title: Diuron-induced rat urinary bladder carcinogenesis: mode of action and human relevance evaluations using the International Programme on Chemical Safety framework.
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.
authors: University of Nebraska Medical Center , Omaha, NE , USA.
authors: Mitscheli Sanches
authors: MS
authors: Da Rocha
authors: Lora L
authors: LL
authors: Arnold
authors: Maria Luiza Cotrim Sartor
authors: ML
authors: De Oliveira
authors: Shadia M Ihlaseh
authors: SM
authors: Catalano
authors: Ana Paula Ferragut
authors: AP
authors: Cardoso
authors: Merielen G N
authors: MG
authors: Pontes
authors: Bianca
authors: B
authors: Ferrucio
authors: Puttappa R
authors: PR
authors: Dodmane
authors: Samuel M
authors: SM
authors: Cohen
authors: João Lauro V
authors: JL
authors: De Camargo
mesh_terms: D000818:Animals; D062067:Chemical Safety; D004195:Disease Models, Animal; D004237:Diuron / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006540:Herbicides / Q000493:pharmacokinetics / Q000633:toxicity*; D006801:Humans; D051381:Rats; D066007:Toxicokinetics; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000473:pathology*; D019459:Urothelium / Q000187:drug effects / Q000473:pathology
chemical_list: D006540:Herbicides; D004237:Diuron