The overall objective of this study was to develop an in vitro based screening approach to determine the biotransformation rate constants of neutral hydrophobic organic chemicals in rats from rat liver S9 bioassays, and to test this screening approach by comparing in-vitro predicted biotransformation rates to in-vivo measured biotransformation rates. The test chemicals used for this study were pyrene, benzo(a)pyrene, hexachlorocyclohexane-beta, methoxychlor, mono-n-butyl phthalate, and 4-n-nonylphenol. In-vitro biotransformation rate constants were successfully obtained for all test chemicals and extrapolated to whole organism biotransformation rate constants using various IVIVE models. All the model outputs (IVIVE & QSAR) were compared to one another using descriptive statistical analysis. Various statistical parameters imply that all IVIVE models are very similar in performance. This indicates that the IVIVE-b model and IVIVE-Krause & Goss model (blood flow not considered), which require fewer biological parameters, could be used instead of the IVIVE-ph and IVIVE-Krause & Goss model (blood flow considered) for bioaccumulation assessment. Additionally, the IVIVE models were shown to perform slightly better than the QSAR models, indicating that the IVIVE models might be a better tool for estimating biotransformation rate constants compare the QSAR models. However, due to the variability in the in-vivo data and only a few chemicals being tested, a definitive conclusion cannot be made regarding which model performs the best. Furthermore, the IVIVE and QSAR models could be further upgraded in the future and only time will tell which models are the best for predicting whole organism biotransformation rate constants in rats.
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Thesis advisor: Gobas, Frank
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