Metabolism of Diethofencarb (Isopropyl 3,4-Diethoxyphenylcarbamate) in Rats:  Identification of Metabolites in Urine

Rats were orally given a diethofencarb (isopropyl 3,4-diethoxyphenylcarbamate) labeled with 14C, at 300 mg/kg/day, for 4 consecutive days, and 11 metabolites in urine were purified by a combination of several chromatographic techniques. The chemical structures of all isolated metabolites were identified by spectroanalyses (NMR and MS). Ten of them were newly identified forms. Five of them were S-conjugates: three mercapturic acid conjugates, one S-methyl conjugate, and one SO-methyl conjugate. The others were two phenoxyacetic acids, hydroxyacetanilide, hydroxyisopropyl carbamate, and oxazolinone derivatives. From the results, the existence of the following reactions in rats can be concluded: (1) deethylation of the 4-ethoxy group; (2) conjugation of phenols with glutathione, γ-glutamyltranspeptidation and depeptidation of the glutathione to form cysteine conjugates, and N-acetylation of the cysteine; (3) cleavage of the C−S linkage of cysteine conjugates followed by methylation; (4) oxidation of the S-methyl group; (5) cleavage of the carbamate linkage; (6) acetylation of the resultant amino group; (7) oxidation of the acetyl group; (8) oxidation of the isopropyl group; (9) cyclization of the oxidized isopropyl carbamate group; and (10) oxidation of the 4-ethoxy group. Keywords: Metabolism; rat; fungicide; identification; biotransformation; conjugation; mercapturic acid