DOI

10.17077/etd.m2a3uliu

Document Type

Thesis

Date of Degree

Spring 2017

Access Restrictions

.

Degree Name

MS (Master of Science)

Degree In

Occupational and Environmental Health

First Advisor

Peter S. Thorne

First Committee Member

Hans-Joachim Lehmler

Second Committee Member

Michael Duffel

Abstract

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.

Public Abstract

Polychlorinated biphenyls (PCBs) are a group of 209 industrial chemicals that are found globally throughout the environment in air, water, and soil. Their previous use in building materials has contributed to the contamination of indoor air. This often overlooked issue is a concern for the health of school children because PCBs can enter the body via inhalation. PCB28 was found in the serum of over 20% of participants in the AESOP Study, which investigates PCB exposures among school children and their mothers. Little is known about the biological fate of PCBs after inhalation, which makes it difficult to assess risk.

In order to track the absorption, distribution, metabolism, and excretion of PCBs in the body, rats were exposed to radiolabeled PCB28 at two different doses. After lung exposure, 36 tissue types and digestive matter from five gastric compartments were removed and radioactivity was measured. For each tissue, the amount of radioactivity corresponded to the PCB concentration.

Data show that PCB28 is completely absorbed by the lung, quickly enters the blood stream, and is distributed to all tissues within minutes of exposure. These findings are comparable to PCB11, which our lab previously reported on. Unlike PCB11, PCB28 did not undergo extensive metabolism and little was excreted via urine and feces. As a result, the majority of PCB28 was retained in the body over the 244hr study period, primarily in skin and adipose tissue.

Keywords

Inhalation, PCB28, Polychlorinated biphenyls, Toxicokinetics

Pages

viii, 51 pages

Bibliography

Includes bibliographical references (pages 41-49).

Copyright

Copyright © 2017 Nicole Marie Brandon

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