Developmental toxicity of dibutyltin dichloride given on three consecutive days during organogenesis in cynomolgus monkeys

Abstract

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.

Keywords::

• Developmental toxicity
• embryolethality
• dibutyltin
• monkey

Acknowledgements

This work was supported by Health and Labour Sciences Research Grants (Research on Risk of Chemical Substances: H17-kagaku-ippann-001 and Research on Regulatory Science of Pharmaceuticals and Medical Devices: H17-iyaku-ippann-026) from the Ministry of Health, Labour and Welfare, Japan.