The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 11 , Issue SupplementII
Showing 1-8 articles out of 8 articles from the selected issue
  • Ryouichi YOSHIDA, Osamu YAMAKITA, Mitsuhiro SHINOMIYA, Ken'ichi MORITA
    1986 Volume 11 Issue SupplementII Pages 1-9
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    An acute toxicity of NT-1 tape was investigated in mice, rats and rabbits, and also an acute toxicity of NT-1 ointment in rabbits. An irritation of NT-1 tape was investigated in rabbits. 1. Dead animals treated with NT-1 tape or ointment were not observed in reliable maximum administration dose of 0.88 mg/body as GTN (nitroglycerin) in mice (male ; about 29.1 mg/kg, female ; about 35.2 mg/kg), of 3.96 mg/body as GTN in rats (male ; about 26.0 mg/kg, female ; about 28.9 mg/kg) and of 480 mg/kg as GTN in rabbits. 2. There were not toxic signs in mice and rats. The below findings were observed in rabbits treated mainly with NT-1 ointment: decreased spontaneous activity, decreased reactivity to various stimuli such as sound and touch, and behavior of binding food box. However, the rabbits recovered from those abnormal behavior in a day. 3. Any body weight changes and any autopsy findings attributable to NT-1 tape or ointment were not observed in mice, rats and rabbits. 4. The effects on ECG were not observed in rabbits. 5. The GTN absorption ratio in rabbits treated with NT-1 ointment was thought to be 60-70% from GTN residual ratio. 6. The skin irritation was not observed in rabbits treated with NT-1 tape.
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  • Yuzo TANIGUCHI, Kaoru SHIMADA, Hachiro KOHYAMA, Yoshinori HAMAI, Ryuic ...
    1986 Volume 11 Issue SupplementII Pages 11-29
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    NT-1 ointment is a compound containing 10% nitroglycerin which is topically applied to the skin for angina pectoris. The subacute toxicity of this compound was examined by the continuous application for 5 weeks to the shaven skin of rabbit back at dose levels of 240, 120 and 60 mg/kg, and the recovery was examined 3 weeks after withdrawal of the drug. No special skin response to the NT-1 ointment was observed other than an erythema of the grading 2-3 Draize points, while the control ointment, which was the base ointment without nitroglycerin, showed a higher grade of erythema equivalent to 4 Draize point with crusta formation. No relationship between the dose level of NT-1 ointment and the skin response was observed, and skin response was thought to be caused mainly by the base ointment. The skin response gradually reduced even during the application period, and the skin response disappeared within a few days after withdrawal of the ointment. Histological examination of the treated skin at the respective ends of the application and recovery periods showed thickening of the corneum and epithelial layer, round cell infiltration and fibrosis in the corium, and development of hair folliculi in the subdermis. No systemic effect of the topically applied NT-1 ointment was observed in the majority of the animals, either in behavior, hematologic and electrocardiographic examination, food consumption, body weight change or urinalysis.
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  • Seiichi IMOTO, Miyuki KURAMOTO, Kotomi IWABUCHI, Hiroshi NAGAI, Kotaro ...
    1986 Volume 11 Issue SupplementII Pages 31-57
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A chronic toxicity test of 10% nitroglycerin (NT-1 ointment) was carried out in male NZW rabbits. NT-1 ointment was applied to the back skin for 26 weeks at daily doses of 15, 60 and 240 mg/kg as nitroglycerin itself, and 5-week withdrawal period was followed. 1. Topical dermal responses to NT-1 : Macroscopically, erythema, edema, scales, papu1es and dermal thickening were observed in response to NT-1 ointment. In the withdrawal period, however, all of them disappeared. Histopathologically, thickening of epidermis and cell infiltration were observed in response to NT-1 ointment. In addition, elongation of rete ridges and Touton giant cells were found only in 60 and 240 mg/kg groups, and hyperkeratosis only in 240 mg/kg group. At the end of withdrawal period, Touton giant cells were still found in 60 and 240 mg/kg groups, although the other dermal reactions disappeared. 2. Systemic responses to NT-1 ointment: A slight increase in the excretion of loose or mucous feces was observed in 240 mg/kg :group. The weights of right and left kidneys were increased by the administration of 240 mg/kg NT-1 ointment, and a similar trend was seen also in the weight of heart, although there found no such among-group differences at the end of withdrawal period. White blood cells, especially neurtophils, and γ-globulin fraction were increased in response to 240 mg/kg NT- 1 ointment. 3. In conclusion, a no-toxic effect dose of NT-1 ointment as nitroglycerin itself was considered to be 15 mg/kg/day for the skin and 60 mg/kg/day for the general somatic system.
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  • Seiichi IMOTO, Masumi NAKAO, Miyuki KURAMOTO, Masaya TAKEUCHI, Kotaro ...
    1986 Volume 11 Issue SupplementII Pages 59-70
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A teratological test of 10% nitroglycerin (NT-1 ointment) was carried out in New Zealand White rabbits. Pregnant rabbits were treated percutaneously with NT-1 ointment from day 6 to 18 of gestation at dose levels of 15, 60 and 240 mg/kg/day as nitroglycerin itself. All pregnant rabbits were killed on day 29 of gestation, and the influences of NT-1 ointment upon the performances of dams and fetuses were examined. During the treatment period, erythema was observed on the treated dorsal skin in all groups excluding the nontreatment control group. However, it disappeared soon after the cessation of NT-1 ointment administration. Influences of NT-1 ointment administration were not found at any dose levels on the food consumption and body weight changes of pregnant rabbits. In addition, influences of NT-1 ointment on the reproductive performance of dams and the development of fetuses were not observed at any dose levels. Therefore, the non-effect dose of NT-1 ointment on reproductive performance of dams and fetal development in rabbits was estimated to be 240 mg/kg/day and more as nitroglycerin itself.
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  • Osamu YAMAKITA, Ryouichi YOSHIDA, Mitsuhiro SHINOMIYA, Masahiro KOIDA, ...
    1986 Volume 11 Issue SupplementII Pages 71-80
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Teratogenicity of 1, 1, 3-trimethyl-5-phenylbiuret (ST-281), a new anti-rheumatic agent, was evaluated in rabbits. ST-281 at doses of 0, 50, 100, 200 and 400 mg/kg/day were administered orally to pregnant NZW rabbits from day 6 to day 18 of pregnancy. Body weight and food consumption at the administration and the subsequent periods were significantly decreased in 400 mg/kg/day group, and 5 dams (41.7%) affected severely were dead. No remarkable changes were investigated in findings at near-term caesarean section in any dosed group including 400 mg/kg/day. In visceral and skeletal examinations, no significant increase in incidence of abnormal fetuses were observed. This report suggests that ST-281 has no embryotoxicity or teratogenicity in rabbits.
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  • Kazumasa YAMASHITA, Hideaki YADA, Kenji IRIMURA, Taiji HAYASHI, Hideno ...
    1986 Volume 11 Issue SupplementII Pages 81-106
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    In order to evaluate the long-term-safety of halopredone acetate (THS-201: 17α, 21-diacetoxy-2-bromo-6β, 9α-difluoro-11β-hydroxy-1, 4-pregnadiene-3, 20-dione), a 52-week chronic toxicity study was performed on the basis of its local accumulation in dogs. In doses of 0.1, 0.5 and 2.5 mg/kg, THS-201 was injected into the right knee joint in both sexes of dogs every 2 weeks for 39 weeks and withdrawn for 13 weeks. In this study, the below slight local changes were observed in both sexes of dogs treated with 2.5 mg/kg/2 weeks of THS-201 : focal loss of hair of the injection site, lesser stain in cartilage matrix of articular cartilage and meniscus in light microscopic examinations, and irregular thickness and elongation of collagen fibers, roughness of fibrous density and decrement of proteoglycans in electron microscopic examinations. In, conclusion, systemic adverse effects were not observed in any dogs treated with THS-201.
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  • Shin-ichiro NINOMIYA, Kazuya HASHIMOTO, Nobuyuki TANAKA
    1986 Volume 11 Issue SupplementII Pages 107-119
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The oral acute toxicity studies of SF-1008C, an elemental diet for hepatic failure, and its components (peptide and rice oil) were evaluated in ICR mice and Sprague-Dawley rats. The following results were obtained. 1. Mortality: The minimum lethal doses for SF-1008C in male and female mice and rats were higher than 40 g/kg. The minimum lethal doses for peptide in male and female mice and rats were higher than 6 g/kg. The minimum lethal doses for rice oil in male and female mice and rats were higher than 20 m1/kg. 2. General symptoms: The major signs observed were loose stool in the mice treated with SF-1008C, yellowish brown urine in the rats treated with SF-1008C or peptide and diarrhea in the rats treated with rice oil. 3. Body weight and food consumption: Decrease in food consumption and slight decrease in body weight gain were observed in the female mice treated with SF-1008C, peptide and rice oil, but the decrease was not dose-dependent. Decrease in food consumption was also observed in the male and female rats treated with of SF-1008C and rice oil, but the decrease was not dose-dependent. Body weight, however, did not show significant change in any group of rats. 4. Gross pathlogy: No drug-related changes in organs and tissues were observed by necropsy in any group of mice or rats. Based on these results, the acute toxicities of SF-1008C and its components were low, respectively.
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  • Shuzo OKAZAKI, Mizue ICHINOHE, Yuko OHTA, Masaya TAKEUCHI, Kotaro SHIM ...
    1986 Volume 11 Issue SupplementII Pages 121-142
    Published: May 01, 1986
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The toxicity of an elemental diet (SF-1008C) for hepatic failure and recovery after administration were investigated in Sprague-Dawley rats. The rats were orally administered the drug in doses of 10, 20 and 30 g/kg/day for five weeks, after which, recovery was studied for five weeks. The results were summarized as below: In the 30g/kg/day group, decreases in food and water consumption were observed, while the body weight gain and the rate of body weight gain were high compared to the treated control group. In addition, urinary pH and serum total protein were lower, and serum glucose and calcium levels were higher than in the treated control group, but these results were not considered to be due to the drug's toxicity. In the 20 and 10 g/kg/day groups, a slight decrease in food consumption was observed, though the rate of body weight gain was higher than in the treated control group. Slight decreases in urinary pH and serum total protein were observed, but were not considered to be due to the toxic effect of the drug. From the above results, it was concluded that the maximal non-effect dose of SF-1008C in oral administration was 30 g/kg/day, which was the maximally applicable dose in rats.
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