Repeated dose toxicity studies on catena-(S)-[mu-[N alpha-(3-aminopropionyl) histidinato(2-)-N1,N2,O:N tau]-zinc] in rats.
Thirteen- and 52-week oral toxicity studies of Z-103 (catena-(S)-[mu- [N alpha-(3-aminopropionyl) histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) were carried out in rats. In a 13-week repeated dose toxicity study (37.5, 75, 150, 300, 600 or 1200 mg/kg/d), deterioration of the general condition was observed at 300 mg/kg/d or more, a decrease in body weight gain at 600 mg/kg/d or more. Approximately 40% of the animals were found dead or sacrificed in a moribund state at 1200 mg/kg/d. Furthermore, in the 600 mg/kg group changes in urine volume, blood urea nitrogen and weight of kidneys were observed, suggesting that Z-103 may have had adverse effects on the kidney. No sex difference was noted. From these results the no-effect dose level was estimated to be 150 mg/kg/d under the conditions of this experiment. In a 52-week repeated dose toxicity study (18.75, 37.5, 75 or 150 mg/kg/d), proliferation of small duct and atrophy of acinar cells in the pancreas were observed in both sexes of the 150 mg/kg/d group. No other dose-related changes were observed throughout the administration period. Therefore, the no-effect dose level was estimated to be 75 mg/kg/d under this condition.
Matsuda
K
K
Department of Toxicology and Drug Metabolism, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Mera
Y
Y
Wada
H
H
Aruga
H
H
Saik
Y
Y
Taniguchi
Y
Y
D000818:Animals; D000897:Anti-Ulcer Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002336:Carnosine / Q000031:analogs & derivatives*; D004151:Dipeptides / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D010179:Pancreas / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012727:Sex Characteristics; D013997:Time Factors; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine