The applicants have recently found excesses of several digestive cancers of a priori interest in a large cohort of automobile workers with exposure to metal working fluids. Since the previous application we have completed an exposure-response analysis based on internal Comparisons in the full cohort of autoworkers. Based on results of Poisson regression models, statistically significant relative risks of up to three fold were found between esophagus cancer and increasing levels of exposure to MF used in the course of grinding operations. Evidence of weaker associations, between 1.5 and 2.0, were observed between grinding and stomach and pancreatic cancer. Strong evidence was also observed for associations between straight machining fluids and rectal and larynx cancer. This revised proposal requests funds to take the next logical step to examine further the elevated risks for cancer of the esophagus, stomach, pancreas, colon and rectum in a series of nested case-control analyses. Some additions to the exposure data are proposed. By contrast with the previous proposal, however, there will be no additional case ascertainment. Estimates of duration of exposure to sulfur, chlorine, selected metals, nitrosamines and biocides are now available. Semi- quantitative estimates of exposure to sulfur and polycyclic aromatic hydrocarbones (PAH) will be developed in the scope of the proposed study. NIOSH has estimated that 1.2 million workers in the US engaged in metal grinding or machining operations are exposed to these fluids, while over 6 million workers are more generally exposed to the various components of the fluids. All of the components and common additives to be evaluated in the proposed study are known or suspect carcinogens, tumor promoters, or co-carcinogens. Better specification of the causal agent(s) in this work environment is essential for an assessment of risk associated with metal working fluids in use today.
