Final Report on the Safety Assessment of 2,4-Diaminophenol and 2,4-Diaminophenol Dihydrochloride

Abstract

The aromatic amines 2,4-Diaminophenol and 2,4-Diaminophenol Dihydrochloride are colorants intended for use in oxidative hair dyes. Currently, 2,4-Diaminophenol Dihydrochloride is used in three hair dyes, whereas there are no reported uses of 2,4-Diaminophenol. Chromatographic analysis of 2,4-Diaminophenol indicates that an impurity, 2-amino-4-nitrophenol, is present at a concentration of 2.7%. The oral median lethal dose (LD50) for 2,4-Diaminophenol Dihydrochloride in rats was 0.24 g/kg, with a dose-dependent renal toxicity seen in acute, short-term, subchronic and chronic toxicity tests. Renal toxicity was noted in rats at doses nine times lower than the LD50. 2,4-Diaminophenol Dihydrochloride was a skin and ocular irritant in rabbits, but not in guinea pigs, nor did it induce sensitization in guinea pigs. A dye formulation with 0.2% 2,4-Diaminophenol did not produce evidence of terato-genesis in female rats. No genotoxicity was seen in some systems, but there was evidence of mutagenesis in others. Dermal application of 2,4-Diaminophenol was not carcinogenic in Swiss Webster mice in a 23-month study, even with the presence of a 2.7% 2-amino-4-nitrophenol impurity. Administration of 2,4-Diaminophenol Dihydrochloride by gavage produced no evidence of carcinogenic activity in National Toxicology Program bioassays in male and female F344/N rats and female B6C3F1 mice. There was an increase in renal tubular cell adenomas in male B6C3F1 mice at the highest dose level, 38 mg/kg. On the basis of the animal data presented in the report, the expected use of the product, and acknowledging the labeling requirements for hair dyes if they are to qualify for an exemption from the Food and Drug Administration, it is concluded that 2,4-Diaminophenol and 2,4-Diaminophenol Dihydrochloride are safe for use in hair dyes at concentrations up to 0.2% (as the free base).