Objectives: Water-based soluble and synthetic metalworking fluids (MWF) used in auto manufacturing may be contaminated by endotoxin from Gram-negative bacteria, a possible anticarcinogen via increased immuno-surveillance. The effectiveness of biocide, generally added to limit bacterial growth is unknown. We investigated whether an inverse relationship between lung cancer and synthetic MWF and biocide - as surrogates of endotoxin exposure - persisted in an extended follow-up of autoworkers.
Methods: A nested case-control analysis was performed within a retrospective cohort study of 46 399 auto manufacturing workers. Follow-up began in 1941 and was extended from 1985-1995. Mortality rate ratios (MRR) were estimated in Cox regression models for lung cancer as discrete and smoothed functions of cumulative exposure to synthetic MWF (mg/m (3)per year) and years exposed to biocide with both synthetic and soluble MWF. The analysis was also restricted to the subcohort hired on or after 1941 and stratified by follow-up period.
Results: The splines suggested a non-linear inverse exposure-response for lung cancer mortality with increasing endotoxin exposure. Overall, the greatest reduction in mortality was observed among those with the highest exposure [MRR 0.63, 95% confidence interval (95% CI) 0.39-0.98] at the 99 (th)percentile of exposure (15.8 mg/m (3)per year). Evidence for an inverse effect was limited to the earlier follow-up period. Effect modification by biocide was marginally significant (P=0.07); the protective effect of synthetic MWF was observed only for those who were co-exposed.
Conclusions: The protective effect of synthetic MWF against lung cancer mortality persisted through the extended period of follow-up, although attenuated, and was observed only among workers with co-exposure to biocide and synthetic MWF.