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Listen to this siteWednesday 12 May 2004
This research project aims to develop new ways of detecting systemic responses and health effects from exposure to organophosphate pesticides.
Study Duration : March 2004 to September 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 development of markers to enable early and reliable detection of systemic responses and health effects arising from exposure to mixtures of pesticides (biomarkers of effect). Commissioned in response to this recommendation, project T10002 set out to develop novel effect biomarkers for organophosphate (OP) pesticide exposure.
Three related approaches were investigated, all based on the well-characterised mechanism of toxicity of OPs, inhibition of the enzyme acetylcholinesterase (AChE) through organophosphorylation of the serine residue at the enzyme's active site.
The first approach involved the development of antibodies recognising the OP-modified forms of the enzymes AChE and butyrylcholinesterase (pChE); the second attempted development of an immunoassay that could specifically detect the organophosphorylated active site of AChE and pChE; while the third was based on measurement of organophosphorylated residues of the amino acid serine. This approach was tried as the researchers hypothesised that modified serines may be excreted in the urine following turnover of organophosphorylated AChE and pChE.
Production of antibodies to OP-inhibited AChE and pChE proved difficult. While two antibodies were successfully produced and investigated in several immunoassay formats, all were less sensitive than the current method of monitoring OP exposure.
A sensitive method of detecting the OP-modified active site of pChE was successfully developed, but a potential problem with this approach is that the modified pChE rapidly converts to another, ‘aged’ form, which would not be detected. As the majority of pChE in a blood sample from an OP-exposed individual will be in the aged form, further development to enable detection of the aged enzyme is needed.
A number of antibodies were produced against OP-modified serines, and some proved useful in detecting OP-modified AChE and pChE at levels lower than current detection methods. However, it was not possible to produce an assay that could detect the OP-modification most likely to be found in blood after OP exposure.
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