Document Type

Dissertation

Date of Degree

Spring 2013

Degree Name

PhD (Doctor of Philosophy)

Degree In

Human Toxicology

First Advisor

Peter S. Thorne

Abstract

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.

Keywords

biological fate, health outcomes, inhalation exposure, PCB

Pages

xiii, 158 pages

Bibliography

Includes bibliographical references (pages 147-158).

Copyright

Copyright 2013 Xin Hu

Included in

Toxicology Commons

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