Physiological modeling human exposures to 1,3-butadiene: 1,3-butadiene (BD) is a colorless gas that is used as a raw material in the polymer industry. Inhalation exposures to BD have been demonstrated to be carcinogenic in rats and mice. Epidemiological studies have suggested that there exists an association between exposure to BD and leukemia. The current study focuses on quantifying the toxicokinetic behavior of BD in humans. Data are generated from a controlled-exposure human volunteer study, and used to examine several important topics related to physiologically based toxicokinetic (PBTK) modeling. The research techniques developed for BD can be used to study variable exposure patterns, other toxic materials, and toxicological interactions from exposures to chemical mixtures.
Analysis of aggregate exposure to methyl tertiary-butyl ether: Methyl tertiary-butyl ether is a volatile organic oxygenate that has been used as a fuel additive since the 1970s. Widespread contamination of groundwater and surface water has occurred from the storage of gasoline. The possible routes of exposure to MTBE are dermal contact, inhalation, and oral ingestion. A physiologically based toxicokinetic (PBTK) model is used to examine the kinetic behavior of MTBE and its metabolite tertiary-butyl alcohol (TBA) from aggregate exposures to MTBE in air and water. The model includes detailed mathematical descriptions of the skin and of the gastrointestinal tract. Future research will examine the relationship between exposure to MTBE and internal dose metrics for real-world exposure scenarios.
Toxicokinetic models of dermal exposure to jet fuel: Dermal exposure to Jet-Propulsion Fuel 8 (JP-8) is prevalent in the United States Air Force. Dermal exposure to JP-8 are poorly characterized and quantitative estimates of the contribution of dermal exposure to the internal dose of JP-8 are unknown. To fill this data and knowledge gap, a controlled dermal exposure study was designed to quantify the toxicokinetic behavior of naphthalene, 1-methyl naphthalene, 2-methyl naphthalene, decane, undecane, and dodecane. A physiologically-based toxicokinetic (PBTK) model of dermal and inhalation exposure to JP-8 was then developed and used to quantify the contribution of dermal exposure to the internal dose of naphthalene. Overall, this research has presented a new direction for toxicokinetic modeling human exposures to complex chemical mixtures. This modeling strategy may be used to better assess the risks associated with JP-8 exposures in human populations.