The fate of 4-cyano-N,N-dimethylaniline in mice: the occurrence of a novel metabolite during N-demethylation of an aromatic amine.

4-Cyano-N,N-dimethylaniline (CDA), when administered as a single oral dose to mice (18.5 mg/kg), was rapidly absorbed and eliminated. The major route of elimination was the urine (78% dose in 24h). The residues in the tissues 48 h after dosing, as microgram equiv. of CDA/g, were: liver, 0.19; kidney, 0.10; testes, 0.01; fat, 0.10; blood, 0.02. The major metabolite was 2-amino-5-cyanophenyl sulphate, with the N-methyl analogue as a minor metabolite. A novel metabolite, N-acetyl-S-(4-cyanoanilinomethyl)cysteine, was also a significant urinary metabolite, indicating that an electrophilic intermediate is generated during the N-demethylation of CDA. The implications are that N-demethylation may have important toxicological consequences.