Rheumatoid arthritis is a systemic autoimmune disease associated with long-term damage and disabilities. The disease is characterized by joint inflammation and multiorgan adversities. Common risk factors for rheumatoid arthritis include older age, family history and genetics, smoking, and occupational exposure to respirable silica dust. The study highlights that smoking can interact with pesticide exposure, modifying the risk of rheumatoid arthritis in certain cases. Pesticides used in farming can also increase the risk of rheumatoid arthritis. The Agricultural Health Study, which involved approximately 89,000 licensed pesticide applicators from North Carolina and Iowa, has found a link between some specific pesticides and self-reported rheumatoid arthritis. A study published in the journal Scientific Reports provides a list of pesticides that can potentially increase the risk of rheumatoid arthritis among farmers with a lifetime exposure to pesticides.
Malathion and carbaryl, two of the pesticides linked to increased rheumatoid arthritis risk, are among the most commonly used in agricultural, public health, and residential settings in the U.S., highlighting potential risks beyond farming populations. In this study, scientists evaluated the association between pesticide use and the risk of rheumatoid arthritis in a subgroup of older Agricultural Health Study participants who were linked to Medicare fee-for-service administrative healthcare data. The cohort was predominantly white, male licensed pesticide applicators aged 67 or older, which may limit the generalizability of the findings. The study included 22,642 licensed pesticide applicators enrolled between 1993 and 1997 from North Carolina and Iowa. The risk of rheumatoid arthritis was examined in relation to the lifetime use of 45 pesticides.
The study identified 161 incident cases (0.7% of the study population) with more than two rheumatoid arthritis claims 30 days apart over a median of 8.5 years of continuous Medicare fee-for-service coverage. The median age at the first rheumatoid arthritis claim was 73 years. The risk of rheumatoid arthritis in relation to 45 specific pesticides was examined after adjusting for potential risk factors, including age, state, education, smoking, and correlated pesticides. Nine pesticides were identified that increased the risk of rheumatoid arthritis. These include four insecticides (malathion, phorate, carbaryl, and carbofuran), four herbicides (alachlor, metolachlor, S-Ethyl dipropyl thiocarbamate, and metribuzin) and one fungicide (benomyl). Exposure-response relationships, which suggest dose-dependent risks, were observed for malathion and carbofuran.
The study evaluated exposure-response trends for greater cumulative intensity-weighted lifetime days for 18 pesticides to which more than 30% of cases were exposed. For malathion, the largest risk was observed among participants with the highest cumulative exposure. In contrast, for carbofuran, the risk increased at median exposure levels. A subgroup analysis involving smokers and non-smokers identified associations for eleven pesticides among smokers and for three pesticides among non-smokers. Stronger associations were observed for carbofuran and alachlor among smokers. Conversely, malathion showed a greater effect among non-smokers. A slightly higher risk of rheumatoid arthritis due to malathion exposure was observed among non-smokers compared to that among smokers.
The study separately analyzed the risk of rheumatoid arthritis in relation to atrazine, alachlor, and metolachlor exposure, as these pesticides are frequently used together as products or tank mixtures. The findings revealed that compared to non-users, the risk of rheumatoid arthritis was elevated only among participants who used atrazine together with alachlor and/or metolachlor. The study reveals that occupational exposure to some specific pesticides can increase the risk of rheumatoid arthritis among licensed pesticide applicators. The study suggests pesticides may contribute to rheumatoid arthritis through mechanisms such as immune dysregulation, endocrine disruption and epigenetic changes, which could have broader implications for autoimmune and inflammatory diseases.
Benomyl, no longer used in the United States, is metabolized into carbendazim, which is still widely used as a fungicide and associated with developmental, reproductive, and endocrine toxicities. Previously, fungicide maneb exposure has been linked to rheumatoid arthritis among female spouses. Benomyl and maneb are carbamate fungicides, like carbaryl and carbofuran. Although smoking is a known risk factor for rheumatoid arthritis, the study suggests that pesticide exposure may increase susceptibility to immune dysregulation and autoimmunity, either independently or in combination with smoking and genetic factors. Given the observed risk, scientists highlight the need for future studies to replicate these findings in other populations and experimental conditions.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Scientific references
Parks CG, Leyzarovich D et al. Sci Reports. 2024 Dec; 14(1):29978.
Guo X et al. Environ Sci Pollut Res Int. 2023; 30(6):14413-14423.
Chittrakul J, Sapbamrer R, Sirikul W. Toxics. 2022 Apr; 10(5):207.