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BACKGROUND: Pesticide exposure is associated with many long-term health outcomes; the potential underlying mechanisms are not well established for most associations. Epigenetic modifications, such as DNA methylation, may contribute. Individual pesticides may be associated with specific DNA methylation patterns but no epigenome-wide association study (EWAS) has evaluated methylation in relation to individual pesticides. OBJECTIVES: We conducted an EWAS of DNA methylation in relation to several pesticide active ingredients. METHODS: The Agricultural Lung Health Study is a case-control study of asthma, nested within the Agricultural Health Study. We analyzed blood DNA methylation measured using Illumina's EPIC array in 1,170 male farmers of European ancestry. For pesticides still on the market at blood collection (2009-2013), we evaluated nine active ingredients for which at least 30 participants reported past and current (within the last 12 months) use, as well as seven banned organochlorines with at least 30 participants reporting past use. We used robust linear regression to compare methylation at individual C-phosphate-G sites (CpGs) among users of a specific pesticide to never users. RESULTS: Using family-wise error rate (p DISCUSSION: We identified differential methylation for several active ingredients in male farmers of European ancestry. These may serve as biomarkers of chronic exposure and could inform mechanisms of long-term health outcomes from pesticide exposure. https://doi.org/10.1289/EHP8928, Introduction Pesticides can have both acute and long-term health effects. The mechanisms for acute health effects (e.g., cough, skin or eye irritation, headache, respiratory depression) are generally well understood. Pesticide [...]

Background: Olfactory impairment (OI) is common among older adults and independently predicts all-cause mortality and the risk of several major neurodegenerative diseases. Pesticide exposure may impair olfaction, but empirical evidence is lacking. Objective: We aimed to examine high pesticide exposure events (HPEEs) in relation to self-reported OI in participants in the Agricultural Health Study (AHS). Methods: We conducted multivariable logistic regression to examine the associations between HPEEs reported at enrollment (1993-1997) and self-reported OI at the latest AHS follow-up (2013-2015) among 11,232 farmers, using farmers without HPEEs as the reference or unexposed group. Results: A total of 1,186 (10.6%) farmers reported OI. A history of HPEEs reported at enrollment was associated with a higher likelihood of reporting OI two decades later {odds ratio (OR) = 1.49 [95% confidence interval (CI): 1.28, 1.73]}. In the analyses on the HPEE involving the highest exposure, the association appears to be stronger when there was a >4-h delay between HPEE and washing with soap and water [e.g., OR = 2.07 (95% CI: 1.48, 2.89) for 4-6 h vs. OR = 1.39 (95% CI: 1.11, 1.75) for Conclusions: HPEEs may cause long-lasting olfactory deficit. Future studies should confirm these findings with objectively assessed OI and also investigate potential mechanisms. https://doi.org/10.1289/EHP3713, Introduction The human sense of smell decreases with age. Olfactory impairment (OI), or poor sense of smell, is an understudied public health problem among older adults. OI affects up to [...]

Background: Though evidence suggests that some pesticides may have thyroid-disrupting properties, prospective studies of associations between specific pesticides and incident thyroid disease are limited. Objective: We evaluated associations between use of specific pesticides and incident hypothyroidism in private pesticide applicators in the Agricultural Health Study (AHS). Methods: Self-reported incident hypothyroidism (n = 829 cases) was studied in relation to ever-use and intensity- weighted cumulative days of pesticide use at study enrollment. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CI) using Cox proportional hazards models applied to 35,150 male and female applicators followed over 20 y. All models were stratified by state and education to meet proportional hazards assumptions (p [less than or equal to] 0.10 for age x covariate interactions). Models of pesticides that did not meet proportional hazards assumptions were stratified by median attained age (62 y). Results: Hypothyroidism risk was significantly increased with ever- vs. never-use of four organochlorine insecticides (aldrin, heptachlor, and lindane among participants with attained age >62 y; chlordane in all participants), four organophosphate insecticides (coumaphos in those >62 y; diazinon, dichlorvos, and malathion in all participants) and three herbicides (dicamba, glyphosate, and 2,4-D in all participants). HRs ranged from 1.21; 95% CI: 1.04, 1.41 (chlordane) to 1.54; 95% CI: 1.23, 19.4 (lindane in those >62 y). Hypothyroidism risk was greatest among those with higher intensityweighted lifetime days of using chlordane, lindane, coumaphos (over age 62), diazinon, permethrin, and 2,4-D. Conclusions: Our findings support associations between exposure to several pesticides and increased hypothyroidism risk. These findings are generally consistent with prior analyses of prevalent hypothyroidism in the AHS., Introduction Thyroid diseases are common in the United States (U.S.); and with prevalence estimates of 5-9% (overt and subclinical disease combined), hypothyroidism is the most common thyroid disease (Garber et [...]