Diuron-induced rat urinary bladder carcinogenesis: Mode of action and human relevance evaluations using the International Programme on Chemical Safety framework
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Data
2014-05-01
Autores
Da Rocha, Mitscheli Sanches [UNESP]
Arnold, Lora L.
Oliveira, Maria Luiza Cotrim Sartor de [UNESP]
Ihlaseh Catalano, Shadia M. [UNESP]
Ferragut Cardoso, Ana Paula [UNESP]
Pontes, Merielen G. N. [UNESP]
Ferrucio, Bianca [UNESP]
Dodmane, Puttappa R.
Cohen, Samuel Monroe [UNESP]
Camargo, João Lauro Viana de [UNESP]
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Título de Volume
Editor
Informa Healthcare
Resumo
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.
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Palavras-chave
bladder cancer, cell proliferation, cytotoxicity, diuron, metabolites, hyperplasia, urothelium
Como citar
Critical Reviews In Toxicology. London: Informa Healthcare, v. 44, n. 5, p. 393-406, 2014.