Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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A 4-week Repeated Oral Dose Toxicity Study of CJ-10882 in Dogs

  • Cha, Shin-Woo (Korea Institute of Toxicology, Yuseong) ;
  • Kim, Jong-Choon (Department of Pharmacology and Toxicology, College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Dal-Hyun (R＆D Center of Pharmaceuticals, Cheil Jedang Co.) ;
  • Chung, Moon-Koo (Korea Institute of Toxicology, Yuseong) ;
  • Junghee Han (Korea Institute of Toxicology, Yuseong)
  • Published : 2002.09.01
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Abstract

The present study was conducted to investigate the potential subacute toxicity of CJ-10882 by a 4-week repeated oral dose in dogs. The test article was administered once dally by gavage to dogs at dose levels of 0, 2, 10, and 50 mg/kg/day for 4 weeks. During the test period, clinical signs, mortality, body weights, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross finding, organ weight, and histopathology were evaluated. Several clinical sign were observed in treated dogs at 50 mg/kg, including salivation and vomiting. Increase in the serum level of ALT and albumin observed in the female 50 mg/kg group was considered as a toxic effect related to the test article since the histopathological change in Liver was accompanied. There were no treatment-related effects on mortality, food and water consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, necropsy findings and organ weights in any treatment group. Based on these results, target organ was not observed and the no-observed-adverse-effect level (NOAEL) was 10 mg/kg/day and the absolute toxic dose was 50 mg/kg for both male and female dogs.

Keywords

References

  1. Clin. Exp. Allergy v.26 Anti-inflammatory effects of theophylline and selective phosphodiesterase inhibitors Banner,K.H.;Page,C.P.
  2. Biochem. Pharmacol. v.51 Association of the anti-inflammatory activity of phosphodiesterase 4(PDE Ⅳ) inhibitors with either inhibition of PDE Ⅳ catalytic activity or competition for [³H]rolipram binding Barnette,M.S.;Bartus,J.O.;Burman,M.;Christensen,S.B.;Cieslinski,L.B.;Esser,K.M.;Prabhakar,U.S.;Rush,J.A.;Torphy,T.J. https://doi.org/10.1016/0006-2952(96)00053-6
  3. Prog. Nucleic. Acid Res. Mol. Biol. v.63 The molecular biology of cyclic mucleotide phosphodiesterases Conti,M.;Jin,S.L. https://doi.org/10.1016/S0079-6603(08)60718-7
  4. Pharmacol. Toxicol v.78 The toxicity of repeated exposure to rolipram, a type Ⅳ phosphodiesterase inhibitor, in rats Larson,J.L.;Pino,M.V.;Geiger,L.E.;Simeone,C.R. https://doi.org/10.1111/j.1600-0773.1996.tb00178.x
  5. Curr. Opin. Cell Biol. v.12 Regulation of cAMP and cGMP signaling:new phosphodiesterases and new functions Sodering,S.H.;Beavo,J.A. https://doi.org/10.1016/S0955-0674(99)00073-3
  6. Am. J. Respir. Crit. Care Med. v.157 Phosphodiesterase isozymes: molecular targets for novel antiasthma agents Torphy,T.J. https://doi.org/10.1164/ajrccm.157.2.9708012
  7. Taylor and Francis Target organ pathology; A basic text Turton,J.;Hooson,J.
  8. J. Toxicol. Environm. Health v.10 Reference range data base for serum chemistry and hematology values in laboratory animals Wolford,S.T.;Schreer,R.A.;Gohs,F.A.;Gallo,P.P.;Brodeck,M.;Folk,H.B.;Ruhren,R.