The production and use of polychlorinated biphenyls (PCBs) has been banned in the US for over 20 years. However, due to their extreme persistence in the environment, their insolubility in water, and their adsorption onto soil particles, environmental and human exposure continues to be a matter of concern. It is speculated that, due to the transport of PCBs on dust particles, the current primary route of exposure of most of the population to PCBs is dermal. Studies of the dermal absorption of PCBs have established that bioavailability following dermal exposure is highly dependent upon the degree and position of chlorination. The less chlorinated congeners are much more bioavailable than the more highly chlorinated congeners. Within a group, e.g., tetrachlorobiphenyls, bioavailability varies with the position of chlorination. Those congeners having chlorine atoms in the para position are less readily absorbed from the skin. Data developed in this work have been used to construct a model that predicts the fate of the complex mixtures of PCBs found in the environment. In the course of these studies an additional line of research was developed to address the estrogenicity of catechol metabolites of PCBs. When cultured HeLa cells transfected with the estrogen reporter gene ERET81CAT were incubated with PCB catechols the responses elicited fell within the range of effects measured for other environmental estrogens, e.g., nonylphenol and o,p-DDT. Again, structural considerations play a major role in the biological effects of the respective metabolites. Whereas 2,4-catechols showed virtually no activity the activity of the 3,4-catechols increased with the degree of chlorination. In support of these studies, methods were developed for the synthesis of PCB catechols in quantities sufficient for more extensive studies. Studies of the effect of these synthetic metabolites in in vitro systems demonstrated that PCB catechols are potent inhibitors of catechol O- methyltransferase (COMT). This is of particular relevance because it is this enzyme that inactivates the active metabolites of estrogen, 2- and 4-hydroxyestradiol. Inhibition of inactivation should result in a secondary estrogenic response as a result of the prolongation of the action of endogenously formed estrogen. Thus, demonstration of the potent inhibition of estrogen metabolism by their catechol metabolites may explain the estrogenic effects reported for PCBs. - polychlorinated biphenyls (PCBs), kinetic models, phenolphthalein, dermal absorption, environmental estrogens, catechols
