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  2. NTP Toxicology and Carcinogenesis Studies of Monuron (CAS No. 150-68-5) in F344/N Rats and B6C3F1 Mice (Feed Studies)

NTP Toxicology and Carcinogenesis Studies of Monuron (CAS No. 150-68-5) in F344/N Rats and B6C3F1 Mice (Feed Studies)

  • Natl Toxicol Program Tech Rep Ser. 1988 Aug;266:1-166.
National Toxicology Program
PMID: 12748686
Abstract

Carcinogenesis studies of monuron (greater than 99% pure), a substituted urea herbicide, were conducted by feeding diets containing 0, 750, or 1,500 ppm monuron to groups of 50 F344/N rats of each sex and 0, 5,000, or 10,000 ppm to groups of 50 B6C3F1 mice of each sex for 103 weeks. Survivors then were fed a control diet for 1 week, killed, and examined. Throughout most of the studies, mean body weights of dosed rats and mice of each sex were lower than those of the controls. Survival rates of low dose female rats and high dose male and female mice were increased relative to those of the controls. In 13-week toxicity studies, the lympho/hematopoietic system of rats and mice was the primary site affected. The lymphoid depletion found in these Animals was not seen in rats or mice surviving to the end of the 104-week studies. Nonneoplastic changes associated with the long-term administration of monuron to rats included renal tubular cell cytomegaly, mainly involving the proximal convoluted tubules in male and female rats, and dose-related hepatic cytoplasmic changes in male rats. In the 104-week study, the kidneys and liver of male rats were the primary tissues affected. Long-term administration of monuron was associated with an increase in renal tubular cell adenomas (control, 0/50; low dose, 2/50; high dose, 7/50) and renal tubular cell adenocarcinomas (0/50; 1/50; 8/50). Administration of monuron to male rats was associated with increased incidences of neoplastic nodules of the liver (1/50; 6/49; 7/50) and of neoplastic nodules or carcinomas (combined) of the liver (1/50; 6/49; 9/50). Dosed male and female rats had decreased incidences of mononuclear cell leukemia; dosed male rats had lower incidences of pheochromocytomas of the adrenal glands and C-cell carcinomas of the thyroid gland; dosed female rats had reduced incidences of mammary gland fibroadenomas. In male mice, dose-related decreases occurred in the incidences of hepatocellular carcinomas (6/50; 5/49; 2/50) and hepatocellular adenomas or carcinomas (12/50; 8/49; 6/50); incidences of hepatocellular tumors in low dose female mice were reduced in dosed female mice (16/50; 8/50; 7/50). Monuron was not mutagenic in Salmonella strains TA98, TA100, TA1535, or TA1537 in the presence or absence of Aroclor 1254-induced rat liver S9. Monuron did induce chromosomal aberrations and sister chromatid exchanges in cultured Chinese hamster ovary cells. The data, documents and pathology Materials from the 2-year studies of monuron have been audited. The audit findings show that the conduct of the studies is documented adequately and support the data and results given in this Technical Report. Under the conditions of these 2-year feed studies, there was clear evidence of carcinogenicity for male F344/N rats in that monuron caused increased incidences of tubular cell adenocarcinomas of the kidney, tubular cell adenomas of the kidney, and neoplastic nodules or carcinomas (combined) of the liver. Monuron induced cytomegaly of the renal tubular epithelial cells in both male and female F344/N rats. There was no evidence of carcinogenicity for female F344/N rats or for male or female B6C3F1 mice. Synonyms and Trade Names: N'-(4-chlorophenyl)-N,N-dimethylurea; 1,1-dimethyl-3-(p-chlorophenyl)urea; CMU; Karmex Monuron Herbicide; Telvar

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-B1875
    99.96%, Herbicide