Food Standards Agency
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Listen to this siteTuesday 15 August 2006
This research project aims to identify groups of pyrethrins and pyrethroids sharing a common toxic effect by a common mechanism of action.
Study Duration : June 2006 to May 2009
Contractor : Imperial College London
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 that groups of pesticides having common targets of toxicological action should be identified. The Science Group of the Food Standards Agency has prioritised five classes of pesticides/veterinary medicines to be assessed for common mechanism grouping including pyrethroids and natural pyrethrins.
Pyrethrins and pyrethroids are acutely neurotoxic by interacting with Na + channels. Other cellular targets, such as voltage-activated Ca 2+ channels, may also be affected. Hence, to define common mechanism groups (CMGs) it is proposed to use intracellular protein profiles, determined by techniques such as SELDI-TOF mass spectrometry, in neuronally-derived cells such as SH-SY5Y. Effects on functional endpoints, such as neurotransmitter transport, will also be assessed. Proteins with changes suggestive of a CMG (e.g. common to structural analogues), will be identified by multidimensional protein identification technology and assessed for biological relevance from the pathway involved.
The role of selected proteins in the functional responses of cells will be confirmed by blocking expression using small interference RNA species. The ultimate aim of the project is to identify a small number of functionally important proteins characteristic of each CMG, the number of protein profiles determining the number of CMGs.
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