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Animal models and in vitro experiments suggest neurotoxic effects of formaldehyde that may be relevant for amyotrophic lateral sclerosis (ALS). Formaldehyde induces neuronal τ protein misfolding and aggregation, leading to neuronal apoptosis. Formaldehyde also increases mitochondrial membrane permeability and causes oxidative damage partly by reducing superoxide dismutase activity, mechanisms implicated in ALS.
Studies have had mixed findings regarding formaldehyde exposure and ALS mortality. A large prospective study found an elevated risk that did not quite reach statistical significance, but found a strong dose–response relationship with total years of exposure.1 Two studies found no significant association,1 ,2 although one found a suggestion of elevated risk among the very highly exposed.2 We examine here the association of ALS mortality with job-related formaldehyde exposure in the National Longitudinal Mortality Study (NLMS), a US-representative cohort with occupation data collected prospectively.
The NLMS is a multistage probability sample of the civilian non-institutionalised population (response rate ∼96%). We included the 794 541 men and 674 694 women who were at ages 25+ when surveyed. Participants were asked about their current or most recent job. We used a formaldehyde exposure matrix constructed by industrial hygienists at the National Cancer Institute and previously described.3 Intensity and probability of formaldehyde exposure were calculated for each occupation and industry, and coded as none, low, medium or high.3 Intensity reflected the frequency and level of formaldehyde exposure; probability reflected the likelihood of any formaldehyde exposure.
NLMS records were matched to the National Death Index (NDI, 1979–2011) to obtain cause of death. ALS deaths were defined as International Classification of Diseases Ninth and 10th Edition (ICD)-9 335.2 …