Date of Degree
Access restricted until 07/13/2018
MS (Master of Science)
Occupational and Environmental Health
Peter S. Thorne
Although the production of polychlorinated biphenyl (PCB) technical mixtures has been banned in the U.S. since the 70’s, they remain ubiquitous in the environment, particularly in indoor and ambient air. Due to the presence of PCB’s in air, inhalation is a significant route of exposure. PCBs released from various building materials have been shown to contaminate the indoor air in homes and schools. In the AESOP Study, an epidemiologic study of PCB exposures among school children and their mothers, PCB28 was found in the serum of over 20% of participants. Data are lacking on the absorption, distribution, metabolism, and excretion (ADME) of inhaled PCBs and on the biological fate and dose-specific toxicological endpoints.
In order to inform toxicokinetic modeling for risk-assessment, we are conducting ADME toxicological studies with lung exposure to a representative trichlorobiphenyl, and evaluating the uptake from the lung and the distribution, metabolism, and excretion. Male Sprague-Dawley rats were exposed to [14C]PCB28 via intratracheal instillation at two different doses (42 µg/rat and 4.2 µg/rat). Digestive matter from five separate compartments of the gastrointestinal tract and thirty-six tissue types were excised and measured by scintillation counting. Exhaled air and excreta were also collected and analyzed. Measurements for the high dose were made at 12, 25, 50, 100, 200, 400, 720, and 1440 min, and for the low dose at 2, 12, 50, 200, and 720 min post-exposure.
Data show that pulmonary uptake exceeded 99% in both doses. [14C]PCB28 entered the blood stream and distributed quickly to all tissues within minutes of dosing. In the high dose, the majority of radioactivity initially went to the muscle and liver, while in the low dose [14C]PCB28 initially distributed to the muscle, esophagus, and trachea, before being redistributed to the skin and adipose tissue, where it accumulated in both doses. In most tissues, elimination was biphasic, consisting of an initial fast phase with a half-life (t1/2) of 7-93 min (high dose) and t1/2 of 6-60 min (low dose), followed by a slower phase with t1/2 of 5-18 hours (high dose) and t1/2 of 3-18 hours (low dose). The metabolism of PCB28 was not extensive, with the parent compound as the major component in liver, kidney, serum, and adipose tissue. Excretion via urine and feces was limited, with 92% (high dose) and 88% (low dose) of radioactivity remaining in the tissues by the end of the time course, primarily in skin and adipose tissue.
Low urinary concentration relative to serum, suggested that parent PCB28 in serum would serve as an accurate biomarker for assessment of exposure to inhaled trichlorobiphenyls. The time course and tissue distribution is comparable to [14C]PCB11, while metabolism and excretion of [14C]PCB28 is much less extensive.
Inhalation, PCB28, Polychlorinated biphenyls, Toxicokinetics
viii, 51 pages
Includes bibliographical references (pages 41-49).
Copyright © 2017 Nicole Marie Brandon
Available for download on Friday, July 13, 2018