FURTHER METABOLISM OF NAPHTHYL N-METHYLCARBAMATE (CARBARYL) BY THE INTESTINE

Metabolism of the insecticide (14C-naphthyl) N-methylcarbamate by the rat small intestine was observed in vitro. Volatile derivatives of the intact 14C-metabolites or of the 14C-labeled hydrolysis products (14C-lipophiles) from metabolites were analyzed by gas-liquid chromatography (glc) interfaced to a mass spectrometer (glc/ms). Of the 1.75 mg of substrate equivalents of 14C-labeled material recovered, approximately 43% was the unmetabolized 14C-carbamate; [1-14C]naphthyl glucuronide and [14C]hydroxy-1-naphthyl glucuronide accounted for about 23%. The rest (about 34%; 0.59 mg-eq) was distributed among numerous identified and unidentified 14C-lipophiles derived from polar 14C-metabolites. The following 14C-lipophiles were identified: 1-naphthyl N-methylcarbamate, hydroxy-1-naphthyl N-methylcarbamate, 1-naphthol, hydroxy-1-naphthol, dihydroxy-1-naphthol (tentative), and dihydro-dihydroxy-1-naphthol. The evidence indicates that the same 14C-lipophile was released by hydrolysis of several 14C-metabolites; presumably, the hydrophilic groups were cleaved from the lipophile of these metabolites unintentionally during chromatgraphy and preparation of volatile derivatives. Glucuronic acid was the only hydrophile identified. Thus, the small intestine was capable of metabolism of this carbamate involving oxidations of the naphthol moiety, hydrolysis of the carbamate esters, and conjugations of the carbamate and of lipophilic products derived from the carbamate. Trimethylsilyl derivatives were found to be useful for glc and glc/ms analyses of the metabolites of this carbamate. © 1979.