The effect of O,S,S,-trimethyl phosphorodithioate on the in vivo metabolism of phenthoate in the rat

The in vivo metabolism of phenthoate (O,O-dimethyl S-[α-(carboethoxy)benzyl]phosphorodithioate) was followed in rats after oral administration of a nontoxic dose of 100 mg/kg. The same metabolic study was conducted following coadministration of 0.5% O,S,S-trimethyl phosphorodithioate (OSS-Me). When administered alone, phenthoate was metabolized principally by carboethoxy ester hydrolysis and cleavage of the PO and CS bonds, resulting in at least six metabolites. The primary urinary metabolite excreted was phenthoate acid. Coadministration of 0.5% OSS-Me did not alter the types of metabolites excreted. However, a reduction of the carboxylesterase-catalyzed product (phenthoate acid) was observed, indicating that the enzyme responsible for the major pathway of phenthoate detoxication was inhibited. Alternate detoxication processes did not compensate for the reduction in carboxylesterase-catalyzed detoxication. It was concluded that inhibition of the carboxylesterase enzymes is the major cause of the potentiation of phenthoate toxicity by OSS-Me.     

Metabolism of the methoxychlor isostere,dianisylneopentane, in mouse,insects, and a model ecosystem

Dianisylneopentane or 1,1-bis(p-methoxyphenyl)-2,2-dimethylpropane was metabolized largely by O-demethylation to form mono- and diphenol derivatives. Only a small percentage was degraded by α-hydroxylation and rearrangement. In the model ecosystem, dianisylneopentane reacted very similarly to methoxychlor, accumulating in fish to about the same extent and yielding a slightly higher ratio of polar to nonpolar metabolites. The neopentyl group proved to be approximately as stable in biological systems as the isosterically equivalent trichloromethyl group.     

Cytochrome P-450 in insects. 7. Age dependency and phenobarbital induction of cytochrome P-450, P-450 reductase,and monooxygenase activities in the black blow fly (Phormia regina,Meigen)

Development and phenobarbital (PB) induction of microsomal cytochrome P-450, NADPH-cytochrome c (P-450) reductase, two epoxidation, and two O-demethylation activities were examined in chronologically timed populations of female black blow flies (Phormia regina, Meigen). Measurements of these enzymes started with the pharate adult stage and ended 5 days following eclosion. Induction occurred in all enzymes, even at 0.005% PB, and was maximum at 0.15%. Dramatic induction of the O-demethylation of 7-methoxy-4-methylcoumarin was observed in flies dosed with the maximum concentration of the drug. This monooxygenase activity increased to nearly 1400 times the level in control flies, whereas the other O-demethylation (methoxyresorufin) and the two epoxidation reactions exhibited considerably less change. Induction of the structural enzymes of this enzyme system were 10-fold for cytochrome P-450 and 5-fold for NADPH-cytochrome c (P-450) reductase. These data suggest that PB induces several P-450's in the blow fly, particularly one bearing a high degree of specificity for 7-methoxy-4-methycoumarin.