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T10011: Interindividuality in cytochrome P450 and paraoxonase mediated metabolism of mixtures of pesticides

Wednesday 6 July 2005

This research project will investigate the influence of genetic variability in enzyme activity on the toxicity of mixtures of pesticides.

Study Duration : March 2005 to February 2008

Contractor : CXR Biosciences

Background

In its report on Risk Assessment of Mixtures of Pesticides and Similar Substances, the Committee on Toxicity of Chemicals in Food Consumer Products and the Environment (COT) highlighted the need for characterisation of possible variability in human responses to mixtures of residues, including genetic susceptibility.

This project will adopt an enzymological approach to investigate the role of polymorphic drug metabolising enzymes in the toxicity of mixtures of pesticides.

Research Approach

The project will investigate the role of cytochromes P450 and paraoxonase in variability in response to individual pesticides and mixtures. Metabolism of selected pesticides will be characterised. In vitro techniques will be used to investigate interactions of the pesticides in mixtures at low individual concentrations in human tissues. The data obtained will provide a framework for future development of mathematical models to predict the effects of individual variability on the metabolism, and hence toxicity, of complex pesticide mixtures.

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