Development and application of a generalized physiologically based pharmacokinetic model for multiple environmental...

The pharmacological disposition of four environmental contaminants resulting from acute and chronic exposure regimes is simulated using a general physiologically based pharmacological (PBPK) model. The model, which is detailed in supporting materials, is mechanistic in structure and relies on available physical-chemical partitioning and reactivity data, but experimental partitioning and absorption efficiency data can be used to refine the parameters. It is designed to complement environmental fate models, thus linking chemical emission rates with environmental and physiological behavior as part of the larger environmental risk assessment process. The model is illustratively applied to inhaled styrene and trichloroethene as well as ingested dibutyl phthalate and di(2-ethylhexyl) phthalate. The phthalate simulations include the corresponding monoester and conjugated monoester as metabolites. Tissue concentrations for each of the chemicals and metabolites are simulated for acute, occupational, and environmental exposure regimes. The same model is used for all chemicals and exposure regimes with only the physical-chemical properties, reaction rates, and exposure estimates being changed.