S-CHLOROALLYL THIOCARBAMATE HERBICIDES - MOUSE HEPATIC MICROSOMAL L LYSOGENASE AND RAT-METABOLISM OF CIS-[C-14=O]DIALLATE AND TRANS-O]DIALLATE-C-14

Mouse hepatic microsomes metabolize cis- and frarcs-[14C=0] diallate [S-(2, 3-dichloroallyD diisopropylthiocarbamate] in a NADPH-dependent reaction, yielding primarily 14C02 in the absence of glutathione (GSH) and 14C02 and S-(diisopropylcarbamoyl)-GSH in the presence of GSH. Although not detected, sulfoxides of the diallate isomers are likely intermediates in these reactions on analogy with previous studies on S-alkyl and S-benzyl thiocarbamates. Sulfoxides of the diallate isomers are more reactive and thermally unstable than other known thiocarbamate sulfoxides. The finding of carbonyl sulfide as a in vitro metabolite suggests that α-carbon hydroxylation of the 2, 3-dichloroallyl group is an additional pathway for diallate degradation. Rats administered either diallate isomer excrete the S-diisopropylcarbamoyl derivatives of mercapturic acid (62%), cysteine (7%), and mercaptoacetic acid (1.5%) in addition to 14CO2 (20%). The principal metabolic pathway in rats appears to involve sulfoxidation, nonenzvmatic reaction of the sulfoxide with GSH, and mercapturic acid formation. © 1979, American Chemical Society. All rights reserved.