The metabolism of chlorotoluron in the rat

The metabolic fate of ¹⁴C-labeled chlorotoluron, i.e., 1-(3-chloro-4-methyl⁴C]-phenyl)-3,3-dimethyl urea, was followed in rats. After a single oral dose the radioactivity was preferably excreted with the urine. Nine of the eleven urinary metabolites isolated, were identified by spectroscopic and derivatization techniques, whereas the structure of the remaining two metabolites was only partially elucidated. N-Demethylation and stepwise oxidation of the ring methyl group to hydroxymethyl and carboxyl derivatives were found as the major metabolic mechanisms. Both mechanisms proceeded simultaneously so that the isolated metabolites showed all combinations of N-demethylation and ring methyl group oxidation in their structures. One of these metabolites was an N-formyl derivative, being probably an intermediate product of demethylation. In the urine of rats fed doses of ¹⁴C]chlorotoluron higher than 50 mg/kg three additional metabolites with different degrees of N-dealkylation were found, the ring methyl group of which was transformed to a methylthio methyl group. The metabolites identified in the faeces were of the same type as those found in the urine. Based on the structures of the metabolites elucidated, a metabolic pathway of chlorotoluron in the rat is presented.