Risk of bladder cancer in male Japanese workers exposed to ortho-toluidine and other aromatic amines

Makiko Nakano, Takafumi Shinagawa, Yoko Eitaki, Kazuyuki Omae, Ayano Takeuchi, Satoko Iwasawa, Kota Fukai, Noriyuki Yoshioka, Shigeru Tanaka, Shigeki Koda, Tomotaka Sobue, Toru Takebayashi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Purpose: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). Methods: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects’ medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. Results: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7–104.3) and apparent dose–response relationships were revealed between the SIR and the surrogate exposure level in the 0–10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose–response relationships were observed. Conclusions: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.

Original languageEnglish
Pages (from-to)1427-1439
Number of pages13
JournalInternational Archives of Occupational and Environmental Health
Issue number6
Publication statusPublished - 2021 Aug


  • 2,4-Xylidine
  • Aniline
  • Bladder cancer
  • Cross-sectional study
  • SIR
  • ortho-Toluidine

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health


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