Toxicokinetics of volatile organic compounds and metabolites kinetics
Hines, Carey C.
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Volatile Organic Chemicals (VOCs) represent a significant threat to the health of both humans and animals. Widespread use of volatile organic chemicals (VOCs) has resulted in their dissemination throughout the environment. Many people living in the U.S. are exposed daily to these chemicals, primarily via indoor air and drinking water. Home use of volatile organic chemical (VOC)-contaminated tap water commonly results in exposure by multiple routes. Previously, toxicity/carcinogenicity risk assessments focused primarily on the amount of chemical ingested in the water an individual consumed. It is now recognized that inhalation exposures during showering and other water-use activities can also contribute significantly to the total systemically absorbed dose. The goal of this research is to understand the pharmacokinetics and pharmacodynamics of DCE, TCE, TRI and their metabolites when exposure occurs via different routes, as well as to contribute to the development of a physiological based pharmacokinetic model for DCE, TCE, and TRI. Many of the previous toxicokinetic studies with volatile organic compounds have been done by inhalation exposure. This is due to the fact that this is the primary route of exposure, but also due to the expense and time associated with oral gavage and gastric infusion. Compounds entering the body through the lung are only affected by one elimination organ which is the lung before reaching systemic circulation, where as, when a compound is ingested it must pass through three elimination organs: Gut (efflux transporters), liver, and the lungs before reaching systemic circulation. The most important contribution of the findings in these studies are that they illustrate the importance of designing experimental protocols that are relevant to actual human exposures.