The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 10 , Issue SupplementI
Showing 1-7 articles out of 7 articles from the selected issue
  • Masaya TAKEUCHI, Masayo KAGA, Tomoko TSUGA, Mizue ICHINOHE, Shuzo OKAZ ...
    1985 Volume 10 Issue SupplementI Pages 1-10
    Published: August 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Since halopredone acetate (THS-201), a synthetic corticosteroid, is expected to be used clinically for intra-articular injections because of its long-lasting activity in the synovial bursa, its acute toxicity was compared with that of triamsinolone acetonide (TA) and methylpredonisolone acetate (MPA). The test animals were Jcl : ICR mice and Jcl : Wistar rats, and drugs were administered orally, intraperitoneally and subcutaneously. The LD50 values of THS-201 both in mice and rats were estimated more than 5000 mg/kg at each route, and these are for above larger than those of TA or MPA. Moreover, in oral and subcutaneous administration of THS-201, no severe toxic signs were observed either in mice or in rats. In intraperitoneal injection, a few of mice and rats died after showing several clinical signs and suppression of body weight gain, and their autopsy revealed atrophy of thymus, spleen and adrenal, induction of infection and hemorrhage in digestive tract. On the other hand, the mice and rats administered TA or MPA revealed the severe toxic signs such as loss of hair gloss, marked emaciation, decrease in spontaneous movement, anemia, bloated face; decrease or suppression of body weight gain, atrophy of thymus, spleen and adrenal, severe induction of infection and lesions in digestive tracts. Accordingly, it is concluded that the acute toxicity of THS-201 in mice and rats was lower than that of TA or MPA.
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  • Masaya TAKEUCHI, Mizue ICHINOHE, Syuzo OKAZAKI, Miwako SATO, Masao KIG ...
    1985 Volume 10 Issue SupplementI Pages 11-39
    Published: August 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Halopredone acetate (THS-201), a synthetic corticosteroid, is expected to be used clinically for intra-articular injection because of its long-lasting activity in the synovial bursa. Subacute toxicity study was carried out on THS-201 by using Jcl: Wistar rats. THS-201 was subcutaneously admin-istered to the rat in doses of 0.1, 0.5, 2.5 and 12.5 mg/kg/day, with the periods for administration and recovery being 3 and 2 months, respectively. Methyl-predonisolone acetate (MPA) was used for the positive control in dose of 0.5 mg/kg/day. In the group of THS-201 12.5 mg/kg, the below findings were observed: thinning of lumbar hair, swelling of injection site, suppression in body weight gain and decrease of food consumption. The lesions to lymphatic system were indicated by the examinations of peripheral blood, autopsy and histopathology. Slight changes in erythrocytic and biochemical values were seen, and foreign body granuloma was observed in injected subcutis. These findings, exception for lesion of injection site, were almost recovered after the 2 month-recovery period. In the group of THS-201 2.5 mg/kg, some of the changes were noted slightly. In the groups of THS-201 0.5 and 0.1 mg/kg, any toxic changes attributable to THS-201 were not observed. On the other hand, in the group of MPA 0.5 mg/kg, similar findings noted in THS-201 12.5 mg/kg group were observed, but these changes were recovered almost completely at the end of the 2 month-recovery period. It was concluded that the non-toxic does and the defined toxic does of THS-201 in this study were 0.5 and 2.5 mg/kg/day, respectively.
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  • Masaya TAKEUCHI, Mizue ICHINOHE, Shuzo OKAZAKI, Yuko OHTA, Kotaro SHIM ...
    1985 Volume 10 Issue SupplementI Pages 41-69
    Published: August 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Chronic toxicity study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl : Wistar rats. THS-201 was subcutaneously administered to the rat in doses of 0.02, 0.1, 0.5 and 2.5mg/kg/day, with the periods for administration and recovery being 12 and 2 months, respectively. In the group of THS-201 2.5 mg/kg, the below findings were observed :thinning of lumbar hair, suppression in body weight gain, decrease of food consumption in both sexes and decrease of water consumption in male. The lesions to lymphatic system were indicated by the examinations of hemogram, organ weight and histopathology. A few changes in urinary and biochemical values were seen, and foreign body granuloma was observed in the injected subcutis. After 2 month-recovery period, above-mentioned findings almost disappeared. In the group of THS-201 0.5mg/kg, some of the changes were noted slightly and disappeared after the recovery period. IN the groups of THS-201 0.1 and 0.02mg/kg, any toxic changes attrib-utable to THS-201 were not observed. It was concluded that the non-toxic does and the defined toxic dose of THS-201 in this study were 0.1 and 0.5 mg/kg/day, respectively.
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  • Seiichi IMOTO, Akiko YAHATA, Megumi KOSAKA, Satoru KAMADA, Masaya TAKE ...
    1985 Volume 10 Issue SupplementI Pages 71-81
    Published: August 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A fertility study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl: Wistar rats. Male rats were treated subcutaneously for 63 days before mating and throughout mating, and female rats were treated subcutaneously for 14 days before mating and until day 7 of gestation, in doses of 0.04, 0.2, 1.0 and 5.0 mg/kg/day. Male and female rats in the same dose were mated. All of the pregnant rats were killed on day 20 of gestation and their fetuses were examined morphologically. The results obtained from the present study were as follows. A decrease in body weight gain was observed in male rats of 1.0 and 5.0 mg/kg groups, compared to the vehicle control group. In female rats of 5.0 mg/kg group, a decrease in body weight gain during gestation period was observed. However, no influences attributable to THS-201 administration were observed on the fertility and fetal development. These results indicated that the non-effect dose of THS-201 for the fertility of rats and fetal development was 5.0 mg/kg/day.
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  • Seiichi IMOTO, Satoru KAMADA, Akiko YAHATA, Megumi KOSAKA, Masaya TAKE ...
    1985 Volume 10 Issue SupplementI Pages 83-103
    Published: August 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A teratogenicity study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jc1 : Wistar rats. Pregnant rats were treated subcutaneously in doses of 0.1, 0.5, 2.5 and 12.5mg/kg/day, from day 7 to day 17 of gestation. Two-thirds of pregnant rats were killed on day 20 of gestation to examine the development of fetuses, and remaining rats were allowed to litter naturally in order to investigate the postnatal development of offspring. The results obtained from the present study were as follows. During the gestation and lactation periods, there occurred a decrease in the maternal body weight gain in 2.5 and 12.5 mg/kg groups. No influences of THS-201 administration were observed on gestation, delivery and lactation of dams. No external, visceral and skeletal anomalies attributable to THS-201 were observed in the fetuses. THS-201 administration did not have any influe-nces on viability and development, various functions such as reflex response, learning and reproductive performance of F1 generation, and further on development of F2 generation. Therefore, it was concluded that the non-effect does of THS-201 for the reproduction of dams and development of F1 generation was 12.5 mg/kg/day.
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  • Seiichi IMOTO, Akiko YAHATA, Megumi KOSAKA, Satoru KAMADA, Masaya TAKE ...
    1985 Volume 10 Issue SupplementI Pages 105-122
    Published: August 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A peri-and postnatal study of halopredone acetate (THS-201), a synthetic corticosteroid, was carried out using Jcl: Wistar rats. Pregnant rats were treated subcutaneously in doses of 0.05, 0.4, 3.2 and 25.6 mg/kg/day, from day 17 of gestation to day 21 after delivery. All pregnant rats were allowed to litter naturally, and the postnatal development of offsprings was observed. The results obtained from the present study were as follows. No influences of THS-20l administration were observed on gestation, delivery and lactation of dams. THS-201 administration did not have any influences on viability and development, various functions such as reflex response, learning and reproductive performance of Fl generation, and further on development of F2 generation. Therefore, it was concluded that the non-effect dose of THS-201 for the reproduction of dams and development of Fl generation was 25.6 mg/kg/day.
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  • Akinobu OHUCHIDA, Ryoichi YOSHIDA, Ken'ichi MORITA
    1985 Volume 10 Issue SupplementI Pages 123-128
    Published: August 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The mutagenicity of halopredone acetate (THS-201) was investigated by means of reverse mutation test in seven bacterial strains (S. typhimurium TA100, TA1535, TA98, TA1538, TA1537 and E. coli WP2, WP2 uvrA) and chromosomal aberration test in cultured Chinese hamster cells (CHL). In the reverse mutation test, no significant increase of revertant was observed at dose levels from 50 to 5000 μg/plate in the absence and presence of mammalian metabolic activation system. THS-201 caused no increase of chromosomal aberrants at dose levels of 1.6, 8.0, 40.0 and 200 μg/ml irrespective of metabolic activation. These results indicated that THS-201 has no mutagenic activity.
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