A PARTITION-COEFFICIENT DETERMINATION METHOD FOR NONVOLATILE CHEMICALS IN BIOLOGICAL TISSUES

Partition or distribution coefficients are critical elements in effort s designed to describe the uptake, distribution, biotransformation, an d excretion of organic chemicals in biological systems. In order to es timate the partition coefficients needed to describe the biological di stribution of low-volatility compounds, an experimental method was dev eloped to measure partitioning of nonvolatile compounds into biologica l tissues. Blood, fat, muscle, liver, and skin were individually incub ated in a saline solution containing the chemical of interest. Each sa mple was centrifuged and 2.0 mL of the supernatant was removed and pla ced into a prewashed, low binding 10,000 MW cutoff Millipore filter ce ll. Each cell was fitted with a magnetic stirrer and 32 psi nitrogen w as applied to the closed cell. The filtrate was collected, extracted, and analyzed for the chemical of interest. The chemicals evaluated wer e parathion, lindane (hexachlorocyclohexane), paraoxon, perchloroethyl ene, trichloroacetic acid, and dichloroacetic acid. These chemicals we re chosen to develop this method because their vapor pressures range f rom 9 X 10(-6) to 14.2 mm Hg at 20 degrees C. For the one volatile che mical evaluated, perchloroethylene, the method provided partition coef ficient results that were in good agreement with values obtained using the vial equilibration method. The nonvolatile partition coefficient method described in this paper demonstrates an approach for evaluation of chemicals with diverse chemical structure and solubility propertie s. (C) 1994 Society of Toxicology.