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FOI release

FOI ATI1136 - DEFRA project VM02117 2001-2003

Published 5 February 2026

1. ATI1136 Request

  1. Please can you provide me with the follow up findings of DEFRA project VM02117 2001-2003 ‘Characterisation of non- acetylcholinesterase actions of OPs by identification of novel protein targets - VM02117’ ‘Contractor / Funded OrganisationsÌýMedical Research Council’, as shown in the final report, namely the OP targets identified and their and relevance to human health - ‘‘Further work Assuming that there are no further hold ups, in the next six months the OP targets in the brain will be identified by mass spectrometric analysis and then fully characterised and their relevance to human health ascertained.’Ìý

  2. In addition, please can youÌýadviseÌýwhat further work has been conducted in relation to this statement in the report and provide me with the findings of any further studies:Ìý

‘C´Ç²Ô³¦±ô³Ü²õ¾±´Ç²Ô²õÌý

This study has confirmed our original hypothesis: that there are previously unrecognised proteins present in the brain that are adducted by organophosphates to which humans are currently exposed at dose levels which are low enough not to induce warning cholinergic signs. Furthermore, we have shown that, of the six organophosphates tested, each adducts a different spectrum of target proteins. Just one of them (chlorpyrifos) reacted only with the conventional target, acetylcholinesterase. This variability across structures has one important consequence: if the non-cholinesterase mediated actions of organophosphates are mediated by these proteins, then organophosphates must be assessed on a compound-by-compound basis - not as a homogenous class.’

2. Our reply

Q1

The VM02117 study wasÌýinitiatedÌýwith VMD support for two years (2001–2003). After this funding concluded, the Medical Research Council providedÌýadditionalÌýsupport until 2006.

Key findings from this work were published in peer-reviewed journals:Ìý

  • Carter, W.G.,ÌýTarhoni, M., Rathbone, A.J., & Ray, D.E. (2007).ÌýDifferential protein adduction by seven organophosphorus pesticides in both brain and thymus.ÌýHuman & Experimental Toxicology, 26(4), 347–354.Ìý ÌýÌý

  • Tarhoni, M.H., Lister, T., Ray, D.E., & Carter, W.G. (2008).ÌýAlbumin binding as a potential biomarker of exposure to moderately low levels of organophosphorus pesticides.ÌýBiomarkers, 13(4), 343–363.Ìý

Q2

At the request of Ministers, the Committee on Toxicity (COT)ÌýestablishedÌýa Working Group to assess whether low-dose exposure to organophosphates (OPs) could lead to long-term health effects. The Group’s 1999 reportÌýidentifiedÌýseveral knowledge gaps. In response, a cross-Government initiative was launched under the Four Point Plan on Organophosphates to coordinate new research. The VMD-funded projectsÌýregardingÌýhuman health listed below were part of this plan and itsÌýsubsequentÌýactivities (in addition to VM02117 referenced in your question). Reports and findings are publicly available via the links provided:Ìý

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