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Neurotoxic chemicals including several pesticides have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We investigated the relation between organochlorine pesticides and their metabolites (OCPs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in the etiology of sporadic ALS, determining for the first time their levels in cerebrospinal fluid as indicator of antecedent exposure. We recruited 38 ALS patients and 38 controls referred to an Italian clinical center for ALS care, who underwent a lumbar puncture for diagnostic purposes between 1994-2013, and had 1mL of cerebrospinal fluid available for the determination of OCPs, PCBs and PAHs. Many chemicals were undetectable in both case and control CSF samples, and we found little evidence of any increased disease risk according to higher levels of exposure. Among males >60 years, we found a slight but statistically very unstable increased ALS risk with higher levels of the congener PCB 28 and the OCP metabolite p,p'-DDE. Overall, these results do not suggest an involvement of the neurotoxic chemicals investigated in this study in disease etiology, although small numbers limited the precision of our results.

Some studies have reported an association between overexposure to selenium and risk of amyotrophic lateral sclerosis (ALS), a rare degenerative disease of motor neurons. From 1986 through 2015, we followed a cohort in Northern Italy that had been inadvertently consuming tap water with unusually high concentrations of inorganic hexavalent selenium from 1974 to 1985. We had previously documented an excess incidence of ALS in this cohort during 1986-1994. Here, we report extended follow-up of the cohort for an additional 21 years, encompassing 50,100 person-years of the exposed cohort and 2,233,963 person-years of the unexposed municipal cohort. We identified 7 and 112 incident ALS cases in the exposed and unexposed cohorts, respectively, yielding crude incidence rates of 14 and 5 cases per 100,000 person-years. A Poisson regression analysis, adjusting for age, sex and calendar year, produced an overall incidence rate ratio (IRR) for ALS of 2.8 (95% confidence interval (CI) 1.3, 6), with a substantially stronger IRR in 1986-1994 (8.2, 95% CI 2.7, 24.7) than in 1995-2015 (1.5, 95% CI 0.5, 4.7), and among women (5.1, 95% CI 1.8, 14.3) than men (1.7, 95% CI 0.5, 5.4). Overall, these results indicate an association between high exposure to inorganic selenium, a recognized neurotoxicant, and ALS incidence, with declining rates after cessation of exposure and stronger effects among women.