T10015: Functional impact of polymorphisms of transport proteins upon pesticide delivery to the CNS

Monday 14 August 2006

This research project aims to investigate the effect of individual genetic responses to pesticides.

Study Duration : April 2006 to March 2008

Contractor : Newcastle University

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 is designed to test whether genetic variability in sensitivity to neurotoxicity from pesticides may be due to variability in the delivery of toxins to the central nervous system (CNS) and variability in their distribution within the CNS.

Research Approach

To test this hypothesis, the specific aims of the project are to:

Identify the importance of members of SLC0 SLC6, SLC22 and ABC1 families of organic solute transporters in the delivery of selected pesticides to the CNS.
Define the impact of high frequency single nucleotide polymorphisms (SNPs) of key transporters upon delivery of selected pesticides to the CNS.
Assess the impact of SNPs upon measures of neurotoxicity in target neuronal cells.

The outcome of this work will be a comprehensive understanding of the transport processes involved in the delivery of pesticides to the CNS, together with an explanation of the impact of SNPs of transporters upon CNS exposure to toxic substances and an understanding of the interactions between pesticides at the level in transporters that may modulate CNS exposure.

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T10015: Functional impact of polymorphisms of transport proteins upon pesticide delivery to the CNS

Background

Research Approach

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