National Toxicology Program technical report series
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Natl Toxicol Program Tech Rep Ser · Dec 1993
NTP Toxicology and Carcinogenesis Studies of Triamterene (CAS No. 396-01-0) in F344/N Rats and B6C3F1 Mice (Feed Studies).
Triamterene is a potassium-sparing diuretic used in the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and other diseases in which edema may occur. Toxicity and carcinogenicity studies were conducted by administering triamterene (greater than 99% pure) in feed to groups of male and female F344/N rats and B6C3F1 mice for 15 days, 13 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 15-day Studies: Groups of five male and five female rats were fed diets containing 0, 1,000, 3,000, 10,000, 30,000, or 60,000 ppm triamterene. ⋯ Exposure to triamterene was associated with an increased incidence of hepatocellular foci, primarily mixed cell type, and an increase in the severity of nephropathy in female rats. In mice, exposure to triamterene was associated with an increased incidence of hepatocellular foci in females and an increased incidence of thyroid gland follicular cell hyperplasia in males and females. Synonyms: 6-Phenyl-2,4,7-pteridinetnamine; 6-phenyl-2,4,7-triaminopteridine; 2,4,7-triamino-6-phenypteridine; ademin; pterofen; pterophane; NSC-77625; SKF 8542 Trade names: Dyrenium, Dyazide, Dyren, Dytac, Jatropur, Maxzide, Noridyl, Triteren, Teriam, Urocaudal
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Natl Toxicol Program Tech Rep Ser · Dec 1993
NTP Toxicology and Carcinogenesis Studies of Promethazine Hydrochloride (CAS No. 58-33-3) in F344/N Rats and B6C3F1 Mice (Gavage Studies).
Promethazine hydrochloride is a drug used for the management of allergic conditions, motion sickness and nausea, and as a sedative to (treat psychiatric disorders. This drug was nominated for testing by the Food and Drug Administration because of its widespread use in human medicine and because of lack of data on its potential carcinogenicity. Oral administration is the most common route of human exposure. ⋯ The decrease in the incidences of adrenal medullary pheochromocytoma in male rats was considered to be related to promethazine hydrochloride administration. The decrease in the incidences of pituitary gland adenoma in male rats and uterine stromal polyp in female rats may have been related to promethazine administration. Synonyms: Phenothiazine,10-(2-(dimethylamino)propyl)-,monochlorohydrate; 10H-phenothiazine-10-ethanamine;10-(2-dimethylamino-2-methylethyl)phenothiazine hydrochloride; N-(2 -dimethylamino-2 -methyl)ethylphenothiazine hydrochloride Trade names: Diprazi; Kinetosin; Phenergan; Phenergan hydrochloride; Promine; Pipolfen; Plletia; Prorex; Promantine; Pyrethia; Romergan hydrochlonde
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Natl Toxicol Program Tech Rep Ser · Nov 1993
Toxicology and Carcinogenesis Studies of 5,5-Diphenylhydantoin (CAS No. 57-41-0) (Phenytoin) in F344/N Rats and B6C3F1 Mice (Feed Studies).
5,5-Diphenylhydantoin and its sodium salt are primarily used in the treatment of grand mal and psychomotor seizures, often in combination with other anticonvulsants, including phenobarbital. 5,5-Diphenylhydantoin is a suspected human carcinogen and was one of three compounds selected by the NTP to investigate the potential value of perinatal exposures in assessing chemical carcinogenicity. Chronic toxicity and carcinogenicity studies of 5,5-diphenylhydantoin were conducted in male and female F344/N rats and B6C3F1 mice. The studies were designed to determine the following: a) the effects of 5,5-diphenylhydantoin in the diet given to rats and mice during the adult (F1) period only (a typical carcinogenicity study), b) the toxic and carcinogenic effects of 5,5-diphenylhydantoin in rats and mice receiving perinatal (F0) exposure only (dietary exposure of dams prior to breeding and throughout gestation and lactation), and c) the effects of combined perinatal and adult exposure to 5,5-diphenylhydantoin. ⋯ Combined Perinatal and Adult Exposure: Combined perinatal and adult dietary exposure to 5,5-diphenylhydantoin confirmed the findings of the increased incidences of hepatocellular neoplasms for adult-only exposures in male F344/N rats and female B6C3F1 mice, although combined exposure did not enhance these neoplastic effects. However, in male B6C3F1 mice, combined perinatal and adult exposure resulted in increased incidences of hepatocellular neoplasms (hepatocellular carcinomas and multiple adenomas) that were not seen when dietary exposure was limited to the adult exposure period only. Synonyms: Diphenylhydantoin; 5,5-diphenyl-2,4-imidazolidinedione Trade names: Difhydan; Dihycon; Di-Hydan; Di-Lan; Dilabid; Dilantin; Ekko; Hydantol; Lehydan; Zentropil
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Natl Toxicol Program Tech Rep Ser · Sep 1993
NTP Toxicology and Carcinogenesis Studies of 3,4-Dihydrocoumarin (CAS No. 119-84-6) in F344/N Rats and B6C3F1 Mice (Gavage Studies).
3,4-Dihydrocoumarin was nominated by the Food and Drug Administration and the National Cancer Institute for study because of its widespread use as a flavoring agent in beverages, gelatins, puddings, candy, and other food items; as a fragrance in perfumes, creams, and cosmetics; and because of interest in the structure-activity relationships of the coumarin derivatives. Toxicity and carcinogenicity studies were conducted by administering 3,4-dihydrocoumarin (99% pure) in corn oil by gavage to groups of male and female F344/N rats and B6C3F1 mice for 16 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, and peripheral blood cells of mice. 16-DAY STUDY IN RATS: Groups of five male and five female rats received 3,4-dihydrocoumarin in corn oil by gavage at doses of 0, 190, 375, 750, 1,500, or 3,000 mg/kg body weight 5 days per week for a total of 12 doses in a 16-day period. ⋯ There was no evidence of carcinogenic activity of 3,4-dihydrocoumarin in male B6C3F1 mice receiving 200, 400, or 800 mg/kg. There was some evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of hepatocellular adenoma and hepatocellular adenoma or carcinoma (combined). 3,4-Dihydrocoumarin caused ulcers, hyperplasia, and inflammation of the forestomach, parathyroid gland hyperplasia, and increased severity of nephropathy in male rats. Synonyms: 1,2-benzodihydropyrone, 2H-1-benzopyran-2-one, 2-chromanone, 3,4-dihydro-2H-1-benzopyran-2-one, dihydrocoumarin, hydrocoumarin, o-hydroycinnamic acid, delta-lactone-hydrocinnamic acid, melilotin, melilotine, melilotol, 2-oxochroman
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Natl Toxicol Program Tech Rep Ser · Sep 1993
NTP Toxicology and Carcinogenesis Studies of Benzyl Acetate (CAS No. 140-11-4) in F344/N Rats and B6C3F1 Mice Feed Studies).
Benzyl acetate is used as a flavoring agent in foods, as a fragrance in soaps and perfumes, as a solvent for cellulose acetate and nitrate, and as a component of printing inks and varnish removers. The NTP previously studied the toxicology and carcinogenicity of this chemical in F344/N rats and B6C3F1 mice using the gavage route of administration and corn oil as a vehicle. Benzyl acetate increased the incidences of pancreatic acinar cell adenomas in male rats and the incidences of hepatocellular adenomas and forestomach neoplasms in male and female mice. ⋯ There was no evidence of carcinogenic activity in female F344/N rats receiving 250 or 500 mg/kg a day. There was some evidence of carcinogenic activity in male and female B6C3F1 mice, indicated by the increased incidences of hepatocellular adenomas and squamous cell neoplasms of the forestomach. Synonyms: acetic acid benzyl ester, acetic acid phenyl methyl ester, (acetoxymethyl)benzene, acetoxytoluene, benzyl ethanoate, phenylmethyl acetate