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

• Published in: Journal of applied toxicology Vol. 25; no. 1; pp. 52 - 59
• Main Authors: Kim, J. C., Kim, S. H., Shin, D. H., Bae, C. S., Oh, K. S., Kim, J. H., Yun, H. I., Lim, J. H., Chung, M. K.
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.01.2005; Wiley
• Subjects: Animals; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - toxicity; antimicrobial agents; Biological and medical sciences; Body Weight - drug effects; Drug Evaluation, Preclinical; Drug toxicity and drugs side effects treatment; DW-116; Embryonic Development - drug effects; embryotoxicity; Female; Fetal Death - chemically induced; Fluoroquinolones - chemistry; Fluoroquinolones - toxicity; Gestational Age; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Molecular Structure; No-Observed-Adverse-Effect Level; Pharmacology. Drug treatments; Piperazines - chemistry; Piperazines - toxicity; Pregnancy; quinolones; Quinolones - chemistry; Quinolones - toxicity; Rabbits; teratogenicity; Embryo; Toxicity; rabbits; Rabbit; Lagomorpha; Antimicrobial agent; Teratogenesis; Vertebrata; Fluoroquinolone derivatives; Mammalia; DW-116; antimicrobial agents; Animal; embryotoxicity; quinolones; Teratogen; Antibacterial agent; teratogenicity
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.1033

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. Copyright © 2005 John Wiley & Sons, Ltd.