Mortality among pesticide applicators exposed to chlorpyrifos in the agricultural health study

Background: Chlorpyrifos is one of the most widely used organophosphate insecticides in the United States. Although the toxicity of chlorpyrifos has been extensively studied in animals, the epidemiologic data are limited. Objective: To evaluate whether agricultural chlorpyrifos exposure was associated with mortality, we examined deaths among pesticide applicators in the Agricultural Health Study, a prospective study of licensed pesticide applicators in Iowa and North Carolina. Methods: A total of 55,071 pesticide applicators were included in this analysis. Detailed pesticide exposure data and other information were obtained from self-administered questionnaires completed at the time of enrollment (1993-1997). Lifetime chlorpyrifos use was divided into tertiles. Poisson regression analysis was used to evaluate the exposure-response relationships between chlorpyrifos use and causes of death after adjustment for potential confounders. Results: A total of 1,851 deaths (588 among chlorpyrifos users) were observed during the study period, 1993-2001. The relative risk (RR) of death from all causes combined among applicators exposed to chlorpyrifos was slightly lower than that for nonexposed applicators (RR = 0.90; 95% confidence interval, 0.81-1.01). For most causes of death analyzed, there was no evidence of an exposure-response relationship. However, the relative risks for mortality from suicide and non-motor-vehicle accidents were increased 2-fold in the highest category of chlorpyrifos exposure days. Conclusions: Our findings of a possible association between chlorpyrifos use and external causes of death were based on small numbers. However, the findings may reflect a link between chlorpyrifos and depression or other neurobehavioral symptoms that deserves further evaluation.