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Listen to this siteThursday 18 May 2006
This research project aims to investigate the nature of the effects of combined exposure to pesticides on the major detoxification pathway.
Study Duration : April 2006 to November 2006
Contractor : Health and Safety Laboratory
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 and characterisation of the nature of combined actions of chemical mixtures. This project focuses on possible combined actions of organophosphates, carbamates and pyrethroids on the rate of metabolic detoxification via hydrolysis.
These three classes of pesticides - organophosphates, carbamates and pyrethroids - comprise the major agricultural insecticides in current use. Chemically, they share a common structural feature; they all contain an ester linkage. Hydrolysis of this bond is considered to be an important detoxification pathway for each of these classes of pesticide. Recent evidence has suggested that pyrethroid hydrolysis can be inhibited by low, dietary relevant, concentrations of organophosphate. Whether similar interactions may occur for carbamates is unknown. This work will employ human tissues and in vitro techniques to investigate whether dietary exposure to mixtures of organophosphates, carbamates and pyrethroids might be expected to alter the metabolic profile that would be expected from exposure to single compounds.
Using human liver microsome and cytosol fractions, hydrolysis of the ester bond was confirmed to be the major route for detoxification of pyrethroid pesticides and the ‘oxon’ metabolites of organophosphates. Surprisingly, however, no significant hydrolysis of carbaryl, a carbamate pesticide, was determined.
When tested in combination, carbaryl or the oxon metabolites of organophosphates inhibited hydrolysis of the pyrethroids. The potency of this inhibition was greatest for chlorpyrifos-oxon, approximately 50 times less for malaoxon and 100-1000 times less for carbaryl. The level of inhibition of hydrolysis observed varied for the different pyrethroids, which may indicate that different esterases are involved in their metabolism. Pyrethroids themselves did not affect each others’ metabolism.
These results indicate that organophosphate and carbamate pesticides have the potential to affect the metabolism of pyrethroids. However, these studies were performed at relatively high doses and it is not clear whether these effects would occur at the in vivo concentrations of these pesticides arising from dietary intake. Given that no interactions were observed with mixtures of pyrethroids, it is unlikely that dietary exposure to mixtures of these compounds will influence their rates of detoxification.
The final report is available from the Agency’s Information Centre.
To obtain a copy, please contact the Enquiry Desk, Information Services, Food Standards Agency (tel: 020 7276 8181/8182 or email:
infocentre@foodstandards.gsi.gov.uk
)
For any enquiries concerning this research project, please contact the relevant Programme contact or email: science@foodstandards.gsi.gov.uk
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