The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 10 , Issue SupplementII
Showing 1-6 articles out of 6 articles from the selected issue
  • Noboru HOSHI, Koichi UENO, Hiroko YANO, Kaoru HIRASHIMA, Haruo KITAGAW ...
    1985 Volume 10 Issue SupplementII Pages 129-146
    Published: October 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Extensive general pharmacological studies of hydroxypropylmethylcellulose acetate succinate (HPMCAS) were carried out in mice, rats, guinea pigs, rabbits, dogs and frogs. HPMCAS appeared to have no significant effect on the central nervous system, autonomic nervous system and cardiovascular system. Various biological analyses of the blood (including hemolysis and coagulation properties) and urine were unaffected, and the compound showed no significant local anesthetic or vascular permeability. At higher doses of HPMCAS, an increase in secretion of saliva in guinea pigs, a decrease in gastric juice secretion in rats and an increase in rectal temperature in rats were observed, but these effects did not show clear dose-dependence.
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  • Noboru Hoshi, Hiroko Yano, Kaoru Hirashima, Haruo Kitagawa, Yoshio Fuk ...
    1985 Volume 10 Issue SupplementII Pages 147-185
    Published: October 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    The acute toxicity (in rabbits and rats) and the subchronic and chronic toxicities (in rats) of Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a potentially useful pharmaceutical excipient, were investigated. 1) In the acute toxicity study (single oral dose of 2.5 g/kg), no deaths or behavioral abnormalities were observed. Thus, LD&lt50&gt is higher than 2.5 g/kg. 2) In the subchronic toxicity study (0.63, 1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 2 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in rats of both sexes, but the effect was not statistically significant. 3) In the chronic toxicity study (1.25 or 2.5 g/kg daily as a single oral dose in the morning, 6 days per week (not Sunday) for 6 months), no significant behavioral abnormality was observed. There was some decrease in body weight gain in male rats, but it was not statistically significant. 4) Various biochemical and physiological abnormalities in rats were noted in all groups (including the control groups) in the toxicity studies, but there appeared to be no significant dose-related finding attributable to the administration of HPMCAS.
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  • Noboru HOSHI, Koichi UENO, Takashi IGARASHI, Haruo KITAGAWA, Teruko FU ...
    1985 Volume 10 Issue SupplementII Pages 187-201
    Published: October 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A fertility study was carried out in Slc : SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1, 250 and 2, 500 mg/kg/day. Male rats were treated with HPMCAS from 60 days before pairing until the completion of mating. Female rats received HPMCAS for 22 days, from 14 days prior to mating up to Day 7 of gestation. All pregnant females were sacrificed on Day 21 of gestation and all fetuses were examined for abnormalities. No abnormal signs were seen in mating or fertility in the rat treated with HPMCAS. No external, internal and skeletal anomalies attributable to HPMCAS were observed in the fetuses. It was concluded that HPMCAS had no harmful effect on mating, fertilization, implantation, or embryonic development.
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  • Noboru HOSHI, Koichi UENO, Takashi IGARASHI, Haruo KITAGAWA, Teruko FU ...
    1985 Volume 10 Issue SupplementII Pages 203-226
    Published: October 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A teratogenicity study was carried out in S1c : SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1, 250 and 2, 500 mg/kg/day for a period of 11 days from day 7 to day 17 of gestation. Two-thirds of the pregnant females in each group were sacrificed on Day 21 of gestation and their fetuses were examined. The remaining dams were allowed to litter naturally, and the postnatal development of the offsprings was observed. The incidences of external, internal, and skeletal anomalies were not significantly increased in the fetuses of any treated groups. HPMCAS caused no effects on parturition, lactation, postnatal growth and reproductive ability of the male and female offspring.
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  • Noboru HOSHI, Koichi UENO, Takashi IGARASHI, Haruo KITAGAWA, Teruko FU ...
    1985 Volume 10 Issue SupplementII Pages 227-234
    Published: October 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A teratogical study was carried out in New Zealand White rabbits in order to examine the teratogenic potentiality of HPMCAS, a useful pharmaceutical excipient. HPMCAS was orally administered at dose levels of 625, 1, 250 and 2, 500 mg/kg/day for a period of 13 days from day 6 to day 18 of gestation. All pregnant females were sacrificed on day 29 of gestation and their fetuses were examined. The administration of HPMCAS during a period of organogenesis produced no embryotoxic and teratogenic effects as well as no influence on behavior, appearance and growth of animals.
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  • Noboru HOSHI, Koichi UENO, Takashi IGARASHI, Haruo KITAGAWA, Teruko FU ...
    1985 Volume 10 Issue SupplementII Pages 235-255
    Published: October 31, 1985
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A perinatal and postnatal study was carried out in Slc : SD rats orally administered Hydroxypropylmethylcellulose acetate succinate (HPMCAS), a useful pharmaceutical excipient, at dose levels of 625, 1, 250 and 2, 500 mg/kg/day for a period from day 17 of gestation to day 21 after delivery. All pregnant rats were allowed to litter naturally, and the postnatal develop-ment of the offsprings was observed. In the administered group of 2, 500 mg/kg, the liver weight was significantly increased in males and showed a tendency to increase in females as compared with control. No significant differences between the control group and the administered groups were found in postnatal growth and differentiation, behavior and reproductive ability of male and female offsprings.
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