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A study published in Occupational & Environmental Medicine looks at occupational exposure to pesticides and Motor Neurone Disease (MND) risk.
Martin Scholze, Biomathematician & Biostatistician, Research Fellow at Brunel University of London, said:
“This is a well-conducted systematic review and meta-analysis that follows established methodological standards, including a pre-registered protocol, a comprehensive literature search, formal risk-of-bias assessment and appropriate sensitivity analyses. The review itself is rigorous, and the authors present their findings appropriately and cautiously. However, the strength of the conclusions is ultimately constrained by the quality and quantity of the available primary evidence on which the meta-analysis is based.
“The main finding, that occupational pesticide exposure is associated with an approximately 60% increased risk of ALS, is based on a relatively small number of predominantly retrospective case-control studies, with the principal pooled estimate relying on just six studies. Consequently, the evidence should be regarded as suggestive rather than definitive. The observed association is consistent with previous reviews, but it does not establish a causal relationship.
“A major limitation is exposure assessment. Most studies relied on self-reported occupational exposure, usually classified simply as “ever exposed”, without quantitative information on exposure intensity, cumulative dose or the specific active substances involved. Such exposure assessment is susceptible to recall bias and exposure misclassification, both of which may influence the estimated associations. Furthermore, the analysis combines many different pesticide classes and hundreds of chemically diverse active ingredients, preventing any conclusions regarding which pesticides, if any, are driving the observed association.
“Residual confounding also remains an important limitation. Although most studies adjusted for basic factors such as age, sex and smoking, agricultural workers are simultaneously exposed to numerous other occupational hazards, including solvents, fuels, metals, dusts and other chemicals, which were not consistently measured or controlled across studies. Differences in farming practices, lifestyle and socioeconomic factors may also contribute to the observed associations. These potential confounders do not invalidate the findings but reduce confidence that the observed association can be attributed solely to pesticide exposure.
“Another important consideration is that the included studies span several countries and more than three decades. During this period, pesticide regulations, approved active substances, application technologies, personal protective equipment requirements and worker training have changed substantially. Consequently, “occupational pesticide exposure” represents highly heterogeneous exposure scenarios, many of which may not reflect current agricultural practice or regulatory standards. The findings therefore should not be interpreted as implying that all pesticides currently in use carry a similar risk.
“Overall, the authors’ conclusions are appropriately cautious and are supported by the available data, provided they are interpreted as evidence of an association rather than proof of causation. The study strengthens the existing body of epidemiological evidence but also highlights the need for large prospective studies with quantitative exposure assessment, better characterisation of individual pesticides, and more comprehensive control of occupational and environmental confounding before stronger causal inferences can be made.”
Dr Wayne Grant Carter, Associate Professor, Course Director for the Medical Physiology and Therapeutics (MPT) degree, University of Nottingham, said:
“This is an interesting and timely review that collates studies considering the association between the relative risk of diagnosis of amyotrophic lateral sclerosis (ALS) and occupational pesticide exposure. The strength of the study lies in its use of a meta-analysis that considers the combined weight of relevant studies published in this field between 1990 and 2025. The conclusion from the study is that there is an increased risk of ALS with occupational pesticide exposure and that the risk correlates with the level of exposure; more risk for relatively high exposures. A limitation of the analysis is that it relates to pesticide classes (herbicides, insecticides, fungicides, etc.) rather than individual pesticides (or combinations thereof), but it suitably highlights the need to reduce pesticide exposure during occupational pesticide use.”
Prof Michael Swash, Emeritus Professor of Neurology, Barts and the London School of Medicine, QMUL UKHon Consultant Neurologist, said:
“1: The paper is carefully written and utilises advanced statistical methods applicable to environmental association work (not all of which are familiar to me).
2: The authors – mostly – are careful not to overstate their case, but from time to time they express conclusions which extend beyond the validity of their data. Their conclusion depends on a review of ALS cases culled from really very few published reports. No new data is presented. No attempt is made to consider the validity of these published reports, aside from reliance on the notion that the accuracy of diagnosis of ALS was reliable and consistent across the reports cited. This is perhaps unlikely? The use of the Belsh paper for diagnosis does not inspire confidence, since this is not ordinarily used in practice.
3: There is therefore the familiar possibility of errors carried over from these published reports– undetectable but likely to be very significant.
4: The authors seem to suggest that ALS is different from MND as a diagnosis – the two are in fact identical – although years ago it’s true this was doubted.
5: It is suggested that “despite the small number of studies and some heterogeneity” the study “adds to the evidence suggesting that occupational exposure to pesticides may increase the risk of ALS”. In my opinion this reworking of previously published work simply muddies the waters, by falsely claiming results not intended to be addressed in the original data collections- there are too many potential confounders and no amount of complex statistics can hide this. We are back to the era of Type 1 and Type 2 errors.
6: Only a properly designed prospective data collection can address this issue. On simple clinical grounds the hypothesis seems unlikely – ALS was described before pesticides/fungicides were invented or used; the notion that the disease is increasing in frequency is most likely to be due to an increased confidence in making the clinical diagnosis – and the initial diagnosis is quite often incorrect, it should be noted.”
Dr Nick Cole, Head of Research MND Association, UK, said:
“This is a systematic review and meta-analysis, meaning it is a review of selected literature and its statistical analysis. The study cannot establish that pesticides cause MND, only that there is a statistical association in the limited available data. The review adds a modest, updated estimate to previous, similar reviews. The evidence remains limited by a small number of studies, potential recall bias, possible exposure misclassification, and some differences between studies. Given that many included studies relied on people’s own recall of past pesticide exposure years after the fact, which can be distorted once someone has been diagnosed with a serious illness, some inflation of the reported risk estimates is possible. Readers should treat the specific percentage increases with caution.”
Dr Johnathan Cooper-Knock, NIHR Clinical Lecturer, at University of Sheffield’s School of Medicine and Population Health, said:
“The strength of this research is the use of data from eleven different studies and more than 2000 MND patients; the findings are interesting and should lead to further work.
“However, this is a retrospective analysis which uses indirect measurements of pesticide exposure and it is therefore almost impossible to know whether the effect seen is mediated by the pesticide exposure or some unseen factor which may be correlated with pesticide exposure.
“This is particularly true because we do not have a good understanding of the cause of MND except for genetic mutations, which were not measured in this study.
“Overall I think there should be some caution in interpretation of this data and additional work is necessary before advising lifestyle changes to reduce risk of MND.”
From our colleagues at The Australian SMC:
Prof Oliver Jones, Researcher in Analytical Chemistry at RMIT University, said:
“I can see this paper potentially generating some scary-sounding headlines, but it is important to take a step back and look at what was done – and what was not done.
“This paper contains no new experimental data. Instead, the authors performed a meta-analysis. This is an approach where the results of different studies on the same topic are combined to try and find an overall effect. In this case, they found a statistical association between exposure to some types of pesticides and one type of motor neuron disease (MND). They are not the first to report such an association, but association is not causation. It merely indicates what might be interesting to look at further.
“The problem with any meta-analysis is that it is only as good as the underlying studies it is based on. In this case, as the authors themselves admit, many of the underlying studies have issues, not least of which is that pesticide exposure was generally only based on answers to survey questions; it wasn’t measured directly. This means the authors have no idea how much pesticides people were actually exposed to, nor what other risk factors, such as age or lifestyle, might have had an effect. The effect was also only seen in men and not women, and although MND is more common in men than women, if pesticide exposure were a causal factor, we would expect to see some form of effect in both.
It’s unlikely that any single factor will cause MND. So, while reducing exposure to pesticides is a sensible general precaution, the paper is not a eureka moment about the risks of pesticide exposure, and people don’t need to panic.”
Prof Rachel Tan, FightMND Mid-Career Research Fellow from the FMH School of Medical Sciences, Brain and Mind Centre at The University of Sydney, said:
“This new analysis combined data from eight case-control studies conducted in the United States (x5), Canada/France (x1), Italy (x1) and Australia (x1). It found that people who had ever been exposed to pesticides at any point during their working lives were at a higher risk of developing ALS (amyotrophic lateral sclerosis) compared to those who had never been occupationally exposed.
This study’s focus on occupational exposure was a clear strength, and the overall increased risk seen when pooling eight diverse studies strengthens confidence in the findings.
However, differences in each study’s design also introduced heterogeneity that’s hard to fully account for. For instance, one of the studies included military veterans exposed to Agent Orange, a wartime exposure likely quite different from typical occupational exposure. Other studies found an increased risk of ALS linked to separate risk factors such as head trauma, which couldn’t be fully disentangled from pesticide exposure in this analysis.
Most of the included studies also relied on self-reported exposure, and these tended to show larger associations between pesticides and ALS than studies using expert assessment. As the study’s authors noted, this raises the possibility that recall bias played a role – people who already have ALS, or who already suspect a link between pesticides and the disease, may be more likely to remember and report past pesticide exposure.
Despite these considerations, these findings support the case that occupational pesticide exposure is linked to a higher risk of ALS and sets the stage for further research into which specific chemicals or pesticide components may be responsible, whether risk increases with higher doses or longer exposure (a dose-response relationship), and whether protective equipment or exposure limits can meaningfully reduce risk so we can better protect workers today and future generations from this devastating disease, which so often strikes individuals in the prime of life.”
Dr Ian Musgrave, Senior Lecturer in the Faculty of Medicine within the Discipline of Pharmacology at Adelaide University, said:
“Amyotrophic lateral sclerosis (ALS) is a devastating, incurable and progressive neurodegenerative disease involving the nerves of the motor system in the brain and spinal cord. Despite several years of research, we still do not understand the cause of ALS. However, it is most likely a combination of genetic background, lifestyle, environmental or other risk factors (head injury being a leading risk factor). There are two general forms of ALS: hereditary, with mutations in key genes, and sporadic, where the mutations in the genes associated with hereditary ALS are largely absent. Sporadic ALS is the most common form.
Environmental exposures that could trigger ALS have been widely studied; these include heavy metal exposure, air pollution, solvents and pesticides. However, while some studies of pesticides have shown an association of pesticides with ALS, most studies have shown no association.
This new study adds to our understanding by examining eight case-control studies from 1990 and performing a meta-analysis. A meta-analysis is a statistical measure used on pooled data that can combine the results of multiple independent studies and provide a stronger conclusion than the single studies alone. The study looked at control studies of confirmed ALS where occupational exposure to pesticides (fungicides, herbicides and insecticides) could be defined. These studies also attempted to control for other confounding variables (age, smoking, exposure to other chemicals).
The major finding was that, compared with no exposure, any workplace exposure to pesticides was associated with a 60% heightened risk of ALS, with evidence that high exposures had a higher risk than low exposures. Since ALS is very rare, this means only a small number of extra cases, though. While there was a significant association with the overall class, neither fungicides nor herbicides were significantly different.
Insecticides as a class were associated; however, no specific pesticides were indicated. Furthermore, as these are case-control studies, finding an association cannot confirm a causal relationship. As well, the conclusions are limited by the small number of studies involved, and factors such as recall bias in assessment of pesticide exposure.
Nonetheless, this study adds important data to the evidence that occupational exposure to pesticides may increase the risk of ALS and guide future exploration and understanding of this terrible disease.”
‘Occupational exposure to pesticides increases the risk of amyotrophic lateral sclerosis: a systematic review and meta-analysis’ by France Labrèche et al. was published in Occupational & Environmental Medicine at 23:20 UK time on Tuesday 4 August.
DOI: 10.1136/oemed-2025-110662
Declared interests
Prof Oliver Jones: “I have previously published research on pesticides in food and the environment. I have in the past received funds from the Environment Protection Authority Victoria and various Australian Water utilities for research into environmental pollution.”
Prof Rachel Tan: Rachel has not declared any conflicts of interest.
Dr Ian Musgrave: “Ian has no conflicts of interest.”
Mr Martin Scholze: “He doesn’t have any.”
Dr Wayne Carter: “I can confirm that I have no conflicts of interest associated with this quote.”
Prof Michael Swash: None received
Dr Nick Coles: “Nothing to declare with this piece of research.”
Dr Johnathan Cooper-Knock: “Dr Cooper-Knock has no interests to declare regarding this.”
For all other experts, no reply to our request for DOIs was received.
For all other experts, no reply to our request for DOIs was received.