title: Diuron exposure induces systemic and organ-specific toxicity following acute and sub-chronic exposure in male Wistar rats.
abstract: Diuron [3-(3,4-dichlorophenyl)-1,1-dimethylurea] is a substitute urea herbicide widely used on agricultural crops with potential mutagenic, teratogenic, reproductive and carcinogenic effects. Nonetheless, its toxic potential on the immune system needs a detailed assessment. Thus, in order to evaluate the adverse effect of this herbicide on lymphohematopoietic organs and macrophage activity, male Wistar rats were orally treated with Diuron at 125, 1250 and 2500 ppm for 14, 28 or 90 days. General signs of toxicity were observed in Diuron-treated groups (1250 and 2500 ppm), including reduced food intake and body weight gain, as well as higher relative weights for spleen, kidneys and liver (28 and 90-day toxicity studies) and elevated serum levels of ALT, albumin, total protein, creatinine and urea (28-day toxicity study). Diuron exposure caused a severe depletion of splenic white pulp compartments and cellularity, followed by a decreased number of CD4(+) T lymphocytes, increased extramedullary hematopoiesis and deposition of hemosiderin in red pulp. Despite alteration in macrophage spreading, the macrophagic activity was not significantly affected by the herbicide. Under these experimental conditions, the results suggest that Diuron exerts systemic and target-organ toxicity, mainly at higher concentration.
authors.affiliation: Department of Pathology, Botucatu Medical School, São Paulo State University - UNESP, Botucatu 18618-970, São Paulo, Brazil. domingues1@gmail.com
authors.forename: Alexandre
authors.initials: A
authors.lastname: Domingues
authors.forename: Luis Fernando
authors.initials: LF
authors.lastname: Barbisan
authors.forename: Priscila Raquel
authors.initials: PR
authors.lastname: Martins
authors.forename: Ana Lúcia Tozzi
authors.initials: AL
authors.lastname: Spinardi-Barbisan
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001853:Bone Marrow / Q000473:pathology; D004237:Diuron / Q000633:toxicity*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006413:Hematopoietic System / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D006861:Hydrogen Peroxide / Q000378:metabolism; D007107:Immune System / Q000187:drug effects; D008111:Liver Function Tests; D016131:Lymphocyte Subsets / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D009928:Organ Specificity; D016877:Oxidants / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D006540:Herbicides; D016877:Oxidants; D009569:Nitric Oxide; D004237:Diuron; D006861:Hydrogen Peroxide