CHICAGO— Preliminary results suggest that exposure to the chemical formaldehyde may increase the risk for amyotrophic lateral sclerosis (ALS), according to a report at the 60th Annual Meeting of the American Academy of Neurology. Researchers found that people with more than 10 years of exposure to formaldehyde had a 4.1 times increased risk for ALS, compared with those who had no exposure.
“While pesticides have been thought to contribute to the development of ALS, this is the first time that formaldehyde has been identified as a potential risk factor,” commented Marc Weisskopf, PhD, Assistant Professor of Environmental and Occupational Epidemiology at Harvard School of Public Health in Boston.
Formaldehyde is used in particleboard and other wood products, permanent press fabrics, glues, photography chemicals, and other household products, such as cosmetics and shampoo. It is also used as a tissue preservative in medical laboratories and mortuaries and as an industrial disinfectant. About 20 years ago, the US Environmental Protection Agency designated high levels of formaldehyde as a probable carcinogen.
Exposure to Chemicals and Risk for ALS
Prior research has suggested that environmental toxins, including pesticides, may be associated with ALS. This notion has been backed by case-control and genetic studies implicating genes involved in pesticide detoxification, said Dr. Weisskopf. However, the findings have been contradictory, and there have been no large prospective studies to support this hypothesis.
In the present investigation, Dr. Weisskopf’s group prospectively examined the relationship between regular exposure to 12 types of chemicals and ALS in 987,229 individuals who participated in the American Cancer Society–sponsored Cancer Prevention Study II. Participants were asked about their exposure to chemicals, including formaldehyde, in 1982, and they were then followed for approximately 15 years. The researchers also analyzed exposure to asbestos, acids/solvents, coal or stone dust, coal tar pitch/asphalt, diesel engine exhaust, dyes, gasoline exhaust, pesticides/herbicides, textile fibers/dust, wood dust, and x-ray/radioactive material.
Overall, 617 men and 539 women died from ALS during the follow-up period. Regular formaldehyde exposure increased ALS risk by 34%. In addition, the longer the self-reported exposure to formaldehyde, the higher the risk for ALS. Thus, compared with those reporting no exposure, the adjusted relative risk for ALS was 1.5 in individuals who reported less than four years of exposure, 2.1 in those with four to 10 years of exposure, and 4.1 in those with more than 10 years of exposure. Overall, 2.6% of participants reported that they had been exposed to formaldehyde. By contrast, there was limited evidence for an association between ALS and pesticides/herbicides.
The study also found that an increased risk for ALS was seen with certain jobs. Nearly 25% of beauticians reported that they were exposed to formaldehyde. Pharmacists, morticians, radio/lab technicians, dentists, firemen, photographers, printers, doctors, and nurses also reported high rates of formaldehyde exposure. Individuals in these high-exposure jobs had a 28% greater risk for ALS.
There are several possible mechanisms for formaldehyde neurotoxicity, said Dr. Weisskopf. These include hyperexcitability of dorsal horn neurons, reduced excitability of the isolated phrenic nerve, prefrontal cortex/hippocampal neurotoxicity, a decrease in superoxide dismutase activity, an increase in malondialdehyde, and toxic tau protein misfolding.
A Causal Relationship for ALS and Formaldehyde?
Dr. Weisskopf noted that the longitudinal design of the study minimizes the possibility that the results are due to bias. Additional strengths of the study include its large size and uniform case ascertainment, as well as the fact that other factors that might contribute to ALS were controlled for, including sex, smoking status, military service, level of education, alcohol intake, occupation, vitamin E supplement use, and exposure to other chemicals.
Possible limitations of the study include small numbers in some exposure categories, as well as self-assessment of exposure. In addition, only mortality data were used to identify ALS cases. Dr. Weisskopf noted, however, that because death certificates have been reported to accurately identify 70% to 80% of ALS-related deaths, they might be a reasonable surrogate for ALS incidence, due to the short survival time associated with the disease.
Dr. Weisskopf emphasized that the findings are preliminary and do not establish a causal relationship between formaldehyde and ALS. “At the moment, it is premature to make broad public health recommendations, and corroboration of the data is needed,” he concluded.