Professor Smith's primary research interests are the characterization of environmental exposures for studies of health effects, and investigation of the quantitative relationship between environmental exposure and internal dose. He has developed a toxicokinetic modeling approach for designing exposure evaluations for epidemiological studies in collaboration with Dr. David Kriebel, UMass/Lowell. This approach uses clinical and other observational data to structure temporal models of apparent disease processes. The models can be used to design studies to explore the implications of mechanistic hypotheses about how toxic materials cause health effects.
Dr. Smith is currently using this approach to conduct the exposure assessment for a large cohort study of the US trucking industry with Dr. Eric Garshick of the VA Hospital System and Harvard Medical School. This study is investigating lung cancer mortality among workers who are exposed to diesel and other vehicle exhaust. This study will determine if there is a distinct risk from diesel engine emissions, as opposed to general combustion emissions from all sources, such as trucks, automobiles and home heating. Carbon nano and ultrafine particles with adsorbed polycyclic aromatic hydrocarbons (PAH) are one of the suspected set of agents. New approaches are being used to estimate current and historical exposures to these agents, including the use of economic data to model past air pollution levels.
Dr. Smith also has been conducting laboratory exposure study of human metabolism of 1,3-butadiene (BD), which is enzymatically activated to epoxides. BD is a very common urban air toxic pollutant which causes cancers in rats and mice, and is a probable human carcinogen. In his lab, uptake and washout of very small amounts of inhaled BD are observed for each volunteer using an approved human subjects protocol. These data are fitted with a toxicokinetic model to estimate the rate of metabolism. Dr. Smith hopes to assess BD's toxicokinetic behavior and ultimately to project human risk. The research apparatus and techniques developed for BD will also be applicable to study other toxic materials, which is a goal for future studies.
Working Group for Toxicokinetic and Disease Process Modeling - Dr. Smith is leading a small group of faculty, students, and post-doctoral fellows who wish to explore the use of models to investigate adverse human effects from environmental and occupational toxic exposures. Contact: tsmith@hohp.harvard.edu for further information.