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 (14)C, 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, gamma-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.
Tarui
Hirokazu
H
Environmental Health Science Laboratory, Sumitomo Chemical Company, Ltd., 1-98 3-Chome, Kasugade-Naka, Konohana-Ku, Osaka 554-8558, Japan. taruih@sc.sumitomo-chem.co.jp
Tomigahara
Yoshitaka
Y
Matsui
Masayoshi
M
Isobe
Naohiko
N
Kaneko
Hideo
H
Mikami
Nobuyoshi
N
D000818:Animals; D002219:Carbamates / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D005659:Fungicides, Industrial; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D048448:Phenylcarbamates; D051381:Rats
D002219:Carbamates; D005659:Fungicides, Industrial; D048448:Phenylcarbamates; C070961:diethofencarb