Developmental toxicity of dibutyltin dichloride given on three consecutive days during organogenesis in cynomolgus monkeys.
We previously reported that the administration of dibutyltin dichloride (DBTCl) by nasogastric intubation during the entire period of organogenesis, days 20-50 of pregnancy, was embryolethal, but not teratogenic, in cynomolgus monkeys. The present study was conducted to further evaluate the developmental toxicity of DBTCl given to pregnant monkeys on 3 consecutive days during organogenesis. Cynomolgus monkeys were given DBTCl at 7.5 mg/kg body weight/day by nasogastric intubation on days 19-21, 21-23, 24-26, 26-28, 29-31, 31-33, or 34-36 of pregnancy, and the pregnancy outcome was determined on day 100 of pregnancy. Embryonic/fetal loss was observed in 1 female given DBTCl on days 19-21, 2 females given DBTCl on days 24-26, and 1 female given DBTCl on days 34-36. There were no effects of DBTCl on developmental parameters in surviving fetuses, including fetal body weight, crown-rump length, tail length, or placental weight. No external, internal, or skeletal malformations were detected in fetuses in any group. DBTCl did not affect the incidence of fetuses with skeletal variation or skeletal ossification of fetuses. These data confirm our previous findings that DBTCl was embryolethal, but not teratogenic, in cynomolgus monkeys.
Ema
Makoto
M
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan. ema@nihs.go.jp
Arima
Akihiro
A
Fukunishi
Katsuhiro
K
Matsumoto
Mariko
M
Hirata-Koizumi
Mutsuko
M
Hirose
Akihiko
A
Ihara
Toshio
T
D000014:Abnormalities, Drug-Induced / Q000209:etiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018568:Crown-Rump Length; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects / Q000502:physiology; D047108:Embryonic Development / Q000187:drug effects* / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D008252:Macaca fascicularis; D009929:Organ Size; D038081:Organogenesis / Q000187:drug effects* / Q000502:physiology; D009947:Organotin Compounds / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects
D009947:Organotin Compounds; C020735:dibutyldichlorotin