Factors affecting the biotransformation of the pesticide parathion by the isolated perfused mouse liver.

Single-pass perfusion of mouse livers in situ with the phosphorothioate pesticide parathion resulted in formation of paraoxon, p-nitrophenol, p-nitrophenyl sulfate, and p-nitrophenyl-beta-D-glucuronide. At a perfusate bovine serum albumin (BSA) concentration of 4% (fraction of unbound parathion = 0.04), and a flow rate of 3.2 ml/min/liver, the half-life associated with the approach to steady state of parathion was 6.2 min (SD = 0.4), whereas at steady state the extraction ratio of parathion was 0.19 (SD = 0.03). Alterations in perfusate flow rates had no discernable effects on metabolism of parathion. However, lowering the BSA perfusate concentration to 1.0% (fraction of unbound parathion = 0.12) significantly prolonged the half-life for the approach to steady state while increasing the steady state extraction ratio to 0.49 (SD = 0.08). At perfusate BSA concentrations below 1%, steady state conditions with respect to parathion could not be achieved during the 50-min perfusions. These results suggest that binding of parathion to BSA hinders its biotransformation by mouse livers perfused in situ, probably by limiting the availability of free pesticide to metabolic sites. Consequently, its elimination by the liver is insensitive to changes in hepatic blood flow. However, exclusion of BSA from the perfusate resulted in partitioning of all parathion in perfusate into the liver, leading to high concentrations of parathion within liver and preventing biotransformation of this pesticide.