Developmental toxicity assessment of the new fluoroquinolone antibacterial DW-116 in rabbits.
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.
Kim
J C
JC
College of Veterinary Medicine, Chonnam National University, Gwangju 500-757, Republic of Korea.
Kim
S H
SH
Shin
D H
DH
Bae
C S
CS
Oh
K S
KS
Kim
J H
JH
Yun
H I
HI
Lim
J H
JH
Chung
M K
MK
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D024841:Fluoroquinolones / Q000737:chemistry / Q000633:toxicity*; D005865:Gestational Age; D015394:Molecular Structure; D019055:No-Observed-Adverse-Effect Level; D010879:Piperazines / Q000737:chemistry / Q000633:toxicity*; D011247:Pregnancy; D015363:Quinolones / Q000737:chemistry / Q000633:toxicity*; D011817:Rabbits
D000900:Anti-Bacterial Agents; C097673:DW-116; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones