Diuron-induced rat urinary bladder carcinogenesis: Mode of action and human relevance evaluations using the International Programme on Chemical Safety framework

Author(s)

Da Rocha, Mitscheli Sanches ^{[1, 2]} ; Arnold, Lora L. ^[1] ; Cotrim Sartor De Oliveira, Maria Luiza ^[2] ; Ihlaseh Catalano, Shadia M. ^{[2, 3]} ; Ferragut Cardoso, Ana Paula ^[2] ; Pontes, Merielen G. N. ^[2] ; Ferrucio, Bianca ^[2] ; Dodmane, Puttappa R. ^[1] ; Cohen, Samuel M. ^[1] ; De Camargo, Joao Lauro V. ^[2]

Affiliation

^[1] Univ Nebraska Med Ctr, Omaha, NE - USA

^[2] Sao Paulo State Univ UNESP, Dept Pathol, Botucatu Med Sch, Ctr Evaluat Environm Impact Human Hlth TOXICAM, BR-18618970 Sao Paulo - Brazil

^[3] BASF, Sao Paulo - Brazil

• Document type: Review article
• Source: CRITICAL REVIEWS IN TOXICOLOGY; v. 44, n. 5, p. 393-406, MAY 2014.
• Web of Science Citations: 5

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. (AU)

• FAPESP's process: 06/60506-1 - Agriculture pesticides as risk factor: toxicologic pathology, immunology, and molecular and analytical evaluations in experimental models of single or combined exposures
• Grantee: João Lauro Viana de Camargo
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 09/02754-7 - Gene expression profiling in the urothelium of male Wistar rats exposed to the herbicide Diuron (3-(3,4-dichlorophenyl)-1,1-dimethylurea)
• Grantee: João Lauro Viana de Camargo
• Support Opportunities: Regular Research Grants