Organophosphate Pesticide Metabolites and Mortality in U.S. Adults: Age-Modified Dose–Response Associations from a National Cohort Study

Abstract

Organophosphate pesticides (OPs) are widely used in agriculture and residential settings, raising significant concerns about their potential health risks, particularly in relation to chronic diseases such as cardiovascular diseases (CVD) and cancer. However, the long-term effects on mortality remain inconclusive. This study aimed to investigate associations between urinary OP metabolites and mortality risk in a large U.S. adult cohort. Data from 6747 adults aged ≥40 years [mean age 60.3, standard deviation (SD) 12.6] with a median follow-up of 7.7 years were analyzed. Urinary concentrations of diethyl thiophosphate (DETP), diethyl phosphate (DEP), and other OP metabolites were measured. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusted for demographic, behavioral, and clinical covariates. Over the follow-up period, 1360 deaths were recorded, including 423 from CVD and 304 from cancer. Participants in the highest quartile of DETP exposure had a 65% increased risk of all-cause mortality (HR = 1.65, 95% CI: 1.09–2.48) and a 141% increased risk of CVD mortality (HR = 2.41, 95% CI: 1.19–4.90) compared to the lowest quartile, both showing consistent positive dose–response relationships. Subgroup analyses revealed age-specific effects: DEP-associated risks were significant in adults <50 years (HR = 1.13, P-trend <0.01) but not in those ≥50 years (P-interaction <0.01). Sensitivity analyses confirmed the robustness of DETP-mortality associations (HR = 1.59 after excluding baseline CVD/cancer cases). Chronic OP exposure, reflected by these indirect urinary biomarkers, is associated with increased mortality, with heightened vulnerability in younger adults. These findings underscore the need for stricter pesticide regulation and targeted public health interventions.