Reproductive and developmental toxicity studies on catena-(S)-[mu-[N alpha-(3-aminopropionyl) histidinato(2-)-N1,N2,O:N tau]-zinc].
To evaluate the effects of Z-103 (catena-(S)-[mu-[N alpha-(3-aminopropionyl) histidinato (2-)-N1,N2,O:N tau]-zinc], CAS 107667-60-7) on the reproductive performance of male and female rats, the general toxicity of dams, and the development, physical growth and reproductive performance of the next generation, Z-103 was administered to rats prior to, and in the early stages of pregnancy, during the period of fetal organogenesis, and during the perinatal and lactation periods, and to rabbits during the period of fetal organogenesis at the appropriate doses for each study. At the administration of Z-103 prior to and in the early stages of pregnancy in rats, no dose-related abnormalities were observed in the reproductive performance of either sex. Furthermore, there were no death or evidence of teratogenicity or repressive effect on growth in fetuses. Administration of Z-103 during the period of fetal organogenesis in rats affected the growth of embryos and fetuses at 1200 mg/kg. At 600 mg/kg or less, however, there were no death, teratogenicity or repressive effect on growth in fetuses, and furthermore, no dose-related abnormalities were observed in growth, physical development, behavior and reproductive performance in offspring. Administration of Z-103 during the period of fetal organogenesis in rabbits caused a decrease in the number of live fetuses at 300 mg/kg suggesting that 300 mg/kg of Z-103 may have a lethal effect on fetuses. There were, however, neither teratogenicity nor any repressive effect on the growth of fetuses.(ABSTRACT TRUNCATED AT 250 WORDS)
Matsuda
K
K
Department of Toxicology and Drug Metabolism, Zeria Pharmaceutical Co., Ltd., Saitama, Japan.
Nishi
N
N
Hiramatsu
Y
Y
Shimizu
M
M
Ohta
T
T
Kato
M
M
D000014:Abnormalities, Drug-Induced / Q000503:physiopathology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002336:Carnosine / Q000031:analogs & derivatives*; D004151:Dipeptides / Q000633:toxicity*; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D007774:Lactation / Q000187:drug effects; D008297:Male; D009942:Organometallic Compounds / Q000633:toxicity*; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012098:Reproduction / Q000187:drug effects*; D017967:Zinc Compounds
D000897:Anti-Ulcer Agents; D004151:Dipeptides; D009942:Organometallic Compounds; D017967:Zinc Compounds; C061957:polaprezinc; D002336:Carnosine