IntroductionWe assessed the relationship between hypospadias and proximity to agricultural pesticide applications using a GIS-based exposure method.MethodsWe obtained information for 354 cases of hypospadias born between 1998 and 2002 in eastern Arkansas; 727 controls were selected from birth certificates. We classified exposure on pounds of pesticides (estimated by crop type) applied or persisting within 500 m of each subject’s home during gestational weeks 6 to 16. We restricted our analyses to 38 pesticides with some evidence of reproductive, developmental, estrogenic, and/or antiandrogenic effects. We estimated timing of pesticide applications using crop phenology and published records.ResultsGestational age at birth [odds ratio (OR) = 0.91; 95% confidence interval (CI), 0.83–0.99], parity (OR = 0.79; 95% CI, 0.65–0.95), and delaying prenatal care until the third trimester (OR = 4.04; 95% CI, 1.46–11.23) were significantly associated with hypospadias. Risk of hypospadias increased by 8% for every 0.05-pound increase in estimated exposure to diclofop-methyl use (OR = 1.08; 95% CI, 1.01–1.15). Pesticide applications in aggregate (OR = 0.82; 95% CI, 0.70–0.96) and applications of alachlor (OR = 0.56; 95% CI, 0.35–0.89) and permethrin (OR = 0.37; 95% CI, 0.16–0.86) were negatively associated with hypospadias.ConclusionsExcept for diclofop-methyl, we did not find evidence that estimated exposure to pesticides known to have reproductive, developmental, or endocrine-disrupting effects increases risk of hypospadias. Further research on the potential effects of exposure to diclofop-methyl is recommended.