Elevated mortality from nonalcohol-related chronic liver disease among female rubber workers: Is it associated with exposure to nitrosamines?

Background Despite several case reports describing fiver toxicity of nitros amines and the fact that some N-nitroso compounds are used to induce cirrho sis of the liver in animal models, this association has nor been investigat ed in epidemiological studies. Methods A cohort of 2,875female rubber workers who were active on January 1 , 1976, or hired thereafter and who had been employed;for at least I year i n one of five plants producing tires or technical rubber goads was followed for mortality from January, 1976, through December 1991. Work histories we re reconstructed using routinely documented "cost center codes" and classif ied into six work areas. Age and calendar year standardized mortality ratio s (SMR) and 95% confidence intervals (95% CI) were calculated and stratifie d by plant, work area, war of hire, and years of employment in the respecti ve work area. Results The excess mortality from cirrhosis of the liver was most pronounce d for nonalcohol-related cirrhosis of the liver (ICD-9 571.4-571.9: 10 deat hs, SMR 202; 95% CI 97-372). Mortality from alcohol-related cirrhosis of th e liver (ICD-9 571.0-571.3: 3 deaths, SMR 153; 95% CI 31-446) and from othe r alcohol-related diseases (organic psychoses, injury, and poisoning) was n ot statistically significantly elevated. All 10 cases nonalcohol-related ci rrhosis had worked in production of technical rubber goods (SMR 279; 95% CI 134-514) and risks increased with earlier years of hire and with longer du ration of employment in this work area. Discussion Although our results must be interpreted with caution, they sugg est that the observed excess deaths from cirrhosis of the liver are associa ted with occupational risk factors. In light of additional evidence from ca se reports and animal data, exposure to nitrosamines may be a plausible ris k factor for the observed excess mortality. (C) 1999 Wiley-Liss, lnc.