To investigate the hepatic metabolism of the new insecticide flupyrazofos [O,O-diethyl O-(1-phenyl-3-trifluoromethylpyrazol-5-yl) phosphorothioate], isolated rat liver was perfused with flupyrazofos under single-pass conditions. In outflow perfusate and bile, 1-phenyl-3-trifluoromethyl-5-hydroxyprazole (PTMHP), PTMHP-sulfate and PTMHP-glucuronide conjugates were identified as the metabolites of flupyrazofos. However, O,O-diethyl O-(1-phenyl-3-trifluoromethylpyrazol-5-yl) phosphate (flupyrazofos oxon) was not detected. A HPLC method with UV detection was used to investigate the hepatic disposition of flupyrazofos and its metabolite PTMHP. The concentrations of flupyrazofos, PTMHP and PTMHP conjugates in outflow perfusate reached steady-state levels within 20 min after commencing perfusion of 7.3 microM flupyrazofos. At steady state, the mean extraction ratio of flupyrazofos was 0.93 (+/- 0.01) and clearance was 26.1 (+/- 0.2) ml min-1 which nearly approached perfusate flow rate (28 ml min-1). PTMHP accounted for 55.7 (+/- 5.8)% of eliminated flupyrazofos and was recovered as unchanged PTMHP, PTMHP-sulfate and PTMHP-glucuronide in the bile as well as the outflow perfusate.
To elucidate the fate of flupyrazofos [O,O-diethyl O-(1-phenyl-3-trifluoromethyl-5-pyrazoyl)phosphorothionate] in soil, an aerobic soil metabolism study was carried out for 60 days with [14C]flupyrazofos applied at a concentration of 0.38 ug g-1 to a loamy soil. The material balance ranged from 103.5% to 86.9% and the half-life of [14C]flupyrazofos was calculated to be 13.6 days. The metabolites identified during the study were 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole (PTMHP) and O,O-diethyl O-(1-phenyl-3-trifluoromethyl-5-pyrazoyl)phosphate (flupyrazofos oxon), with maximum levels of 9.8% and 1.6% of applied radiocarbon, respectively. Evolved [14C]carbon dioxide accounted for up to 5.3% of applied radiocarbon and no volatile products were detected during the study. Non-extractable 14C-residue reached 31.6% of applied material at 60 days after treatment and radiocarbon was distributed almost evenly in humin, humic acid and fulvic acid fraction.
1. The in vitro metabolism of the new insecticide flupyrazofos was studied using rat liver microsomes. Two metabolites were produced and identified as O,O-diethyl O-(1-phenyl-3-trifluoromethyl-5-pyrazoyl) phosphoric acid ester (flupyrazofos oxon) and 1-phenyl-3-trifluoromethyl-5-hydroxypyrazole (PTMHP) based on UV and mass spectral analysis. 2. Cytochrome P450 oxidatively converted flupyrazofos to flupyrazofos oxon, a major metabolite and phenobarbital-induced microsomes increased this desulphuration by 8-fold. 3. Flupyrazofos oxon was converted to PTMHP with a half-life of 47.8 min by chemical hydrolysis and this conversion also proceeded non-enzymatically under our microsomal incubation conditions.
