title: Increased risk of lung cancer associated with occupational exposure to benzidine and/or beta-naphthylamine.
abstract: OBJECTIVE
  To evaluate non-urological cancer risks associated with benzidine (BZ) and beta-naphthylamine (BNA), a historical cohort study was undertaken.
  
  
  METHODS
  A total of 224 male workers exposed to BZ/BNA from a single factory were followed from 1953 to 2011. To estimate BZ/BNA exposure dose, duration of exposure (DOE) was defined as duration of employment between 1953 and 1972, the period when BZ and BNA were produced and used at this factory. Subjects were dichotomized (into long- and short-term groups) based on the median of DOE. Cancer-specific standardized incidence ratios (SIRs) were calculated using national and regional incidence rates as reference. Smoking history was obtained through questionnaires and other sources. Association between lung cancer (LC) or bladder cancer (BC) incidence and DOE was assessed using Cox's proportional hazards model.
  
  
  RESULTS
  Vital status follow-up was successful for 216 (96.4%). Follow-up duration averaged 44.0 (SD 10.7) years. Increased SIRs based on national rates were found for all cancers (81 cases, SIR = 1.58, 95% CI 1.26-1.98), LC (18 cases, SIR = 2.58, 95% CI 1.53-4.07), and BC (7 cases, SIR = 4.70, 95% CI 1.89-9.67). Among workers with >20 years after first exposure, the SIR for LC was statistically elevated in the long DOE group (15 cases, SIR = 3.34, 95% CI 1.87-5.51). After adjustment for smoking, exposure to bis(chloromethyl) ether, and age at first exposure, a marginally significant hazard ratio (HR) was observed for the long DOE group (adjusted HR = 3.02, 95% CI 0.84-10.93, p = 0.091), compared to the short DOE group. DOE did not affect BC incidence.
  
  
  CONCLUSIONS
  This study confirms the high risk of LC besides BC, suggesting that BZ/BNA have the potential to cause LC.
authors.affiliation: Department of Community Health and Epidemiology, Nara Medical University, Shijo-cho 840, Kashihara City, Nara, zip code 6348521, Japan, tkimiko@naramed-u.ac.jp.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Tomioka
authors.forename: Kenji
authors.initials: K
authors.lastname: Obayashi
authors.forename: Keigo
authors.initials: K
authors.lastname: Saeki
authors.forename: Nozomi
authors.initials: N
authors.lastname: Okamoto
authors.forename: Norio
authors.initials: N
authors.lastname: Kurumatani
mesh_terms: D015081:2-Naphthylamine / Q000633:toxicity*; D000328:Adult; D000368:Aged; D001391:Azo Compounds / Q000633:toxicity; D001560:Benzidines / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002617:Chemical Industry / Q000706:statistics & numerical data*; D015331:Cohort Studies; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000139:chemically induced / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000453:epidemiology*; D016273:Occupational Exposure / Q000009:adverse effects*; D016016:Proportional Hazards Models; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D013997:Time Factors
chemical_list: D001391:Azo Compounds; D001560:Benzidines; D002273:Carcinogens; C029876:benzidine; D015081:2-Naphthylamine