Developmental toxicity assessment of the new fluoroquinolone antibacterial DW-116 in rabbits.

Abstract

DW-116 is a newly developed fluoroquinolone antibacterial with a broad spectrum against both Gram-positive and Gram-negative bacteria. We have reported recently that DW-116 is embryotoxic and teratogenic in rats. The present study was conducted to investigate the teratogenicity of DW-116, together with maternal toxicity and developmental toxicity using New Zealand White rabbits. The test chemical was administered by gavage to pregnant rabbits from gestational day (GD) 6 through to GD 18 at dose levels of 0, 5, 19.5 and 76.1 mg kg(-1) day(-1). All does were subjected to caesarean section on day 28 of gestation and their foetuses were examined for external, visceral and skeletal abnormalities. In the 76.1 mg kg(-1) group, a minimal maternal toxicity, as evidenced by decreased body weight gain during treatment period, was observed in pregnant rabbits. Significant embryo-foetal toxicity, including increased number of foetal deaths and delayed foetal ossification, was seen. However, no treatment-related morphological changes were detected in foetal external, visceral and skeletal examinations. There were no adverse effects on either pregnant dams or embryo-foetal development at 19.5 and 5 mg kg(-1). It was concluded that administration of DW-116 during the major organogenetic period in rabbits produced decreased maternal body weight gain, increased number of foetal deaths and foetal developmental delay but no evidence of teratogenicity. The no-observed-adverse-effect levels (NOAELs) of DW-116 are considered to be 19.5 mg kg(-1) day(-1) for does and embryo-foetuses, respectively.

• Authors: J C Kim, S H Kim, D H Shin, C S Bae, K S Oh, J H Kim, H I Yun, J H Lim, M K Chung
• Journal: Journal of applied toxicology : JAT (J Appl Toxicol) 2005 Jan-Feb Vol. 25 Issue 1 Pg. 52-9 ISSN: 0260-437X [Print] England
• PMID: 15669036 (Publication Type: Evaluation Study, Journal Article)
• Copyright: Copyright 2005 John Wiley & Sons, Ltd.

Chemical References

• Anti-Bacterial Agents
• DW-116
• Fluoroquinolones
• Piperazines
• Quinolones

Topics

• Animals
• Anti-Bacterial Agents (chemistry, toxicity)
• Body Weight (drug effects)
• Drug Evaluation, Preclinical
• Embryonic Development (drug effects)
• Female
• Fetal Death (chemically induced)
• Fluoroquinolones (chemistry, toxicity)
• Gestational Age
• Molecular Structure
• No-Observed-Adverse-Effect Level
• Piperazines (chemistry, toxicity)
• Pregnancy
• Quinolones (chemistry, toxicity)
• Rabbits