| Non-Human Toxicity Excerpts | /LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ ... 5,5-Dimethylhydantoin (DMH) in Rats, Dantoin (DMH, purity = 99.8%) was fed in diet to CD rats (60/sex/dose) at 0 (2 control groups), 100, 300, or 1000 mg/kg/day for 104 weeks. Diets were adjusted periodically for DMH concentration to maintain the doses with separate diets for males and females. Chronic NOEL = 300 mg/kg/day (Survival time relative to controls was decreased in both sexes at 1000 mg/kg/day, however it was statistically significantly decreased only in males. Bodyweights were statistically significantly lower (9 - 14%) in females at 1000 mg/kg late in the study. Bodyweight gains were significantly decreased (compared to both controls) in males at 1000 mg/kg. No effects were observed in relation to hematology, clinical chemistry, urinalysis, ophthalmology, organ weights or pathology.) Oncogenic NOEL > 1000 mg/kg/day (There were no treatment-related tumorigenic effects at any dose.) /5,5-Dimethylhydantoin//LABORATORY ANIMALS: Chronic Exposure or Carcinogenicity/ Dimethylhydantoin (purity = 98.9%) was fed in diet to Beagle dogs (4/sex/dose) at 0, 4000, 12000 and 40000 ppm for one-year. Chronic NOEL = 12000 ppm (Adrenal cortical hypertrophy was increased and correlated with increased relative adrenal weight for males at 40000 ppm. Adrenal hypertrophy was diffuse/bilateral and involved zona fasciculata cells. Body weight values were not statistically significantly decreased, but were generally lower in both sexes at 40000 ppm relative to the controls.) NOEL = 12000 ppm. /5,5-dimethylhydantoin//LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ Dimethylhydantoin (96.0 - 98.7% pure) was administered orally by gavage to Crl:CD BR rats (30/sex/dose/generation) at 0 (1% methylcellulose), 250, 500 or 1000 mg/kg/day (limit test) from 70 days pre-mating through lactation (21 days post-natal) for 2 generations (F0 & F1). Reproductive NOEL > 1000 mg/kg/day (No treatment-related effects at any dose.) Pup NOEL = 250 mg/kg/day (F1 pups had significantly decreased body weights at > 500 mg/kg and F2 pups at 1000 mg/kg. F2 mean live litter size was significantly decreased at 1000 mg/kg prior to culling.) Male Parental NOEL = 250 mg/kg/day (F1 weanling mean male body weights were decreased at the start of the F1 generation. They were decreased 9-10% weeks 19 and 20 at > 500 mg/kg and remained slightly decreased through week 37. These decreases were very slight, however (< 10%). Absolute and relative kidney (F0) and pituitary (F1) weights were increased in males at 1000 mg/kg.) Female Parental NOEL >1000 mg/kg/day (No treatment-related effects were observed at any dose.) /5,5-dimethylhydantoin//LABORATORY ANIMALS: Developmental or Reproductive Toxicity/ 5,5-Dimethylhydantoin (97%) was administered by gavage to groups of 27 mated New Zealand White Rabbits at dose levels of 0, 1.0, 100 or 1050 mg/kg/day in vehicle - water on days 7 - 19 of gestation. Possible increases in abortion rate and increased incidence of clinical signs at 1050 mg/kg/day, however not statistically significant. No evidence of toxicity in any fetal parameter measured. Maternal NOEL = Developmental NOEL = 1050 mg/kg/day. /5,5-dimethylhydantoin//GENOTOXICITY/ Chromosome aberration assay in Chinese hamster ovary cells using 5,5-Dimethylhydantoin, 97%0, 100, 200, 500, 1000 or 2000 ug/mL with and without Aroclor-induced rat liver S-9 activation. Only top four doses were analyzed. No significant increase in numerical or structural chromosome aberrations were observed. /5,5-dimethylhydantoin/ |
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