TY - JOUR
T1 - Diuron-induced rat urinary bladder carcinogenesis
T2 - Mode of action and human relevance evaluations using the international programme on chemical safety framework
AU - Da Rocha, Mitscheli Sanches
AU - Arnold, Lora L.
AU - De Oliveira, Maria Luiza Cotrim Sartor
AU - Catalano, Shadia M.Ihlaseh
AU - Cardoso, Ana Paula Ferragut
AU - Pontes, Merielen G.N.
AU - Ferrucio, Bianca
AU - Dodmane, Puttappa R.
AU - Cohen, Samuel M.
AU - De Camargo, João Lauro V.
N1 - Funding Information:
The employment affiliation of the authors is shown on the cover pages. All of the authors were associated with academic institutions when the paper was prepared. One of the authors (Shadia M. Ihlaseh Catalano) has subsequently become an employee of BASF, an international firm that manufactures and markets herbicides. Research funds were provided by the Funda ç ã o de Amparo à Pesquisa do Estado de S ã o Paulo (FAPESP, Grants 2006/60506-1, 2009/02754-7), Conselho Nacional de Pesquisa (CNPq, 472330/07-1), Center for Evaluation of The Impact of the Environment on Human Health (TOXICAM), UNESP, and University of Nebraska Medical Center. The Coordenadoria para Aperfei oamento de Pessoal de Ensino Superior (CAPES), Brazilian Ministry of Education (MEC), provided a scholarship to Dr. Da Rocha for a training period at the University of Nebraska Medical Center (UNMC) during her PhD program. FAPESP provided fellowships to Shadia M. I. Catalano and Merielen G. N. Pontes, and the CAPES to Ana Paula F. Cardoso for their PhD programs. None of the authors have appeared before regulatory agencies or participated in legal proceedings concerned with the safety of diuron. The research findings reported, the preparation of the review, and the conclusions drawn are exclusively the academic work product of the authors and do not necessarily represent the views of the organizations that provided financial support or the authors’ employers. The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
PY - 2014/5
Y1 - 2014/5
N2 - 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.
AB - 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.
KW - Bladder cancer
KW - Cell proliferation
KW - Cytotoxicity
KW - Diuron
KW - Hyperplasia
KW - Metabolites
KW - Urothelium
UR - http://www.scopus.com/inward/record.url?scp=84899533878&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899533878&partnerID=8YFLogxK
U2 - 10.3109/10408444.2013.877870
DO - 10.3109/10408444.2013.877870
M3 - Review article
C2 - 24512549
AN - SCOPUS:84899533878
SN - 1040-8444
VL - 44
SP - 393
EP - 406
JO - Critical reviews in toxicology
JF - Critical reviews in toxicology
IS - 5
ER -