title: Reduced lung cancer mortality and exposure to synthetic fluids and biocide in the auto manufacturing industry.
abstract: OBJECTIVE
  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.
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, Switzerland. amar.mehta@unibas.ch
authors.forename: Amar J
authors.initials: AJ
authors.lastname: Mehta
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Malloy
authors.forename: Katie M
authors.initials: KM
authors.lastname: Applebaum
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
authors.forename: Ellen A
authors.initials: EA
authors.lastname: Eisen
mesh_terms: D000328:Adult; D000395:Air Pollutants, Occupational / Q000009:adverse effects / Q000032:analysis*; D001336:Automobiles; D016022:Case-Control Studies; D004202:Disinfectants / Q000009:adverse effects / Q000032:analysis*; D004731:Endotoxins / Q000009:adverse effects / Q000032:analysis*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000401:mortality*; D008297:Male; D008669:Metallurgy; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000401:mortality*; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis / Q000517:prevention & control / Q000706:statistics & numerical data*; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D000395:Air Pollutants, Occupational; D004202:Disinfectants; D004731:Endotoxins