In vitro metabolic clearance of malathion in rats and humans

In vitro intrinsic clearance of malathion was determined in adult and juvenile rat and human liver microsomes. Due to rapid elimination with no detectable levels of the parent, clearance rates of malathion were calculated from formation kinetics of its metabolites: malathion monocarboxylic acid (MMCA) and malaoxon. To correlate in vitro data to in vivo exposure, pharmacokinetics (PK) study was performed in adult rats following a single i.v. (10 mg/kg bw) or oral dose (150 mg/kg bw). The in vitro kinetics data indicate that the metabolic clearance of malathion via formation of MMCA was at the same rate in adult and juvenile human liver microsomes (HLM), but in rat liver microsomes (RLM) the rate was about 10-fold higher in adults compared to juveniles. The rate of formation of malaoxon among the two species and age groups was within 3.5-fold difference. The formation kinetics of malaoxon represented <0.5 % of that observed for MMCA in both rats and humans. As seen in the in vitro results, following i.v. or oral dosing in rats, malathion was not detectable with MMCA being the major metabolite. The kinetics data from this study were useful for the development of a PBPK model for malathion.