Occupational Exposure to Formaldehyde Linked to Increased ALS Risk

No Significant Association Between ALS and Pesticide, Herbicide Exposure

Caroline Cassels

April 21, 2008

April 21, 2008 (Chicago, Illinois) — Preliminary results from a large prospective population-based study have linked occupational exposure to formaldehyde with an increased rate of amyotrophic lateral sclerosis (ALS).

Presented here at the American Academy of Neurology 60th Annual Meeting, investigators at Harvard University, in Boston, Massachusetts, found that individuals exposed to formaldehyde for 10 years or more had a 4.1-fold increased rate of ALS compared with those who had no exposure to the chemical.

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"This finding was somewhat surprising, because formaldehyde has not been raised as an issue in ALS before," study investigator Marc Weisskopf, PhD, told reporters attending a press conference.

Although the dose-response finding is definitely a "red flag," Dr. Weisskopf emphasized that these results are preliminary and require further follow-up.

"The bottom line is we went into this [study] particularly interested in pesticides and herbicides, and we came away with really only limited evidence suggesting an association. But more surprisingly, we really were struck by the association between formaldehyde and ALS and, in particular, the strength of the dose-response relationship in terms of years of exposure," he said.

Although some previous research has suggested that pesticides and herbicides play a role in ALS etiology, a population-based case-control study in the 1990s found that individuals who self-reported occupational exposure to agricultural chemicals had a 2-fold increased risk for the disease.

A 2007 study from researchers in Australia found a 60% increased risk for ALS among individuals who self-reported herbicide and pesticide exposure. When such exposures were reported to be industrial, the risk was almost 6 times higher.

However, he added, many other studies have shown no association between agricultural chemicals and ALS.

Difficult to Study

Although it is the third most common neurodegenerative disease in the United States, ALS is still relatively rare and therefore difficult to study. As a result, said Dr. Weisskopf, there have been no large prospective cohort studies conducted.

To prospectively assess the association between self-reported regular exposure to different classes of chemicals, the researchers used data from the American Cancer Society's Cancer Prevention Study II (CPS II).

The CPS II cohort began in 1982 and included more than 1 million individuals who completed a questionnaire about 12 classes of chemical exposures at study outset; it was then followed for death through linkage to the National Death Index.

For the ALS analysis, the investigators began follow-up of the cohort in 1989 (before this date, ALS deaths were not coded separately). All subjects with no illness at baseline who could possibly have been ALS were included.

Between 1989 and 2004, a total of 1156 ALS deaths were recorded. Overall, individuals who reported that they had regular exposure to formaldehyde were 34% more likely to develop ALS than those with no exposure to formaldehyde.

Further, when investigators analyzed the data according to length of exposure to formaldehyde, they found a "very strong dose response."

Jobs and Formaldehyde Exposure

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Adjusted analyses revealed that individuals who were exposed for less than 4 years had a 50% higher rate of ALS. Those exposed for between 4 and 10 years had a 110% higher rate, and those with 10 or more years of formaldehyde exposure had just over a 4-fold increased rate of ALS.

Of the total study cohort, 2.6% of individuals reported exposure to formaldehyde. When investigators analyzed the data to determine the highest formaldehyde exposures by occupation, they found that beauticians topped the list.

Following beauticians were morticians, pharmacists, chemists, radio/lab technicians, doctors/veterinarians, dentists, firefighters, photographers/printers, and nurses.

At this point, said Dr. Weisskopf, there are no public health implications or recommendations other than a need for further study to confirm or refute these findings.

"As far as we know, this finding has not been reported before, so at this stage we are treating it as a very intriguing, preliminary result that we hope gets followed up in other settings to see whether it holds up," he said.

The study was supported by a grant from the US Department of Defense. The authors have disclosed no relevant financial relationships.

American Academy of Neurology 60th Annual Meeting: Abstract S25.005. Presented April 16, 2008.


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