UPTAKE, CLEARANCE, AND METABOLISM OF PARATHION BY PERFUSED WHOLE PIG LIVERS

The uptake, metabolism, and kinetic behavior of parathion were examined in isolated, blood-perfused whole pig liver preparations. First-pass hepatic venous outflow profiles of parathion and 51Cr-labeled red blood cells followed existing transsinusoidal exchange principles. First-pass absorption values for parathion input concentrations of 33.9, 41.0, and 52.8 ppm in the perfusate blood were 97.8, 84.5, and 68.7%, respectively. Second-pass values altered the total absorption of the 41.0 and 52.8 ppm levels to 81.7 and 73.0%. Disappearance of [14C]parathion from blood perfusate was rapid after first pass and by 60-min postaddition to the system, there remained less than 12% of initial input parathion concentrations of 40.2-52.8 ppm. Paraoxon was not detected in two of four trials and in the other two trials, ranged from 2.5 to 9.5% of the added parathion between 20 to 60-min postaddition to the system. Accountability of 14C at 60 min revealed 39.9% in whole blood (31.8% of which was in plasma), 18.9% in liver, and less than 0.6% in 0-60 min bile. Parathion levels in liver and blood averaged 0.61 and 3.26%, respectively, in four trials; paraoxon levels in liver and blood were 3.22 and 4.32%. No p-nitrophenol was detected in liver or blood at any time. Lineweaver-Burk plots of parathion conversion to paraoxon were curvilinear, precluding the determination of kinetic constants for that metabolic reaction. © 1979.