Evaluation of estimations in vitro of tissue/blood distribution coefficients for organothiophosphate insecticides.
Physiologically based pharmacokinetic (PBPK) modeling of foreign chemicals is dependent on the accurate determination of their tissue/blood distribution coefficients, Kp (partition coefficients). The present study was undertaken to evaluate the validity of the in vitro estimation of the Kp values of the organothiophosphate insecticides parathion and methyl parathion by equilibrium dialysis. Data derived from previously published studies that utilized single-pass perfusions of mouse livers in situ with parathion or methyl parathion were analyzed to determine liver/perfusate Kp values from the equation Kp = (t 1/2ss) (Q)/(0.693) (VH), where Kp is the liver/perfusate distribution ratio, t 1/2ss is the half-life for approach to steady state of the chemical, VH is the liver volume, and Q is the perfusate flow rate. Kp values for methyl parathion were calculated to be 16.4 +/- 7.5 and 9.5 +/- 2.7 (mean +/- SD) for perfused livers and equilibrium dialysis, respectively, while estimates of Kp for parathion were 15.6 +/- 6.3 and 19.5 +/- 5.5 for perfused livers and equilibrium dialysis, respectively. These results indicate that equilibrium dialysis can be utilized to give an accurate estimate of tissue partitioning of parathion and methyl parathion from perfusate into perfused mouse livers.
Sultatos
L G
LG
Department of Pharmacology and Toxicology, University of Medicine and Dentistry of New Jersey, Newark 07103-2757.
Kim
B
B
Woods
L
L
D000818:Animals; D003956:Dialysis; D008099:Liver / Q000378:metabolism*; D008297:Male; D008743:Methyl Parathion / Q000493:pharmacokinetics*; D051379:Mice; D008954:Models, Biological; D010278:Parathion / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D010477:Perfusion
D008743:Methyl Parathion; D010278:Parathion