Metabolic activation of chemicals: in-silico simulation†

† Presented at CMTPI 2005: Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (Shanghai, China, October 29–November 1, 2005).

Abstract

The role of metabolism in prioritising chemicals according to their potential adverse health effects is extremely important given the fact that innocuous parents can be transformed into toxic metabolites. Our recent efforts in simulating metabolic activation of chemicals are reviewed in this work. The application of metabolic simulators to predict biodegradation (microbial degradation pathways), bioaccumulation (fish liver metabolism), skin sensitisation (skin metabolism), mutagenicity (rat liver S-9 metabolism) are discussed. The ability of OASIS approach to predict metabolism (toxicokinetics) and toxicity (toxicodynamics) of chemicals resulting from their metabolic activation in a single modelling platform is an important advantage of the method. It allows prioritisation of chemicals due to predicted toxicity of their metabolites.

† Presented at CMTPI 2005: Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (Shanghai, China, October 29–November 1, 2005).

Keywords:

• Metabolic activation
• Biodegradation
• Bioaccumulation
• Mutagenicity
• Skin sensitisation

Acknowledgments

Research associated with this article was funded in part through an EPA cooperative research agreement (CR 83199501-0), as well as Research agreements with ExonMobil and Unilever. Gratitude is expressed to Drs. Jack Jones, Patricia Schmieder and Rick Kolanczyk (from US EPA) for the discussions improving the quality of the article.

Notes

† Presented at CMTPI 2005: Computational Methods in Toxicology and Pharmacology Integrating Internet Resources (Shanghai, China, October 29–November 1, 2005).