Evidence map›Paper›PMID 39930727›Full record

ReviewJournal of occupational health2025

Occupational health topics series on the effects of chemicals: epidemiological and toxicological risk assessments of ortho-toluidine for bladder cancer.

Makiko Nakano, Min Gi, Tatsushi Toyooka, Shugo Suzuki, Hideki Wanibuchi, Toru Takebayashi

Erratum issuedAbstract readReview
In one paragraph

Review in Journal of occupational health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Makiko NakanoDivision of Epidemiological Research for Chemical Disorders, Research Center for Chemical Information and Management, National Institute of Occupational Safety and Health, Kawasaki, Japan.
Min GiDepartment of Environmental Risk Assessment, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Tatsushi ToyookaToxicological Test Methodology Development Group, National Institute of Occupational Safety and Health, Fujisawa, Japan.
Shugo SuzukiDepartment of Molecular Pathology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Hideki WanibuchiDepartment of Environmental Risk Assessment, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan.
Toru TakebayashiDepartment of Preventive Medicine and Public Health, Keio University School of Medicine, Tokyo, Japan.ORCID 0000-0002-8268-8026

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesOur aim was to report integrative evidence for the health risk assessment of ortho-toluidine (OT) in bladder cancer in a mini-review of the recent studies of humans, experimental animals, and OT skin permeability.

methodsBladder cancer cases were identified in workers in Japan who were occupationally exposed in 2014-2017 to aromatic amines, primarily to the human carcinogen OT.

resultsA key epidemiological study of 98 aromatic amine-exposed workers in Japan showed a clear OT exposure-response relationship with a standardized incidence ratio. A rat model experimental study also indicated that OT and acetoaceto-o-toluidine are potent bladder carcinogens. Multiple mechanisms of OT-related bladder cancer have been proposed: metabolic activation to reactive metabolites that bind DNA and proteins, mutagenicity, oxidative DNA damage, chromosomal damage, and cytotoxicity by OT. Recent comprehensive analyses of DNA adducts in rats identified a number of common oxidative DNA adducts, including 8-OHdG, in the rat urothelium and indicated that oxidative stress may play a crucial role in the development of urinary cancer caused by OT. The skin permeability of 6 aromatic amines (o-toluidine, aniline, p-toluidine, o-anisidine, 2,4-dimethylaniline, and o-chloroaniline) was examined with the use of a 3-dimensional (3D) reconstructed human skin model; ~70%-80% of the 6 aromatic amines had permeated through the 3D skin within 8 hours. Genotoxic potency testing in a human urothelial cell line using γ-H2AX, a marker of DNA damage, suggested that OT exhibited strong γ-H2AX generation.

conclusionsProlonged dermal exposure to OT along with other genotoxic aromatic amines over many years may contribute to the development of bladder cancer.

Indexed as

CarcinogensOccupational ExposureToluidinesUrinary Bladder NeoplasmsAnimalsHumansJapanRatsRisk AssessmentSkin2-toluidineCarcinogensToluidinesanimal modelbladder cancerepidemiologyortho-toluidineskin permeability

Identifiers

PMID39930727
PMCPMC11858003

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.