Dose-response of diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] in the urothelial mucosa of Wistar rats.

Abstract

Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a herbicide that induced urothelial tumors in the urinary bladder of Wistar rats fed 2500ppm during a long-term study. The currently suggested non-genotoxic mode of action (MOA) of diuron encompasses in succession urothelial necrosis induced by direct cytotoxicity, regenerative cell proliferation and sustained urothelial hyperplasia that increases the likelihood of neoplasia development. This study evaluated the dose-response profile of urothelial histological and ultrastructural lesions induced by diuron. Sixty male Wistar rats were fed ad libitum diuron mixed in the diet at 0, 60, 125, 500, 1250, or 2500ppm for 20 weeks. The incidences of urothelial simple hyperplasia and the cell proliferation index were significantly increased in the diuron-fed 1250 and 2500ppm groups. By scanning electron microscopy, the incidences and severity of lesions were significantly increased in the 500 and 1250ppm groups. The incidences of urothelial hyperplasia in the kidney pelvis were significantly increased in the 500, 1250 and 2500ppm groups. The present study documents the dose-response influence of diuron on the rat urothelium, with a no observed effect level (NOEL) at 125ppm; 1250ppm was as effective as 2500ppm at inducing urothelial lesions.

• Authors: Ana Paula Ferragut Cardoso, Shadia Muhammad Ihlaseh Catalano, Mitscheli Sanches da Rocha, Merielen Garcia Nascimento E Pontes, João Lauro Viana de Camargo, Maria Luiza Cotrim Sartor de Oliveira
• Journal: Toxicology (Toxicology) Vol. 312 Pg. 1-5 (Oct 04 2013) ISSN: 1879-3185 [Electronic] Ireland
• PMID: 23876856 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Herbicides
• Diuron

Topics

• Animals
• Diuron (toxicity)
• Dose-Response Relationship, Drug
• Herbicides (toxicity)
• Male
• Microscopy, Electron, Scanning
• Mucous Membrane (drug effects, pathology, ultrastructure)
• No-Observed-Adverse-Effect Level
• Rats
• Rats, Wistar
• Urothelium (drug effects, pathology, ultrastructure)