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T10016: Characterisation of the nature of combined actions of chemical mixtures and estimation of dose response relationships for pesticide mixtures

Thursday 10 August 2006

This research project aims to characterise potential interactions of mixtures of anti-acetylcholinesterase pesticides.

Study Duration : July 2006 to June 2008

Contractor : Central Science Laboratory

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) recommended a need for investigation of the nature and dose-response relationships for combined actions of pesticides. This project is designed to answer the specific question of whether anti-acetylcholinesterase pesticides are simply additive in their effect at different doses or if there is a more complex interaction (synergism or antagonism).

Research Approach

Experimental work will be carried out in vitro using the human neuroblastoma cell line SH-SY5Y. Cells will be exposed to different concentrations (doses) of single compounds, an equimolar ratio cocktail and a cocktail containing relative concentrations that are proportional to those likely to arise from dietary exposure.

The toxicity of the pesticides (two organophosphates and two carbamates) will be measured as inhibition of acetylcholinesterase activity. Appropriate statistical methods will be used to test a null hypothesis that the exposure-response relationship for mixtures along each fixed-ratio ray is the same as that predicted by combining (adding) the effects of the individual chemicals.

The outcome from this project will not only provide an answer to the direct question of interaction between four anti-cholinesterase pesticides, but also provide a model for future study of more complex food contaminant cocktails.

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