Journal of Exposure Analysis and Environmental Epidemiology, RECONSTRUCTION OF SHORT-TERM MULTI-ROUTE EXPOSURE TO VOLATILE ORGANIC COMPOUNDS USING PHYSIOLOGICALLY BASED PHARMACOKINETIC MODELS PANOS G. GEORGOPOULOS, AMIT ROY, AND MICHAEL A. GALLO Environmental and Occupational Health Sciences Institute ABSTRACT An approach has been developed for implementing physiologically based pharmacokinetic (PBPK) models in an "inverse" mode to reconstruct short-term exposure concentrations and internal dose for multiroute and multimedia exposures to toxic volatile organic compounds. It has been applied to chloroform inhalation and dermal absorption. This modeling approach estimates exposure concentrations in different media through statistical optimization methods for the solutions of the PBPK models, such as likelihood maximization. The necessary input is a suitable physiological response metric, such as the time profile of concentration levels of toxicants or their metabolites in body fluids. Two PBPK models of different sophistication - the DP-PBPKM, which employs a partial differential equation description of dermal transport (i.e. based on Fick's second law for diffusive transport), and LP2S-PBPKM, which uses an ordinary differential equation description of transport (i.e. based on Fick's first law, which assumes steady state for mass fluxes) - have been utilized in this study. The model performance was evaluated using available ambient and exhaled breath chloroform concentration data from previously conducted shower and swimming pool studies, corresponding to inhalation only, and combined inhalation and dermal exposures. The exposure/dose reconstruction results were in agreement with observations when critical data, such as the peak exhaled concentration and the shape of the immediate post-exposure exhaled concentration profile, were available. Please contact us for a complete reprint of this article. |