Occupational Formaldehyde And Als

Abstract

Introduction: Formaldehyde is a neurotoxic organic compound. Recently it has been associated with the risk of amyotrophic lateral sclerosis (ALS) in epidemiologic studies. We investigated the relationship between occupational exposure to formaldehyde and the incidence of ALS in the Danish population. Methods: We obtained records for the 3,650 incident cases of ALS in the Danish Hospital Register between 1982 and 2009. Each case was matched to 10 age- and sex-matched population controls alive on the date of the case diagnosis. Occupational records were obtained from the Danish Pension fund, which were then merged to a previously validated job exposure matrix to obtain the annual estimated exposure for each individual from 1964 to 2009. We employed two methods to investigate the relationship: lagged cumulative exposure and time-varying cumulative exposure adjusted for work history. Finally, we investigate the use of g-methods to account for a potential healthy worker survivor effect (HWSE). Results: Among controls, 25.9% (n=9,458) had any estimated exposure to formaldehyde between 1964 and the index date; in these individuals, the median cumulative exposure was 0.08 ppm (IQR: 0.03-0.24). Overall, those with any exposure to formaldehyde had a slightly but non-significantly elevated rate of ALS (RR=1.05; 95% CI 0.97-1.14). All quartiles of exposure were elevated, though not significantly. Adjustment for time-varying work status did not change the results. However, we observed associations that are consistent with the presence of the HWSE, and we observed a lowering of ALS incidence above the 99th percentile of exposure. Conclusions: We observed a slightly increased rate of ALS in those exposed to formaldehyde. Although adjustment for time-varying work history did not alter the association, it is an imperfect method to control for the HWSE. We will investigate and discuss the use of g-methods in a nested case-control study to further adjust for the HWSE.