Distribution, elimination and toxicity assessment of semi-volatile polychlorobiphenyls after inhalation exposure.

摘要

Inhalation exposure to semi-volatile polychlorobiphenyls (PCBs) that ubiquitously exist in the environment has the potential to cause adverse health effects. Recently identified sources of airborne PCBs, especially non-legacy sources, stress the importance of risk assessment for inhalation exposure. However, the fate of inhaled airborne PCBs in biological systems and the resultant toxicity remain unexplored.;The objective of this thesis research was to investigate the distribution and elimination of semi-volatile PCBs in biological systems after inhalation exposure and evaluate the biologic and toxicologic consequences. This objective was achieved by conducting the following inhalation studies in rats: a short-term exposure study of the body burden and elimination; a subchronic exposure toxicity study; an acute exposure study of PCB11 metabolism; and a mass balance study of [14C]PCB11 following lung exposure.;PCBs found in technical Aroclor mixtures and PCB11 were readily absorbed and distributed following nose-only inhalation exposure. PCBs accumulated in adipose tissue, but decayed in other tissues with biological half-lives of several hours. Their elimination was dependent on the structure of the PCB congeners and the metabolic nature of the organ. Lower-chlorinated PCBs exhibited more rapid clearance than higher-chlorinated congeners yet differential rates of elimination were also seen within the homologue. A distinct congener pattern was found in tissues, ranging from tri- to pentachorobiphenyls after subacute and subchronic exposure.;Rapid elimination of PCB11 and its metabolite, 4-OH-CB11, were detected in liver following nose-only inhalation exposure by our established methodology. Further investigation revealed that [14C]PCB11 was 99.8% absorbed in lung. Elimination of the [14C]PCB11 and products consisted of an initial fast phase followed by a slow clearance phase. [14C]PCB11 underwent rapid and extensive metabolism in liver. The major products were phase II metabolites which dominated in the non-adipose tissues and were eliminated via the large intestine and urine.;Overall, differential congener elimination was found after inhalation of airborne PCBs, with minimal toxicity. Lower-chlorinated congeners were rapidly and extensively metabolized to phase II products and eliminated within hours.