Association of Environmental Toxins With Amyotrophic Lateral Sclerosis

Abstract

Importance: Persistent environmental pollutants may represent a modifiable risk factor involved in the gene-time-environment hypothesis in amyotrophic lateral sclerosis (ALS).

Objective: To evaluate the association of occupational exposures and environmental toxins on the odds of developing ALS in Michigan.

Design, setting, and participants: Case-control study conducted between 2011 and 2014 at a tertiary referral center for ALS. Cases were patients diagnosed as having definitive, probable, probable with laboratory support, or possible ALS by revised El Escorial criteria; controls were excluded if they were diagnosed as having ALS or another neurodegenerative condition or if they had a family history of ALS in a first- or second-degree blood relative. Participants completed a survey assessing occupational and residential exposures. Blood concentrations of 122 persistent environmental pollutants, including organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and brominated flame retardants (BFRs), were measured using gas chromatography-mass spectrometry. Multivariable models with self-reported occupational exposures in various exposure time windows and environmental toxin blood concentrations were separately fit by logistic regression models. Concordance between the survey data and pollutant measurements was assessed using the nonparametric Kendall τ correlation coefficient.

Main outcomes and measures: Occupational and residential exposures to environmental toxins, and blood concentrations of 122 persistent environmental pollutants, including OCPs, PCBs, and BFRs.

Results: Participants included 156 cases (mean [SD] age, 60.5 [11.1] years; 61.5% male) and 128 controls (mean [SD] age, 60.4 [9.4] years; 57.8% male); among them, 101 cases and 110 controls had complete demographic and pollutant data. Survey data revealed that reported pesticide exposure in the cumulative exposure windows was significantly associated with ALS (odds ratio [OR] = 5.09; 95% CI, 1.85-13.99; P = .002). Military service was also associated with ALS in 2 time windows (exposure ever happened in entire occupational history: OR = 2.31; 95% CI, 1.02-5.25; P = .046; exposure ever happened 10-30 years ago: OR = 2.18; 95% CI, 1.01-4.73; P = .049). A multivariable model of measured persistent environmental pollutants in the blood, representing cumulative occupational and residential exposure, showed increased odds of ALS for 2 OCPs (pentachlorobenzene: OR = 2.21; 95% CI, 1.06-4.60; P = .04; and cis-chlordane: OR = 5.74; 95% CI, 1.80-18.20; P = .005), 2 PCBs (PCB 175: OR = 1.81; 95% CI, 1.20-2.72; P = .005; and PCB 202: OR = 2.11; 95% CI, 1.36-3.27; P = .001), and 1 BFR (polybrominated diphenyl ether 47: OR = 2.69; 95% CI, 1.49-4.85; P = .001). There was modest concordance between survey data and the measurements of persistent environmental pollutants in blood; significant Kendall τ correlation coefficients ranged from -0.18 (Dacthal and "use pesticides to treat home or yard") to 0.24 (trans-nonachlor and "store lawn care products in garage").

Conclusions and relevance: In this study, persistent environmental pollutants measured in blood were significantly associated with ALS and may represent modifiable ALS disease risk factors.

Figure 1

Results of logistic regression models for ALS and exposure pollutants using single and multiple chemicals. Odds ratios (●, ▲, ■) and 95% CIs (─) were examined using standardized chemical concentrations from the imputed sample (n = 284, 10 imputations), and adjusted with age, gender and educational levels. Single model shows the results of 28 regression models for individual compounds; multiple model shows the result of one regression model for 10 selected compounds. β-HCH, beta-hexachlorocyclohexane; PCB, polychlorinated biphenyl; BFR, brominated flame retardant; TBBPA, tetrabromobisphenol A; PBDE, polybromodiphenyl ether.

Figure 2

The matrix plot of Kendall's Tau correlation coefficients for self-reported and exposure pollutant data of pesticide exposures. The OCP concentrations were partitioned into 5 groups from the lowest to the highest levels; the occupational cumulative exposure to pesticides was partitioned into 4 groups from the lowest to the highest levels; the residential variables of pesticide exposures were yes/no questions. Larger circles indicate larger correlation coefficients. There was weak agreement between OCP concentrations and survey-based cumulative occupational exposure to pesticides (coefficients = −0.11 to 0.05, p-values >0.05, depending on OCP). For residential variables, the “use of pesticides in home or yard” was positively correlated with pentachlorobenzene (coefficient = 0.19, p-value <0.01), and negatively correlated with Dacthal (coefficient = −0.18, p-value = 0.01); “storing lawn care products in garage” was positively correlated with pentachlorobenzene and trans-nonachlor (coefficients = 0.15 and 0.24, p-values = 0.02 and <0.01 respectively); and “storing pesticides or lawn care products in garage” was positively correlated with pentachlorobenzene (coefficient = 0.16, p-value = 0.02).