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Prospective study of chemical exposures and amyotrophic lateral sclerosis
  1. M G Weisskopf1,2,3,
  2. N Morozova2,
  3. E J O’Reilly2,4,
  4. M L McCullough5,
  5. E E Calle5,
  6. M J Thun5,
  7. A Ascherio2,3,4
  1. 1
    Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
  2. 2
    Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
  3. 3
    The Channing Laboratory, Department of Medicine, Harvard Medical School and Brigham and Women’s Hospital, Boston, Massachusetts, USA
  4. 4
    Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
  5. 5
    Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia, USA
  1. Dr M G Weisskopf, Harvard School of Public Health, Department of Environmental Health, Landmark Ctr., 3rd fl. East, PO Box 15697, Boston, MA 02215, USA; mweissko{at}


Background: Although environmental toxins, including pesticides, are suspected of contributing to the risk of amyotrophic lateral sclerosis (ALS), no data exist from large prospective investigations. This study assessed the association between exposure to chemicals and risk of ALS in a prospective cohort study.

Methods: The relation between self-report of regular exposure to 11 different chemical classes or x rays and ALS mortality among over 1 million participants in the American Cancer Society’s Cancer Prevention Study II was prospectively assessed. Follow-up from 1989 through 2004 identified 617 deaths from ALS among men and 539 among women. Adjusted rate ratios (RR) were calculated using Cox proportional hazards.

Results: The RR for ALS mortality among individuals exposed to pesticides/herbicides compared with that among unexposed individuals was 1.07 (95% CI 0.79 to 1.44), but somewhat higher after excluding those with missing duration of pesticides exposure (RR 1.44; 95% CI 0.89 to 2.31; p = 0.14). A non-significant increase in ALS mortality was found among individuals who reported exposure to formaldehyde (RR 1.34; 95% CI 0.93 to 1.92). Excluding those with a missing duration of formaldehyde exposure, the RR was 2.47 (95% CI 1.58 to 3.86), and there was a strongly significant dose–response relation with increasing years of exposure (p trend = 0.0004).

Conclusions: There was little evidence for any association between pesticides/herbicide exposure and ALS. In contrast, evidence was found, suggesting an increased risk of ALS with formaldehyde exposure. Because of the longitudinal design, this result is unlikely to be due to bias, but it should nevertheless be interpreted cautiously and needs to be verified independently.

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  • Funding: This study was supported by Research Grant W81XWH-05-1-0117 from the US Department of Defense. MGW was supported by career development award K01 ES012653 from the National Institute of Environmental Health Sciences.

  • Competing interests: None.

  • Ethics approval: Ethics approval was provided by the Human Subjects Committee of the Harvard School of Public Health.

  • Patient consent: Obtained.