Developmental toxicity evaluation of the new fluoroquinolone antibacterial DW-116 in rats.
We have recently reported that the fluoroquinolone antibacterial DW-116 induces a significant developmental toxicity in rat. The present study was conducted to better understand the teratogenic effects of DW-116 at several developmental toxic doses in rats. DW-116 was orally administered to pregnant rats from gestational day (GD) 6 through 16 at dose levels of 0, 320, 400, and 500 mg/kg/day. All dams were subjected to caesarean section on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. At above 400 mg/kg, severe decreases in maternal body weight gain, food consumption, litter size, fetal weight and placental weight, and severe increases in resorption rate and fetal morphological alterations were observed. At 320 mg/kg, mild decreases in maternal body weight gain, food consumption, fetal weight and placental weight, and mild increases in fetal variations and retardations were observed. These results suggest that DW-116 is embryotoxic at above 320 mg/kg/day and is embryolethal and teratogenic at above 400 mg/kg in pregnant rats and that DW-116 is a selective developmental toxicant in rat conceptuses.
Kim
Jong-Choon
JC
College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea. toxkim@chonnam.ac.kr
Shin
Dong-Ho
DH
Kim
Sung-Ho
SH
Ahn
Tae-Ho
TH
Kang
Seong-Soo
SS
Jang
Beom-Su
BS
Kim
Choong-Yong
CY
Chung
Moon-Koo
MK
D000014:Abnormalities, Drug-Induced / Q000235:genetics; D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005314:Embryonic and Fetal Development / Q000187:drug effects* / Q000235:genetics; D005260:Female; D020567:Fetal Weight / Q000187:drug effects / Q000235:genetics; D005333:Fetus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D024841:Fluoroquinolones; D005865:Gestational Age; D008431:Maternal-Fetal Exchange / Q000187:drug effects / Q000235:genetics; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects / Q000235:genetics; D010879:Piperazines / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D010920:Placenta / Q000187:drug effects; D011247:Pregnancy; D015363:Quinolones / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000890:Anti-Infective Agents; C097673:DW-116; D024841:Fluoroquinolones; D010879:Piperazines; D015363:Quinolones