Retrospective Assessment of Occupational Exposures for the GENEVA Study of ALS among Military Veterans

Objective This paper describes the retrospective exposure assessment conducted to assess occupational exposures for the Genes and Environmental Exposures in Veterans (GENEVA) study, a case-control study investigating the joint contribution of genetics and environmental exposures to the risk of amyotrophic lateral sclerosis (ALS) among military veterans. Methods Occupational histories for 1597 study participants collected as part of the GENEVA study were the basis for this retrospective exposure assessment. The data set included 15528 jobs held from 1924 to 2010, representing 4539 unique industry and occupation (I&O) combinations. Three industrial hygiene experts were recruited to independently rate occupational exposures to specific agents previously associated with an increased risk of ALS. Utilizing information on industry, job title, tasks performed, and materials used for each job held, raters assigned exposures associated with each I&O for the 'current time' defined as the period after 1995 (post-1995). The exposure assessment targeted agents identified as potential occupational risk factors for ALS. Experts rated semi-quantitatively exposure intensity in five exposure categories (0-4) for Group A agents (lead, formaldehyde, hydrocarbon solvents, and chlorinated solvents) and qualitatively as yes/no (1/0) exposed for Group B agents (mercury, selenium, arsenic, polychlorinated biphenyls, electromagnetic field, pesticides, and viral agents). Confidence scores (0-3) were reported for every I&O rated based on raters' experience with that industry and/or job. Each I&O was assigned an average exposure score of the raters and an alternative exposure rating was developed for each I&O by excluding low confidence (<2) scores before averaging. Exposure reconstruction for jobs held pre-1995 was done by comparing exposure data extracted from the OSHA Chemical Exposure and Health Database (CEHD) during pre-1995 and post-1995. For agents with limited exposure data in the CEHD, pre-1995 exposures were determined based on raters' judgment. Results The proportion of I&O combinations determined to be 'exposed' ranged from 0.1 to 26% across different agents, with the highest values corresponding to hydrocarbon solvents and the lowest to selenium. Industries with the highest proportion of exposed records include manufacturing, utilities, healthcare, and military with non-combat jobs. Analyses for raters' reliability showed the best agreement between the raters when rating exposure to viral agents (kappa = 0.67), hydrocarbon solvents (kappa = 0.53), and lead (kappa = 0.50). The proportion of 'exposed' I&O combinations increased for hydrocarbon solvents, chlorinated solvents, and pesticides when exposure ratings were adjusted by raters' confidence. Compared to post-1995, exposures in the earlier period (pre-1995) were deemed higher or the same for most of the agents and lower for formaldehyde and electromagnetic field exposures. Conclusions Our results indicate that using raters' confidence assessment in determining exposure scores increases both the proportion of I&O combinations regarded as exposed and the intensity scores, suggesting raters tend to be conservative in their assessment when they lack detailed knowledge of an industry or job.