Pesticide exposure and amyotrophic lateral sclerosis

Abstract

Our objectives were to summarize literature on the association of amyotrophic lateral sclerosis (ALS) with pesticides as a group and to evaluate associations of ALS with specific pesticides. We conducted a meta-analysis of published studies of ALS and pesticides as a group and investigated the association of ALS with specific pesticides, using data from the Agricultural Health Study (AHS), a cohort including 84,739 private pesticide applicators and spouses. AHS participants provided information on pesticide use at enrollment in 1993–1997. In mortality data collected through February 2010, ALS was recorded on death certificates of 41 individuals whom we compared to the remaining cohort (controls), using unconditional logistic regression adjusted for age and gender to calculate odds ratios (ORs) and 95% confidence intervals. In the meta-analysis, ALS was associated with use of pesticides as a group (1.9, 1.1–3.1). In the AHS, ALS was not associated with pesticides as a group, but was associated with use of organochlorine insecticides (OCs) (1.6, 0.8–3.5), pyrethroids (1.4, 0.6–3.4), herbicides (1.6, 0.7–3.7), and fumigants (1.8, 0.8–3.9). ORs were elevated forever use of the specific OCs aldrin (2.1, 0.8–5.1), dieldrin (2.6, 0.9–7.3), DDT (2.1, 0.9–5.0), and toxaphene (2.0, 0.8–4.9). None of these associations was statistically significant. Similar results were observed in an analysis restricted to men. In conclusion, the meta-analysis suggests that ALS risk is associated with use of pesticides as a group, and our analysis of AHS data points to OC use in particular. The latter results are novel but based on a small number of cases and require replication in other populations.

Introduction

ALS is a rapidly progressive neurodegenerative disease affecting motor neurons in the brain and spinal cord, with symptoms including muscular weakness, spasticity, and hyperreflexia. The condition is rare, with an annual incidence of 1–2 per 100,000; incidence is greater in men and increases with age.

The etiology of ALS is not well understood. Approximately 10% of ALS cases have a family history of ALS, likely involving genetic factors. Environmental factors including metals, organic solvents, and pesticides may also contribute to ALS (Sutedja et al., 2009). Exposure to pesticides as a group has been explicitly evaluated in seven case–control studies (Bonvicini et al., 2010, Chancellor et al., 1993, Deapen and Henderson, 1986, Gunnarsson et al., 1992, McGuire et al., 1997, Morahan and Pamphlett, 2006, Savettieri et al., 1991) and one cohort study (Weisskopf et al., 2009); exposure was generally associated with increased risk in the case–control studies although the relationship was not always statistically significant. None of these studies evaluated the role of specific pesticides in ALS etiology.

To summarize existing findings, we conducted a meta-analysis of published studies of ALS and exposure to pesticides as a group. We then evaluated the association of ALS with specific pesticides, using data from the Agricultural Health Study (AHS), a cohort of licensed pesticide applicators and their spouses. Our study provides the first analytic evaluation of the role of specific pesticides in ALS.