Dissertation
Comprehensive toxicity assessment of inhalation exposure to polychlorinated biphenyls
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2021
DOI: 10.17077/etd.005909
Abstract
Few in vivo inhalation studies have explored the toxicity of environmentally-relevant mixtures of polychlorinated biphenyls (PCBs). The manufacture of industrial PCBs was banned in the U.S. in 1978, but production continues as byproducts in building materials. Schools represent a significant source of airborne exposures to both legacy and non-legacy PCBs, placing children at particular risk. We hypothesize that inhalation exposure to airborne PCB mixtures could lead to multi-system toxicity, including neurological, immune, endocrine, reproductive, and hematopoietic systems. To evaluate the impact of these exposures, we generated an airborne mixture of PCBs, called the School Air Mixture (SAM), designed to match the profile of an older school from our adolescent cohort study (the AESOP Study). We conducted the study to address three specific aims: using in vivo inhalation exposure to assess the toxicity in three different exposures: subchronic, chronic, and perinatal exposures. Female Sprague-Dawley rats were exposed either to SAM or filtered air (sham) in nose-only exposure systems. Congener-specific air and tissue PCB profiles were assessed using gas chromatography-tandem mass spectrometry for 209 congeners. A wide array of adverse health outcomes were evaluated including general health status (weight gain, body condition), organ histopathology, cytotoxicity, inflammation, immunotoxicity, oxidative stress, antioxidant status, thyroid hormone and reproductive hormone dysregulations, genotoxicity, developmental toxicity, neurobehavioral changes and neurotoxicity.The subchronic study demonstrated a modest effect on spatial learning and memory in SAM-exposed rats. PCB exposure induced oxidative stress in liver and lung, affected the maturational stages of hematopoietic stem cells, reduced telomerase activity in bone marrow cells, and altered the gut microbiota. In the chronic exposure, we observed that PCB exposure impaired memory; induced anxiety-like behavior; significantly reduced white blood cell counts; mildly disrupted metabolomics in plasma; and influenced transcription processes in brain with 274 up-regulated and 58 down-regulated genes. Despite relatively high exposure and tissue loading, minimal toxicity was seen in the rats, suggesting that this inhalation exposure is close to the lowest observed adverse effect level. The perinatal exposure to a lower chlorinated PCB mixture resulted in significantly reduced fetal weight and higher postnatal mortality in female pups. Endocrine system, especially thyroid hormones and estradiol, as well as cytokines and chemokines expression in serum, were disrupted in a sex-dependent manner. Neurobehavioral testing demonstrated more impaired memory in male than female pups, hyperactivity and reduced anxiety-like behavior only in male pups.
This dissertation investigated for the first time, the toxicity of environmentally-relevant PCB mixture in a comprehensive manner from short-term to long-term and finally perinatal exposures. We could provide insight into the overall risk assessment of airborne PCBs and extrapolate the risk to human.
Details
- Title: Subtitle
- Comprehensive toxicity assessment of inhalation exposure to polychlorinated biphenyls
- Creators
- Hui Wang
- Contributors
- Peter S Thorne (Advisor)Hans-Joachim Lehmler (Committee Member)Gabriele Ludewig (Committee Member)Kai Wang (Committee Member)Jonathan A Doorn (Committee Member)
- Resource Type
- Dissertation
- Degree Awarded
- Doctor of Philosophy (PhD), University of Iowa
- Degree in
- Occupational and Environmental Health
- Date degree season
- Summer 2021
- DOI
- 10.17077/etd.005909
- Publisher
- University of Iowa
- Number of pages
- xiv, 121 pages
- Copyright
- Copyright 2021 Hui Wang
- Language
- English
- Description illustrations
- color illustrations
- Description bibliographic
- Includes bibliographical references (pages 110-121).
- Public Abstract (ETD)
Polychlorinated biphenyls (PCBs) are environmental pollutants and are still persistent in our environment, especially indoor, although the production was banned many decades ago. PCBs have been shown to cause multiple health problems to human, including cancer, immune, reproductive, endocrine, and neurological systems problems, etc. Older schools built with PCB-containing materials were detected with significant levels of PCBs in indoor air, which placed children at particular risk. Recently, another alarm was rung by the finding of emerging source of PCBs in paint pigment.
For the general population, PCBs were exposed primarily by ingestion and inhalation. As the levels of PCB have been declining over the years, inhalation is becoming a major route for PCBs exposure. It is critical to understand the impacts of inhaling the toxic PCBs as related studies were scarce.
My thesis focused on investigating the toxicological effects of inhaling PCBs using an animal model, namely female rats. We conducted the studies in three different contexts: short-term (28 days), long-term (13 weeks), and during pregnancy. Rats were exposed to lab-generated PCB mixtures via inhalation. After that we necropsied rats to evaluate the toxicity. With these three aspects, we can uncover the health effects of inhalation of PCBs on adults and newborn rats. However, we need to explain the importance of these findings to human health. With my thesis, we could provide valuable information to government, such as the Environmental Protection Agency (EPA) for setting up an acceptable level of PCBs.
- Academic Unit
- Occupational and Environmental Health
- Record Identifier
- 9984124571602771
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