Neurotoxic Effects of Low-level Organophosphate Exposure in C. elegans and UK Agricultural Workers

Dawson, Alexander Steven (2023). Neurotoxic Effects of Low-level Organophosphate Exposure in C. elegans and UK Agricultural Workers. PhD thesis The Open University.



Exposure to organophosphate (OPs), pesticides, has been associated with poor mental health among agricultural workers. Although the impacts of acute exposure, such as poisoning due to AChE inhibition and cholinergic hyperexcitation, are well known, the mechanisms by which low-level exposure may impact mental health are not fully understood. Such investigations are complicated by confounding variables like physical health, life stress, and lifestyle factors.

This thesis sought to bridge this gap using an interdisciplinary approach, focusing on both the biological effects of low-level OP exposure, and its impact on human wellbeing. A model was developed using the invertebrate C. elegans to examine effects at a molecular level. Results demonstrated that exposure below the threshold for significant AChE inhibition led to behavioural changes in C. elegans linked to ACE-2 acetylcholinesterase and GAR-3 muscarinic receptor, suggesting that the cholinergic system mediates some effects of low-level OP exposure, even at very low-levels.

In addition, a survey among UK agricultural workers was conducted to understand the factors affecting mental health in OP-exposed populations. Data suggested that although depression symptoms were higher among agricultural workers compared to a control group of construction workers, lifestyle factors and stress appeared to be more important contributors to poor mental health than pesticide exposure.

In conclusion, the research provides evidence for potential neurotoxic effects of low-level OP exposure from the C. elegans model. However, its implication in human mental health is more nuanced, with stress and lifestyle factors playing significant roles, highlighting the complexity of real-world interactions between chemical exposure and human health.

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