Mutagens in rat urine after dermal application of 1,3-diaminobenzene.
The mutagenicity of urine from rats treated topically on the skin with 1,3-diaminobenzene was studied by the Salmonella/mammalian-microsome assay. Urine samples were either passed directly through micropore filters or extracts were prepared using XAD-2 resin before testing in the frameshift strain TA98. Significant mutagenic activity was found only after metabolic activation with rat-liver microsomes. The activity was higher in extracts from rats treated with a mixture of hydrogen peroxide and 1,3-diaminobenzene than from rats which were exposed to 1,3-diaminobenzene only. After fractionation of the urine by HPLC it could be demonstrated that the mutagenic activity was not due to the parent amine but related to metabolites in two of the fractions. To a lesser extent these two partially purified fractions were also mutagenic without S9 activation even though it was not possible to demonstrate this effect in unfractionated urine extracts. A third fraction containing two metabolites did not exert demonstrable mutagenic activity. The implications for the assessment of hazard to man are discussed.
D000818:Animals; D001711:Biotransformation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D010655:Phenylenediamines / Q000378:metabolism / Q000494:pharmacology* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D012867:Skin / Q000378:metabolism*
D009153:Mutagens; D010655:Phenylenediamines; C008381:3-phenylenediamine