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Time course changes in cell proliferative activity of thyroid focal hyperplastic and tumorous lesions as well as blood thyroid-related hormones in male F344 rats initiated with N-bis(2-hydroxypropyl)nitrosamine (DHPN: 2800 mg/kg body weight, single s.c. injection) were examined following chronic administration of 0.1% sulfadimethoxine (SM) in the drinking(More)
To examine toxicities of nitrobenzene as part of the re-evaluation of toxicities of existing chemicals, a 28-day repeat dose toxicity study was performed in male and female F344 rats at dosages of 0, 5, 25 and 125 mg/kg/day of nitrobenzene. All rats in each group consisting of 6 males and 6 females received a daily intragastric administration of this(More)
The present studies were performed to investigate the possible mechanism of marked species differences on nephropathy found in the long-term toxicity study of FYX-051, a xanthine oxidoreductase inhibitor. In the twenty-six-week dose toxicity study in the rat, in which FYX-051 was administered by oral gavage at 0.04, 0.2, and 1 mg/kg, xanthine-mediated(More)
The testicular toxicity of cyclophosphamide (Cp) in rats was evaluated by quantitative morphometry of spermatogenic cycle stages. Nine-week-old male Sprague-Dawley rats in Group 1 were given a single oral administration of 100 mg/kg of Cp, and were sacrificed at 1, 7, 14 and 21 days thereafter. Rats in Group 2 were orally given 100 mg/kg/day of Cp for 2(More)
The possible mechanism of the underlying nephropathy found in the rat toxicity study of FYX-051, a xanthine oxidoreductase inhibitor, was investigated. Rats received oral treatment of either 1 or 3 mg/kg of FYX-051, with and without citrate for four weeks to elucidate whether nephropathy could be caused by materials deposited in the kidney. Furthermore,(More)
To clarify the toxicological aspects of FYX-051, a xanthine oxidoreductase inhibitor, which is currently being developed as a therapeutic agent against gout and hyperuricemia, we performed the study focused on species differences in FYX-051-induced nephropathy. In the repeated toxicology testing by oral administration, nephropathy was seen at 1 mg/kg and(More)
As a precedent study for elucidating the mechanism of possible urinary bladder carcinogenesis due to xanthine crystals induced by FYX-051, a xanthine oxidoreductase inhibitor, we have determined the experimental conditions suitable for the 52-week simultaneous treatment with citrate in F344 rats. Simultaneous treatment with citrate and FYX-051 produced both(More)
To determine a rat strain appropriate for carcinogenicity testing of FYX-051, a xanthine oxidoreductase inhibitor, we performed a 4-week oral toxicity study by administering 0.3, 1 and 3 mg/kg, and 1, 3 and 10 mg/kg of FYX-051 to male Sprague-Dawley (SD) and Fischer (F344) rats, respectively. Histopathology revealed that the degree of FYX-051-induced(More)
A chronic toxicity and carcinogenicity study, in which male and female F344/DuCrj rats were given potassium iodide (KI) in the drinking water at concentrations of 0, 10, 100 or 1000 ppm for 104 weeks, and a two-stage carcinogenicity study of application at 0 or 1000 ppm for 83 weeks following a single injection of N-bis(2-hydroxypropyl)nitrosamine (DHPN),(More)
To investigate the mechanism on photosensitive dermatitis caused by ketoprofen (KP) in humans, the following experiments were performed by topical application on guinea pigs. The phototoxicity study involving treatment with 10% solution of KP, its enantiomers (R-KP and S-KP), loxoprofen, and flurbiprofen revealed no phototoxic reactions. In the(More)