The construction of a pharmacokinetic model for the disposition of polychlorinated biphenyls in the rat.
The construction of a preliminary pharmacokinetic model for the distribution, long-term storage sites, excretion, and metabolism of selected polychlorinated biphenyls (PCBs) in the rat is described. Following intravenous administration of radioactive PCBs, several metaboiltes of each PCB isomer were detected in urine or feces, excreted primarily as glucuronide conjugates. The relative and absolute amount of metabolites excreted depended upon the degree of chlorination and the position of the chlorine on the biphenyl molecule. Concerning long-term storage sties, an unanticipated finding was accumulation in skin, as revealed by the particularly long half-life of the 6-CB isomer in skin. A flow diagram of the model is presented, as are the differential equations, solved by computer for a given dose schedule, for the individual mass balances on parent and metabolite in each of the compartments that represent the organs or regions in which the concentration is assumed to be uniform. Low-level, long-term doses of PCBs produce a variety of toxicologic symptoms which appear only after long-time exposure. Such models should be useful in explaining and predicting the toxicities induced by exposure to PCBs and similar contaminants and the time required to reach a steady-state tissue concentration for given long-term doses.
D000818:Animals; D007700:Kinetics; D008954:Models, Biological; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D011078:Polychlorinated Biphenyls