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 Organisations Medical 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.’ 

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

‘Conclusions 

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 was initiated with VMD support for two years (2001–2003). After this funding concluded, the Medical Research Council provided additional support until 2006.

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

• Carter, W.G., Tarhoni, M., Rathbone, A.J., & Ray, D.E. (2007). Differential protein adduction by seven organophosphorus pesticides in both brain and thymus. Human & Experimental Toxicology, 26(4), 347–354.  https://doi.org/10.1177/0960327107074617  

• Tarhoni, M.H., Lister, T., Ray, D.E., & Carter, W.G. (2008). Albumin binding as a potential biomarker of exposure to moderately low levels of organophosphorus pesticides. Biomarkers, 13(4), 343–363.  https://doi.org/10.1080/13547500801973563

Q2

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

• Investigation of possible autoimmune responses induced by organophosphate exposure - VM02116 

• Disabling neuropsychiatric disease in farmers exposed to organophosphates - VM02115 

• Prediction of susceptibility to long-term genotoxic effects of organophosphate pesticide exposure - VM02301 

• A case-control study of neuropsychological and psychiatric functioning in sheep farmers exposed to OP pesticides - VM02126 

• Effects of sheep dip pesticides on differentiating nerve cells: Identification of novel markers of toxicity - VM02300 

• A Case -Controlled Study of the Neuropsychological and Psychiatric Functioning in sheep farmers exposed to Organophosphate Pesticides-Phase II of VM02126 - VM02302