Final Report On the Safety Assessment of 2-Amino-6-Chloro-4-Nitrophenol and 2-Amino-6-Chloro-4-Nitrophenol Hydrochloride1

Abstract

2-Amino-6-Chloro-4-Nitrophenol and its hydrochloride salt are substituted aromatic compounds that function as colorants in hair dyes. Only the hydrochloride salt is currently reported to be used. 2-Amino-6-Chloro-4-Nitrophenol is poorly absorbed through the skin. Less than 0.25% of 2-Amino-6-Chloro-4-Nitrophenol found in a nonoxidative hair dye was absorbed. Less than 0.2% of 2-Amino-6-Chloro-4-Nitrophenol found in an oxidative hair dye was absorbed. In subchronic oral studies in rats, a no observable adverse effect level of 30 mg / kg / day for 2-Amino-6-Chloro-4-Nitrophenol was determined; at higher doses, increased organ weights were seen. A 2% solution of 2-Amino-6-Chloro-4-Nitrophenol applied under occlusive conditions was found to be nonirritating to rabbits. At 0.1%, 2-Amino-6-Chloro-4-Nitrophenol was nonsensitizing; at 2%, there was sufficient skin coloration from the dye that assessment of sensitization was difficult; but no obviously sensitized areas were reported. An oral teratogenicity study in rats showed no birth defects. In one Ames test, Salmonella strains TA97, TA98, and TA100 showed an increase in mutations, with and without metabolic activations. Strain TA1535 was negative, however. In another Ames test, Salmonella strains TA97 and TA100 showed no increase in mutations upon treatment with 2-Amino-6-Chloro-4-Nitrophenol, diluted in dimethylsulfoxide, with and without metabolic activation. Strain TA98 was negative with metabolic activation but positive without activation. In follow-up testing with strain TA98-NR, there was no increase in mutations in the absence of activation. Mutagenicity assays in mammalian systems were negative. The poor absorption through the skin, lack of any teratogenic effect, and negative mutagenesis data in certain Ames test strains and in mammalian systems suggested that any systemic effects from the use of actual products were unlikely. It was possible to conclude that the highest concentration of 2-Amino-6-Chloro-4-Nitrophenol tested (2%) is safe for use in hair dye formulations.