Pesticides Applied to Crops and Amyotrophic Lateral Sclerosis Risk in the U.S

Background: Environmental exposures are implicated in the etiology of amyotrophic lateral sclerosis (ALS). Application of insecticides, herbicides, and fungicides with neurotoxic properties to crops is permitted in the U. S., however reporting of the quantities is government mandated. Objective: To identify pesticides that may be associated with ALS etiology for future study. Methods: We geospatially estimated exposure to crop-applied pesticides as risk factors for ALS in a large de identified medical claims database, the SYMPHONY Integrated Dataverse (R). We extracted residence at diagnosis of ~26,000 nationally distributed ALS patients, and matched non-ALS controls. We mapped county-level U. S. Geological Survey data on applications of 423 pesticides to estimate local residential exposure. We randomly broke the SYMPHONY dataset into two groups to form independent discovery and validation cohorts, then confirmed top hits using residential history information from a study of NH, VT, and OH. Results: Pesticides with the largest positive statistically significant associations in both the discovery and the validation studies and evidence of neurotoxicity in the literature were the herbicides 2,4-D (OR 1.25 95 % CI 1.17-1.34) and glyphosate (OR 1.29 95 %CI 1.19-1.39), and the insecticides carbaryl (OR 1.32 95 %CI 1.23-1.42) and chlorpyrifos (OR 1.25 95 %CI 1.17-1.33). Significance: Our geospatial analysis results support potential neurotoxic pesticide exposures as risk factors for sporadic ALS. Focused studies to assess these identified potential relationships are warranted.