Developmental toxicity of dibutyltin dichloride in cynomolgus monkeys.
Dibutyltin dichloride (DBTCl) has been shown to be teratogenic in rats. The present study was conducted to determine the teratogenic potential of DBTCl given to pregnant monkeys during the entire period of organogenesis. Cynomolgus monkeys were dosed once daily by nasogastric intubation with DBTCl at 0, 2.5 or 3.8 mg/kg on days 20-50 of pregnancy, the whole period of organogenesis. The pregnancy outcome was determined on day 100 of pregnancy. In both DBTCl-treated groups, a significant increase in the incidence of pregnant females with soft stool and/or diarrhea, and with yellowish stool was observed. Maternal body weight gain at 3.8 mg/kg and food consumption at 2.5 and 3.8 mg/kg were decreased during the administration period. The survival rate of fetuses at terminal cesarean sectioning was decreased in the DBTCl-treated groups and significantly decreased at 2.5 mg/kg. There were no changes in the developmental parameters of surviving fetuses, including fetal body weight, crown-rump length, tail length, sex ratio, anogenital distance and placental weight, in the DBTCl-treated groups. No external, internal or skeletal malformations were found in the fetuses in any group. Although internal and skeletal variations were found, no difference in the incidence of fetal variation was noted between the control and DBTCl-treated groups. No effect on skeletal ossification was observed in fetuses in the DBTCl-treated groups. The data demonstrate that DBTCl is embryolethal but not teratogenic in cynomolgus monkeys.
Ema
Makoto
M
Division of Risk Assessment, Biological Safety Research Center, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. ema@nihs.go.jp
Fukunishi
Katsuhiro
K
Matsumoto
Mariko
M
Hirose
Akihiko
A
Kamata
Eiichi
E
Ihara
Toshio
T
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003967:Diarrhea / Q000139:chemically induced / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D005313:Fetal Death / Q000139:chemically induced; D008252:Macaca fascicularis; D009947:Organotin Compounds / Q000633:toxicity*; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*
D004785:Environmental Pollutants; D009947:Organotin Compounds; D013723:Teratogens; C020735:dibutyldichlorotin