A mixtures approach to solvent exposures and amyotrophic lateral sclerosis: a population-based study in Denmark

Abstract

Studies of occupational solvent exposures and amyotrophic lateral sclerosis (ALS) have been conflicting. We conducted a population-based case-control study of mixed occupational solvent exposures and ALS. Using the Danish National Patient Registry, we identified ALS cases in Denmark from 1982 to 2013, and matched them to 100 controls based on sex and birth year. We estimated cumulative exposures to solvents (benzene, methylene chloride, toluene, trichloroethylene, perchloroethylene, and 1,1,1-trichloroethane) via job exposure matrices and applied them to occupational history from the Danish Pension Fund. Sex-stratified conditional logistic regression analyses revealed higher adjusted odds of ALS for men with exposure to benzene (aOR = 1.20; 95% CI 1.02, 1.41) and methylene chloride (aOR = 1.23; 95% CI 1.07, 1.42). We used weighted quantile sum regression to explore combined solvent exposures and risk of ALS in exposed subjects and found increased odds of 26 to 28% in all exposure lag periods for every one-unit increase in the mixture index in men. Weights of methylene chloride predominated the mixture index in all lag periods. Our study suggests an increased risk of ALS in men exposed to multiple solvents, with the greatest influence being from methylene chloride. These findings highlight the need to utilize mixtures analysis when considering co-occurring exposures.

Keywords: Amyotrophic lateral sclerosis (ALS); Mixtures; Motor neuron disease; Occupational exposures; Solvents.

Figure 1.. Analysis of any 5-year lagged exposure to solvents and ALS cases status in Denmark, 1982–2013.

Data are the odds ratios (95% confidence intervals) of ALS by individual solvent exposures. All models were adjusted for socioeconomic status and residential location at the index date. Abbreviations are as follows: MCH = Methylene chloride, PER = Perchloroethylene, TCE = trichloroethylene, TRI = 1,1,1- Trichloroethane

Figure 2:. Analyses of 5-year lagged cumulative exposure to solvents and ALS case status in Denmark, 1982–2013.

Data are the odds ratios (95% confidence intervals) of ALS for quartile categories of individual solvent exposures compared to those with no exposures. All models were adjusted for SES and residential location at the index date. Results are stratified by sex. Abbreviations are as follows: MCH = Methylene chloride, PER = Perchloroethylene, TCE = Trichloroethylene, TRI = 1,1,1-Trichloroethane

Figure 3.. Heat map of correlations between solvents.

Data are correlation coefficients for correlations between individual cumulative solvent exposures in subjects with any solvent exposure. Results are stratified by sex.

Figure 4.. Association between solvent levels and risk of ALS based on weighted quantile sum (WQS) regression analysis.

Bar graphs indicate the magnitude of WQS weight for each solvent. Data are the odds ratios (95% confidence intervals) associations between ALS and derived solvent mixture index scores by exposure lag periods. Results are stratified by sex. All models were adjusted for age, SES, and residential location at the index date.