studies found the relative purity of HC Red No. 7 to be >98.5%. Impurities may include 2-nitro-benzene-1,4-diamine; 3-(4-amino-3-nitro-phenyl)oxazolin-2-one; 2-chloroethyl 4-amino-3-nitrophenylcarbamate; residual solvents ethanol, DMF, or isopropyl acetate; chloride ions; and heavy metals. Around 0.10% of the applied HC Red No. 7 was absorbed in human dermatomed skin samples. In an acute oral toxicity study in rats, the maximum nonlethal dose was 300 mg/kg. The no observed effect level (NOEL) in a subchronic oral toxicity study in rats was 50 mg/kg day-1 . HC Red No. 7 was not a dermal or ocular irritant in rabbits, but lymphoproliferative responses in mice indicated that HC Red No. 7 should be considered a moderate sensitizer. The NOEL for maternal toxicity was 50 mg/kg/day and the no observed adverse effect level (NOAEL) for embryonic development was 200 mg/kg/day in a prenatal toxicity study of HC Red No. 7 using rats. HC Red No. 7 was nonmutagenic at the hprt locus but mutagenic at the TK locus in mouse lymphoma cells, was mutagenic in several Salmonella typhimurium strains, was not active in an unscheduled DNA synthesis assay, and was unclear in a micronucleus assay in human lymphocyte cultures. No carcinogenicity studies were available, nor were any clinical tests reported. Available hair dye epidemiology studies are insufficient to conclude a causal relationship between hair dye use and cancer or other diseases, but more relevant is that direct hair dyes, although not the focus in all investigations, appear to have little evidence of an association with adverse events as reported in epidemiology studies. As reviewed by the Cosmetic Ingredient Review (CIR) Expert Panel, HC Red No. 7 appears to be a moderate sensitizer in animals. No human sensitivity data concerning this ingredient have been reported. However, hair dyes containing HC Red No. 7, as coal tar hair dye products, are exempt from the principal adulteration provision and from the color additive provisions in sections 601 and 706 of the Federal Food, Drug, and Cosmetic Act, when the label bears a caution statement and patch test instructions for determining whether the product causes contact dermatitis. The Expert Panel expects that following this procedure will identify prospective individuals who would have an irritation/sensitization reaction and allow them to avoid significant exposures. The CIR Expert Panel also noted that mutagenicity studies available for HC Red No. 7 gave both positive and negative results. Based on the available data, it was concluded that, at most, this ingredient is a weak mutagen. Due to its low dermal absorption potential and its use as a semipermanent hair dye, the CIR Expert Panel believes there is low risk of genotoxicity and that HC Red No. 7 is safe as a hair dye ingredient in the practices of use and concentrations as described in this safety assessment.