The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Volume 12 , Issue SupplementI
Showing 1-2 articles out of 2 articles from the selected issue
  • Seiichi Imoto, Michiko Aoki, Kotaro Shimpo, Kazumasa Yamashita
    1987 Volume 12 Issue SupplementI Pages 1-33
    Published: February 28, 1987
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    A chronic oral toxicity test of proglumetacin maleate (PGM), an anti-inflammatory agent, was studied at dose-levels of 0, 0.6, 2.5 and 10.0 mg/kg/day using male and female beagle dogs. They were treated for 12 months, followed by 1 month recovery period. 1. Excretion soft and mucous feces was observed in females of 2.5 mg/kg/day group. In addition, excretion of diarrheal and blood-tinged feces was also found in females of 10.0 mg/kg/day group. 2. One female animal given 10.0 mg/kg/day of PGM was found dead on day 178 of administration. For about a month before death, diarrheal and blood-tinged feces, decreases in body weight and food consumption, and anemia had been noticed. At the autopsy, brown-cloudy ascitic fluid, adhesion of visceral organs, hyperemia or hemorrhage in the mucosa and serosa of the digestive tract, and an ulcer in the duodenum were found. 3. No significant influences of PGM were noted on the changes of body weights, food and water consumptions, excluding the dead animal. 4. A fecal occult blood test showed an increase in no. of animals with blood-positive reaction in 2.5 and 10.0 mg/kg/day groups of both sexes, especially marked in females of 10.0 mg/kg/day group. 5. In urinary tests, no significant changes were found in any of the PGM-treated groups of both sexes ; the dead one, however, showed decreases in urine volume and electrolyte excretion on month 6 of administration. 6. No significant hematological changes associated with the administration of PGM were found in any of the animals excluding the dead one, in which anemia and inflammation-related findings were found on month 6 of administration. 7. Serum-biochemical tests showed no significant changes in any of the PGM-treated groups of both sexes. 8. No significant influences of PGM wefe found on ICG and PSP clearances, ocular fundus and ECG. 9. At the autopsy performed at the end of administration, no significant changes were found in any of the PGM-treated groups of both sexes. 10. Histopathologically, a duodenal ulcer and peritonitis-related findings were observed in the female dead animal of 10.0 mg/kg/day group. 11. No influences of PGM were found in any of the tests performed at the end of the recovery phase. 12. From these results, the non-effective dose of PGM was estimated to be 0.6 mg/kg/day, and the toxic doses of PGM to be more than 10.0 mg/kg/day for males and 10.0 mg/kg/day for females, respectively, in beagle dogs treated orally with PGM for 12 months.
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  • Takashi HASEGAWA, Kazuo TAKAHASHI
    1987 Volume 12 Issue SupplementI Pages 35-47
    Published: February 28, 1987
    Released: February 21, 2008
    JOURNALS FREE ACCESS
    Antigenicity of terazosin was studied in the experimental animals and the following results were obtained. 1. Terazosin was shown to be non-immunogenic in guinea-pigs and mice when immunized alone or with mixture of terazosin and protein as immunogen. 2. Protein-conjugate of terazosin induced responses of hapten specific antibody when guinea pigs and mice were immunized. However, terazosin alone was shown to be not capable of eliciting any allergic responses. In conclusion, terazosin lacks immunogenicity and eliciting antigenicity in these experimental conditions and this suggests that drug allergic response would either not occur or be minimal, if any, when terazosin is administered clinically.
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