Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Teratogenicity Study of KTC-1, a New Semisynthetic Rifamycin Derivative, in Rats

새로운 반합성 Rifamycin 유도체 KTC-1의 랫트 최기형 시험

  • 김종춘 (한국화학연구소 안정성연구센터) ;
  • 정문구 (한국화학연구소 안정성연구센터) ;
  • 박종일 (한국화학연구소 안정성연구센터) ;
  • 한상섭 (한국화학연구소 안정성연구센터)
  • Published : 1995.06.01
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Abstract

A teratogenicity study of KTC-1, a new semisynthetic rifamycin antituberculous drug, was conducted in Sprague-Dawley rats. Dosages of KTC-1 0, 7, 21, and 63 mg/kg/day were administered to darns orally gayage from day 7 to day 17 of gestation. Two-third of dams per group were subjected to cesarean section on day 21 of pregnancy for examination of their fetuses, and the remaining one-third of darns per group were allowed to deliver naturally for postnatal examination of their offspring. At 21 mg/kg/day, an increase in the skeletal variations of F1 fetuses and a decrease in the body weight of F1 offspring were seen. At 63 mg/kg/day, a loss in body weight was observed in darns. An increase in fetal death rate, a decrease in litter size and body weight, and an increase in the incidence of visceral malforrnations and skeletal variations were found in F1 fetuses. In particular, lumar rib occurred at an incidence of 31%. In addition, an increase in the dead newborns at birth and neonatal deaths during the lactation period, a loss in body weight, and a decrease in spleen weight were observed in F1 offspring. There were no signs of maternal toxicity or embryotoxicity at 7 mg/kg/day. The results suggest that the no-effect dose level(NOEL)for dams is 21 mg/kg/day, and NOELs for F1 fetuses and offspring are 7 mg/kg/day.

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References

  1. J. of Antibiot. v.34 Antibacterial activity of DL473, a new semisynthetic rifamycin derivative Arioli,V.;Berti,M.;Carniti,G.;Randisi,E.;Rossi,E.;Soctti,R.
  2. The transfer of drugs and other chemicals into breast mil v.72 Committee on drugs, American Academy of Pediatrics
  3. Toxicol. Appl. Pharmacol. v.69 Enhancement of rifampin teratogenicity in cultured rat embryos Greenaway,J.C.;Fantel,A.G.
  4. Early Human Development v.15 Teratology of the antituberculosis drugs Holdiness,M.R.
  5. Cong. Anom. v.16 Differential staining of cartilage and bone in fetal mouse skeletone by alcian blue and alizarin red S Inouye,M.
  6. Teratology v.10 Investigations on the mode of teratogenic action of high doses of rifampicin Jager,E.;Merker,H.J.;Rass,R.
  7. Drug Metab. Rev. v.12 no.1 Metabolism and pharmacokinetics of the antibiotic rifampin Kenny,M.T.;Strates,B.
  8. Chemotherapia v.11 Rifampicin, a new orally active rifamycin Maggi,N.(et al.)
  9. Principles and methods of toxicology Test methods for assessing female reproductive and developmental toxicology Manson,J.M.;Kang,Y.J.;Hayes(ed.)
  10. Cong. Anom. v.27 Spontaneous malformations in laboratory animals: Frequency of external, internal and skeletal malformations in rats, rabbits and mice Morita,H.;Ariyuki,F.;Inomata,N.;Nishimura,K;Kagegawa,Y.;Miyamoto,M.;Watanabe,T.
  11. Cong. Anom. v.14 no.1 A microdissection method for detecting thoracic visceral malformation in mouse and rat fetuses Nishimura,K.
  12. Tuberculosis, Praeger monographs in infectious disease v.2 Schlossberg.D.
  13. Am. Rev. Respir. Dis. v.122 Treatment of tuberculosis during pregnancy Snider,D.E.;Layde,P.M.;Johnson,M.W.;Lyle,M.A.
  14. Lancet v.2 Rifampicin in pregnancy Steen,J.S.M.;Stainton-Ellis,D.M.
  15. Teratology, Principles and Techniques Wilson,J.G.;Warkany,J.
  16. Toxicity test guideline: Collection of notifications related to the pharmaceutical affairs laws(Ⅳ) Yakugyo Jiho Co.
  17. Teratology v.6 Significance of the lumbar rib as an indicator in teratogenicity tests Yasuda,M.;Maneda,H.