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Evaluating Pharmacokinetic and Pharmacodynamic Interactions with Computational Models in Cumulative Risk Assessment
Citation:
TAN, YU-MEI, M. E. ANDERSEN, J. L. CAMPBELL, AND H. J. CLEWELL. Evaluating Pharmacokinetic and Pharmacodynamic Interactions with Computational Models in Cumulative Risk Assessment. International Journal of Environmental Research and Public Health. Molecular Diversity Preservation International, Basel, Switzerland, 8(5):1613-1630, (2011).
Impact/Purpose:
The National Exposure Research Laboratory′s (NERL) Human Exposure and Atmospheric Sciences Division (HEASD) conducts research in support of EPA′s mission to protect human health and the environment. HEASD′s research program supports Goal 1 (Clean Air) and Goal 4 (Healthy People) of EPA′s strategic plan. More specifically, our division conducts research to characterize the movement of pollutants from the source to contact with humans. Our multidisciplinary research program produces Methods, Measurements, and Models to identify relationships between and characterize processes that link source emissions, environmental concentrations, human exposures, and target-tissue dose. The impact of these tools is improved regulatory programs and policies for EPA.
Description:
Simultaneous or sequential exposure to multiple chemicals may cause interactions in the pharmacokinetics (PK) and/or pharmacodynamics (PD) of the individual chemicals. Such interactions can cause modification of the internal or target dose/response of one chemical in the mixture by other chemical(s), resulting in a change in the toxicity from that predicted from the summation of the effects of the single chemicals using dose additivity. In such cases, conducting quantitative cumulative risk assessment for chemicals present as a mixture is difficult. The uncertainties that arise from PK interactions can be addressed by developing physiologically based pharmacokinetic (PBPK) models to describe the disposition of chemical mixtures. Further, PK models can be developed to describe mechanisms of action and tissue responses. In this article, PBPK/PD modeling efforts conducted to investigate chemical interactions at the PK and PD levels are reviewed to demonstrate the use of this predictive modeling framework in assessing health risks associated with exposures to complex chemical mixtures.
URLs/Downloads:
Evaluating Pharmacokinetic and Pharmacodynamic Interactions with Computational Models in Cumulative Risk Assessment (PDF, NA pp, 219 KB, about PDF)International Journal of Environmental Research & Public Health
