Final report on the safety assessment of toluene-2,5-diamine, toluene-2,5-diamine sulfate, and toluene-3,4-diamine

Abstract

The diaminotoluenes 2,5-TD, 2,5-TDS, and 3,4-TD are used as colorants in permanent hair dyes and tints. 2,5-TD is used at concentrations up to 1% and 2,5-TDS is used up to 5%. The major routes of excretion after cutaneous absorption by rats were through the urine and feces. The oral LD50 of 2,5-TDS in rats was 98 mg/kg. There was no evidence of percutaneous toxicity to rabbits when 6% 2,5-TDS was applied to intact or abraded skin. In a two-year study, no toxicity was reported in rats receiving biweekly cutaneous applications of formulations containing 3% or 4% 2,5-TD. Mice were also unaffected by 3% 2,5-TDS in an 18-month study, or by 3% 2,5-TD in a two-year study. Rabbits had a slight dermal irritation response after exposure to 2.5% 2,5-TDS, but no irritation occurred in guinea pigs after exposure to 10% solutions of 2,5-TDS or 3,4-TD. 2,5-TD (2.5%) caused mild, transitory conjunctival inflammation in rabbits. The results of sensitization tests of 2,5-TD, 2,5-TDS, and 3,4-TD indicated that each of these diaminotoluenes were sensitizers to laboratory animals and humans. 2,5-TDS was toxic to pregnant rats and their embryos at oral doses of 80 mg kg/day. Doses between 10 and 50 mg/kg day did not cause congenital or maternal abnormalities. o-Toluenediamine, a mixture of 2,3-TD and 3,4-TD (40:60), was not teratogenic when administered orally to rats or rabbits. Cutaneous exposure to hair dye formulations containing 3% 2,5-TDS caused a statistically significant increase in fetal skeletal anomalies in rats. Rats treated with 6% 2,5-TDS did not have this adverse response. In a two-generation reproduction study, mice receiving dermal applications of hair-dye formulations containing either 3% or 6% 2,5-TDS had no signs of pharmacotoxicity, teratogenicity, or reproductive abnormalities. The results cited from various mutagenicity assays of 2,5-TD, 2,5-TDS, and 3,4-TD varied in accordance with the assay system and protocols used. 2,5-TD and 2,5-TDS were noncarcinogenic to rats and mice in both oral and dermal exposure studies. On the basis of the animal and clinical data presented in this report, and the required labeling, it is concluded that Toluene-2,5-Diamine Sulfate and Toluene-3,4-Diamine are safe as cosmetic ingredients in the present practices of use.