Multivariate modeling of polychlorinated biphenyl-induced CYP1A activity in hepatocytes from three different species: Ranking scales and species differences

Cytochrome P4501A-induced activity of 20 selected polychlorinated biphenyls (PCBs) was evaluated by measuring ethoxyresorufin-O-deethylase and methoxy resorufin-O-demethylase activities induced in the hepatocytes of cynomolgus monkeys, male castrated pigs, and chicken embryos. Quantitative structure- activity relationships have been established, including 52 physicochemical parameters and different measures of the dose-response curves. Relative eff ect potencies are predicted for the 154 tetra-to hepta-PCBs and reported fo r the most potent congeners according to both EC50 and maximal response val ues. Important physicochemical parameters of the PCBs as related to the mod eled activity are parts of their ultraviolet absorption spectra, the Henry' s law constant, the ionization potential, and the octanol-water partition c oefficient. Interspecies differences were found in terms of varied sensitiv ity to different structural subgroups of the compounds. The chicken hepatoc yte assay showed the most specific structure-activity relationship, with hi gh activity for the non-or rho PCBs, whereas the pig hepatocytes responded even for some di- to tetra-ortho PCBs. An interspecies response, the princi pal induction potency, is presented for the 41 most potent PCBs. These resp onses showed strong correlation with the toxic equivalency factors and are likely to be useful in risk assessment of the compounds.