USING STRUCTURAL INFORMATION TO CREATE PHYSIOLOGICALLY-BASED PHARMACOKINETIC MODELS FOR ALL POLYCHLORINATED-BIPHENYLS .1. TISSUE-BLOOD PARTITION-COEFFICIENTS

Physiologically based pharmacokinetic (PBPK) models are useful in desc ribing the distribution, metabolism, and fate of xenobiotics across mu ltiple species. The eventual goal of the present research is to create PBPK models for all 209 polychlorinated biphenyls (PCBs). Keys parame ters in any PBPK model are the tissue-to-blood partition coefficients. Tissue:blood partition coefficients relate the compound's concentrati on in a target tissue to its concentration in blood under equilibrium conditions. Data on the adipose:plasma partition coefficients of 24 PC Bs were used in a regression analysis to find an expression for the ad ipose:plasma partition coefficient as a function of molecular structur e. Using stepwise regression, it was found that three simple structura l descriptors were sufficient to predict adipose:plasma partition coef ficients for all 209 PCB congeners. Data on the distribution of PCBs a mong blood components were used to derive the adipose:blood partition coefficient from the adipose:plasma partition coefficient. The lipid c ontents of li, er. muscle, and skin were used to derive the tissue:blo od partition coefficient for those tissues from the adipose:blood part ition coefficient. These results allow for the calculation of tissue:b lood partition coefficients for liver, skin, muscles, and fat for all 209 PCB congeners. (C) 1997 Academic Press.