摘要：Most of the available data on chemical interactions have been obtained in animal studies conducted by administering high doses of chemicals by routes and scenarios different from anticipated human exposures. A mechanistic approach potentially useful for conducting dose, scenario, species, and route extrapolations of toxic interactions is physiological modeling. This approach involves the development of mathematical descriptions of the interrelationships among the critical determinants of toxicokinetics and toxicodynamics. The mechanistic basis of the physiological modeling approach not only enables the species, dose, route, and scenario extrapolations of the occurrence of toxicokinetic interactions but also allows the extrapolation of the occurrence of interactions from binary to multichemical mixtures. Examples are presented to show the feasibility of predicting changes in toxicokinetics of the components of complex chemical mixtures based on the incorporation of binary interaction data within physiologically based models. Interactions-based mixture risk assessment can be performed by simulating the change in the tissue dose of the toxic moiety of each mixture component during combined exposures and calculating the risk associated with each tissue dose estimate using a tissue dose versus response curve for all components. The use of such a mechanistic approach should facilitate the evaluation of the magnitude and relevance of chemical interactions in assessing the risks of low-level human exposures to complex chemical mixtures. Full text Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References . 1377 1378 1379 1380 1381 1382 1383 1384
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