Graduate Thesis Or Dissertation
 

Assessing Exposures and Simplifying Complex Mixtures of SVOCs for Hazard Characterization using Alternative Model Systems

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https://ir.library.oregonstate.edu/concern/graduate_thesis_or_dissertations/cv43p458m

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  • Throughout their lifetime individuals are exposed to complex mixtures of chemicals. The study of chemical mixtures is an internationally recognized research priority, but seemingly complex challenge. To reduce the intricacy of studying mixtures, researchers have identified different prioritization methods based on exposure or the toxicity of chemicals. However, understanding the prevalence and concentration of chemicals in the environment as well as their biological impacts is essential for assessing risk of a given chemical or chemical mixture. Throughout this dissertation, tools used for exposure science and toxicology were utilized to further understand chemical exposures and prioritize chemicals for hazard characterization. In Chapter 2 fourteen chemicals identified in over 50% of personal samplers (G14) analyzed from a representative population, from fourteen different communities spanning three different continents, was utilized for toxicological investigations. This study describes a novel approach to prioritize and broadly evaluate the hazards of a representative mixture by coupling data from personal sampling devices with high-throughput bioactivity screenings using in vitro and non-mammalian in vivo models. To account for species and sensitivity differences, screening was conducted using primary normal human bronchial epithelial (NHBE) cells and early life-stage zebrafish. Chemical bioactivity was dependent on the model system, with five and eleven chemicals deemed bioactive in NHBE and zebrafish, respectively. Mixtures of the G14 and most potent G14 chemicals were created to assess potential mixture effects. In both NHBE and zebrafish, mixture effects were observed when screening mixtures of the most potent chemicals. Observations of BMC-based mixtures in NHBE (NHBE BMC Mix) and zebrafish (ZF BMC Mix) suggested antagonistic effects. In this study, consumer product-related chemicals were prioritized for bioactivity screening using personal exposure data. High-throughput high-content screening was utilized to assess the chemical bioactivity and mixture effects of the most potent chemicals. In Chapter 3 several approaches were explored to form sufficiently similar mixtures of polycyclic aromatic hydrocarbons (PAHs). There is a growing need to establish alternative approaches for mixture safety assessment of PAHs. Due to limitations with approaches, a promising alternative is to use sufficiently similar mixtures. However, there is a lack of an established framework to form sufficiently similar mixtures. Multiple data streams including environmental concentrations and empirically and QSAR derived toxicity data for cancer and non-cancer endpoints were used to prioritize components for mixture formations. Passive air samplers were deployed at a legacy creosote site impacted by wildfire smoke. A mixture of 30 parent and alkylated PAHS identified in samples was created (CF Mix). Mixtures of the CF mix were formed based on relative abundance (Abun Mix), average toxicity values (Tox Mix), and a weighted approach incorporating toxicity and abundance (Weighted-Tox Mix). Hazard characterization of these mixtures was performed using high-throughput screening in NHBE and zebrafish. Differences in chemical composition and potency were observed based on selected approach, with Tox Mix being the most potent mixture in both models. In NHBE Weighted- Tox Mix was the second most potent followed by Abun Mix and CF Mix. The Weighted-Tox Mix approach was determined to be the ideal approach due its ability to prioritize chemicals with high exposure and hazard potential. Results from this study will provide a workflow for prioritizing components to create sufficiently similar mixtures for hazard characterization. Toxicity information for less widely studied mixtures of PAHs was also identified and warrant further investigation into their specific mechanisms and chemical interactions. In Chapter 4 paired indoor and outdoor passive samplers were deployed at twenty-four locations across the United States using a community engaged approach. Samples were analyzed for over 1500 SVOCs to identify common patterns in exposure profiles representative of indoor and outdoor air quality. Although less widely studied, indoor air pollutants can be anywhere from two to five times higher than outdoors. Impacts of household behavior and environmental and demographic factors on exposure profiles were also investigated. Unique differences between indoor and outdoor profiles were found, with indoor having higher concentrations and more detections of SVOCs than outdoor. A significant relationship between household use of air fresheners and candles/incense and an increase in detection and concentrations of fragrance chemicals was discovered. Associations between carpet use and SVOC detection frequency and concentrations was also observed. These associations were chemical dependent with some showing a positive association and others having a negative association with carpet use. Environmental and demographic factors also had an impact on indoor and outdoor profiles and were chemical dependent. Results from this study provide valuable information regarding indoor and outdoor chemical profiles and factors that impact the composition and concentrations of these chemicals. These findings can also help inform ways to reduce chemical exposure, by identifying certain consumer behaviors that may affect exposure profiles.
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  • Research reported in this publication was supported by the National Institutes of Environmental Health Sciences of the NIH under Award Numbers T32 ES 7060-39; P42 ES016465, P30 ES030287. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
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