Metabolite Screening of Aromatic Amine Hair Dyes Using In Vitro Hepatic Models

The study investigated the potential oxidative metabolism of nine aromatic amine compounds used in hair dyes using human liver microsomes and hepatocytes. Toluene-2,5-diamine (TDA), p-aminophenol, m-aminophenol, p-methylaminophenol, N,N'-bis(2-hydroxyethyl)-p-phenylenediamine, and 1-hydroxyethyl-4,5-diaminopyrazole showed no oxidative metabolism. While oxidized metabolites of 4-amino-2-hydroxytoluene (AHT), 2-methyl-5-hydroxyethylaminophenol (MHEAP), and phenyl methyl pyrazolone (PMP) were detected, they did not exhibit NADPH-dependent covalent binding, indicating they were not reactive. Further studies in human hepatocytes showed conjugation but no oxidative metabolites for AHT, MHEAP, PMP, and TDA. The findings suggested that the tested hair dye ingredients did not undergo hepatic metabolism to form potentially reactive oxidized metabolites.