The skin and eye primary irritation tests, and skin cumulative irritation test were performed on male rabbits, which were topically treated with a volume of 1 g/body of 0.06% and 0.12% dexamethasone valerate (DV-17) ointments as a test drug, and 0.1% hydrocortisone butyrate (HB) and 0.12% betamethasone valerate (BMV) ointments as an active control drug in order to evaluate the topical and systemic effects. No skin and eye primary irritations except minimal skin erythema and slight conjunctival redness were seen in above four corticosteroids. Judging from the results such as skin atrophy, inhibition of body weight gains, and decreases of thymus, spleen and adrenal weights, the potency of toxicities among the four corticosteroid ointments appeared to be as follows : 0.12% DV-17, 0.12% BMV > 0.1% HB> 0.06% DV-17.
The comparative toxicity test was performed on male rats, which were topically treated with a volume of 0.25 g/kg of 0.12% dexamethasone valerate (DV-17) ointment as a test drug, and 0.1% dexamethasone (DEX), 0.05% fluocinonide (FAA). 0.025% beclomethasone dipropionate (BMD), 0.1% hydrocortisone butyrate (HB), 0.05% clobetasol propionate (CP) and 0.12% betamethasone valerate (BMV) ointments as an active control drug for 30 consecutive days to evaluate on the effects of following items: body weight changes, adrenal functions (organ weight, histological changes of the cortex and serum contents of corticosterone), pathological changes of hypophysis and lymphatic systems (thymus, mesenteric lymph nodes and spleen), and skin changes. Furthermore, the recovery test was also carried out. The severity of topical toxicities was in parallel with that of systemic toxicities. Judging from the results obtained in this study, the potency of toxicities among seven corticosteroid ointments appeared to be as follows : FAA > DEX > CP> BMV, DV-17 > HB > BMD. The toxicities of DV-17 were comparable with that of BMV, and these side effects were found to be minimized on the recovery test.
Carcinogenicity study of cholestyramine, an anti-hyperchole-sterolemic agent, was carried out by feeding B6C3F1 mice of both sexes with the pellet diet in which cholestyramine was admixed at the rates of 1.25, 2.5 and 5%. The Animals were fed on the drug-admixed diet for 18 months and on a normal diet for subsequent 3 months. After 32 weeks the mortality of male mice began to increase in the 5% cholestyramine group and the number of dead or moribund mice increased markedly after 60 weeks. Hemorrhage recognized in pleural cavity, heart and other organs, was suggested to be the main cause of death. Some kinds of tumors occurred in each group, but the tumor-incidences seen in mice of 1.25 and 2.5% cholestyramine groups were similar to those in mice of the control group and the occurrence of the specific tumor or an acceleration of tumor-development by feeding cholestyramine were not observed. Furthermore, the tumor-incidence in mice fed on the 5% cholestyramine diet was less than that in mice of the other three groups.