Occupational Safety and Health Research (R01)



 DESCRIPTION (provided by applicant): We propose to continue our study of the health effects of metalworking fluids (MWF) in a cohort of Michigan autoworkers by focusing on cancer incidence and applying the advanced statistical methods necessary to characterize exposure-response relations without bias due to the healthy worker survivor effect (HWSE). Though we have reported strong evidence that straight MWF exposure increases the risk of bladder cancer and melanoma skin cancer, anticipated links with respiratory, digestive and other cancers have been less clear. We now have substantial experience applying causal g-methods to control for HWSE in mortality studies of this cohort - from the first implementation of g-estimation in an occupational study, to our recent incorporation of quantitative exposure into this approach. In contrast with common perceptions about HWSE, our previous work suggests that the bias can affect studies of cancer as well as other chronic diseases. Whereas mortality follow-up began in 1941 for the original UAW-GM cohort, cancer incidence cannot be observed until decades later when two cancer registries were initiated - the Detroit SEER registry in 1973 and Michigan Cancer registry in 1985. Thus the sub-cohort of 37,786 workers eligible for this proposed cancer study includes only those who survived until the later start of follow-up, and so is left truncated If, as we have shown, MWF exposure increases mortality risk, then the cancer incidence cohort will likely include fewer subjects susceptible to the health effects of MWF exposure. We propose to apply a novel approach based on inverse weighting to address left truncation, as an additional source of healthy worker survivor bias, in this proposed study of long-term exposure to MWF in relation to risk of selected cancers. MWF are complex mixtures of oils and chemical additives widely used to cool and lubricate metal machining operations. The airborne particulate matter (PM) generated when MWF are sprayed, shares common components with traffic related PM that have been linked to lung cancer, but occurs at up to two orders of magnitude higher than ambient levels. Thus MWF pose a potential hazard to millions of workers in automobile manufacturing, specialty metals and other metal machining jobs related to electronics manufacturing, new technologies, or alternative energy. In 2010, the United Autoworkers again unsuccessfully petitioned OSHA for a MWF standard primarily on the basis of asthma and hypersensitivity pneumonitis. The goal of our proposed study, to clarify the cancer risk - both in terms of etiology and risk assessment - may be necessary spur prevention activities.