Diuron-induced rat urinary bladder carcinogenesis: Mode of action and human relevance evaluations using the international programme on chemical safety framework

Mitscheli Sanches Da Rocha, Lora L. Arnold, Maria Luiza Cotrim Sartor De Oliveira, Shadia M.Ihlaseh Catalano, Ana Paula Ferragut Cardoso, Merielen G.N. Pontes, Bianca Ferrucio, Puttappa R. Dodmane, Samuel M. Cohen, João Lauro V. De Camargo

Research output: Contribution to journalReview article

7 Scopus citations

Abstract

Diuron, a high volume substituted urea herbicide, induced high incidences of urinary bladder carcinomas and low incidences of kidney pelvis papillomas and carcinomas in rats exposed to high doses (2500 ppm) in a 2-year bioassay. Diuron is registered for both occupational and residential uses and is used worldwide for more than 30 different crops. The proposed rat urothelial mode of action (MOA) for this herbicide consists of metabolic activation to metabolites that are excreted and concentrated in the urine, leading to cytotoxicity, urothelial cell necrosis and exfoliation, regenerative hyperplasia, and eventually tumors. We show evidence for this MOA for diuron using the International Programme on Chemical Safety (IPCS) conceptual framework for evaluating an MOA for chemical carcinogens, and the United States Environmental Protection Agency (USEPA) and IPCS framework for assessing human relevance.

Original languageEnglish (US)
Pages (from-to)393-406
Number of pages14
JournalCritical reviews in toxicology
Volume44
Issue number5
DOIs
StatePublished - May 2014

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Keywords

  • Bladder cancer
  • Cell proliferation
  • Cytotoxicity
  • Diuron
  • Hyperplasia
  • Metabolites
  • Urothelium

ASJC Scopus subject areas

  • Toxicology

Cite this

Da Rocha, M. S., Arnold, L. L., De Oliveira, M. L. C. S., Catalano, S. M. I., Cardoso, A. P. F., Pontes, M. G. N., Ferrucio, B., Dodmane, P. R., Cohen, S. M., & De Camargo, J. L. V. (2014). Diuron-induced rat urinary bladder carcinogenesis: Mode of action and human relevance evaluations using the international programme on chemical safety framework. Critical reviews in toxicology, 44(5), 393-406. https://doi.org/10.3109/10408444.2013.877870