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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| Authors: | 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 |
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| Affiliation: | 1. University of Nebraska Medical Center,Omaha, NE, USA;2. Department of Pathology, Center for Evaluation of the Environmental Impact on Human Health (TOXICAM), Botucatu Medical School, S?o Paulo State University (UNESP),Botucatu, S?o Paulo, Brazil;3. Department of Pathology, Center for Evaluation of the Environmental Impact on Human Health (TOXICAM), Botucatu Medical School, S?o Paulo State University (UNESP),Botucatu, S?o Paulo, Brazil;4. BASF, S?o Paulo, Brazil |
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| 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. |
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| Keywords: | bladder cancer cell proliferation cytotoxicity diuron metabolites hyperplasia urothelium |
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