New Metabolites of Phenthoate in Mammalian Systems

Abstract

Twelve transformation products from phenthoate (PAP)[(CH30)2P(S)SCH(Ph)000C2H5]were identified by using intact mice, rat lliver subcellular fractions and peracid. Other than those previously reported, five products were newly found: (CH30)2P(0)SCH(Ph)000H by mice and microsome-NADPH system (mfo), CH3S(0)CH(Ph)000H by mice, HOCH(Ph)-000C2H5 by mice, mfo and cytosol, (CH3S)(CH30)P(0)SCH(Ph)000C2H5(PAP S-isomer) by mfo and (CH30)2P(0)SSCH(Ph)000C2H5 (phosphinyl disulfide) by peracid oxidation. Based on the identification of the products, the initial modifications seem to occur in five ways on PAP: i) hydrolysis of carboxy ethyl ester; ii) demethylation; iii) formation of phosphorus oxythionate; iv) cleavage of C-S bond; and v) isomerization. Further modifications result in various products. Twenty-three unidentified metabolites were found. PAP S-isomer by mfo and phosphinyl disulfide by peracid oxidation are considered to be produced in mice, but their instability does not allow their finding.