Predictive toxicodynamics: Empirical/mechanistic approaches

Toxicology in Vitro : an International Journal Published in Association with BIBRA
J M Frazier

Abstract

A major objective of the toxicological sciences is to predict the in vivo toxicological consequences of human exposure to pure chemicals, complex mixtures and commercial formulations. Historically, the experimental approach to this goal has been to investigate toxicological processes in whole animal models and extrapolate the results obtained to predict human risk using various extrapolation procedures (high-dose/low-dose extrapolation, interspecies extrapolation and route-to-route extrapolation). Can in vitro methods be more widely employed in quantitative risk assessment? One major limitation to the broader application of in vitro toxicity testing methods is the lack of validated techniques for the extrapolation of in vitro-derived toxicodynamic data to the in vivo situation. The objective of this paper is to describe some approaches to the development of techniques to extrapolate in vitro toxicity testing data to predict in vivo toxicological responses. An empirical approach within the context of a mechanistic framework is explored. The basic hypothesis is that the in vivo response can be constructed from a cellular toxicity factor that accounts for the cellular response and a toxicodynamic factor that relates toxicological ...Continue Reading

References

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Sep 1, 1991·Risk Analysis : an Official Publication of the Society for Risk Analysis·C J Portier, A Kopp-Schneider
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Sep 15, 1982·Toxicology and Applied Pharmacology·R E DudleyC Klaassen
Aug 1, 1995·Toxicology in Vitro : an International Journal Published in Association with BIBRA·J M Frazier

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Citations

Feb 6, 2004·Toxicology in Vitro : an International Journal Published in Association with BIBRA·John M Frazier

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