The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
TERATOLOGICAL STUDY OF CEFPIROME SULFATE IN RATS
Osamu SUGIYAMAKoichi TANAKAMayumi TOYAShinichi IGARASHIKazuto WATANABESonoko WATANABEKoichiro TSUJIYasunori KUMAGAI
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Keywords: rat
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1990 Volume 15 Issue SupplementIII Pages 65-89

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Abstract

A teratogenicity study was pertormed in rats by intraperitoneal or intravenous administration of cefpirome sulfate (CPR) at dose level of 0 (control), 200, 400 and 800 mg/kg/day to dams from day 7 to day 17 of pregnancy. Twenty one to twenty eight female rats in each intraperitoneal and intravenous administrated group were sacrificed on day 21 of pregnancy for examination of their fetuses, and ten to thirteen female rats in each intraperitoneal administrated group were allowed to deliver for the postnatal examination of their offsprings. In the 800 mg/kg/day intravenous administrated group, two dams out of twenty four died during administration period, however no animal died in any intraperitoneal administrated group. The doses of 400 and 800 mg/kg/day caused piloerection, diarrhea or loose feces in the both administration routes, and accelerated breathing, a decrease in spontaneous activity, systemic spasms, cataleptic symptoms and wild running in the intravenous route. The suppression of body weight gain was detected in the 800 mg/kg/day intraperitoneal administrated group and 200, 400 and 800 mg/kg/day intravenous administrated groups, however there were no significant differences in food and water intakes between treated and control groups. At autopsy, enlargement of caecum and an increase in adrenal weight were detected in the 800 mg/kg/day groups of both administration routes. Body weight of the fetuses was decreased in both sexes in the 800 mg/kg/day group and in male fetuses in the 400 mg/kg/day group, and placental weight was decreased in the 800 mg/kg/day group, in the both administration routes respectively. However, embryonal or fetal mortality and incidences of external or visceral anomalies were not increased. In offspring, the dose of 800 mg/kg/day caused very slight suppression of body weight gain, however CPR had no adverse effects on the postnatal development such as viability, differentiation, emotionality, learning ability or reproductive performance. The results suggest that the non-effective dose level of CPR is 200 mg/kg/day in maternal animals and fetuses, 400 mg/kg/day in offsprings in intraperitoneal route, lower than 200 mg/kg/day in maternal animals and 200 mg/kg/day in fetuses in intravenous route respectively.

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