Job-related formaldehyde exposure and ALS mortality in the USA

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. Two studies found no significant association, 2 although one found a suggestion of elevated risk among the very highly exposed. 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.