Article Text

Job-related formaldehyde exposure and ALS mortality in the USA
  1. Andrea L Roberts1,
  2. Norman J Johnson2,
  3. Merit E Cudkowicz3,4,
  4. Ki-Do Eum5,
  5. Marc G Weisskopf5,6
  1. 1Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  2. 2United States Census Bureau, Washington DC, USA
  3. 3Harvard Medical School, Boston, Massachusetts, USA
  4. 4Department of Neurology, MGH MDA ALS Clinic, Massachusetts General Hospital, Boston, Massachusetts, USA
  5. 5Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  6. 6Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
  1. Correspondence to Dr Andrea L Roberts, Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Social and Behavioral Sciences, 677 Huntington Avenue, Boston, MA 02115, USA; aroberts{at}

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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 or ICD-10 G12.2 as the underlying or contributing cause. Data were …

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  • Disclosures This paper is released to inform interested parties of research and to encourage discussion. Any views expressed on statistical, methodological, technical, or operational issues are those of the authors and not necessarily those of the US Census Bureau.

  • Contributors All authors made substantial contributions to the conception or design of the work, or to the acquisition, analysis or interpretation of data for the work; to the drafting of the manuscript or revised it critically for important intellectual content; and approved the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. NJJ had full access to the data and takes responsibility for accuracy of the data analyses.

  • Funding This work was supported by grant #MDA239243 from the Muscular Dystrophy Association, NIH grant #NS 082105, and funding from the National ALS Registry programme of the Agency for Toxic Substances and Disease Registry (ATSDR). The funding organisations played no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; or preparation, review or approval of the manuscript. NJJ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

  • Competing interests None declared.

  • Ethics approval Harvard School of Public Health.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Data are available through the US Census Bureau.