Developmental toxicity evaluation of Bendectin in CD rats.

Area of Science:

• Toxicology
• Developmental Biology
• Pharmacology

Background:

• Bendectin (doxylamine succinate and pyridoxine HCl) was a prescribed antinauseant for pregnancy.
• Previous concerns existed regarding its potential teratogenicity.
• This study investigates maternal and developmental toxicity in a rodent model.

Purpose of the Study:

• To evaluate the maternal and developmental effects of Bendectin administration during organogenesis.
• To determine dose-response relationships for toxicity and malformations.
• To establish a safety profile for Bendectin in pregnant rats.

Main Methods:

• Timed-pregnant CD rats received Bendectin (0, 200, 500, 800 mg/kg/day) via oral gavage from gestational days 6-15.
• Maternal parameters (food/water consumption, weight gain, mortality) were monitored.
• Fetuses were examined for external, visceral, and skeletal abnormalities at gestational day 20.

Main Results:

• Maternal toxicity (reduced food intake, weight gain, sedation) observed at 500 and 800 mg/kg/day.
• Maternal mortality (17.1%) occurred only at the highest dose (800 mg/kg/day).
• Developmental effects included reduced prenatal viability and fetal weight at higher doses; skeletal variations (reduced ossification) noted across doses, with increased malformed litters (short 13th rib) only at 800 mg/kg/day.

Conclusions:

• Bendectin induced maternal toxicity and developmental effects, including skeletal variations, at higher doses.
• Increased incidence of malformed litters was observed only at maternally toxic and lethal doses.
• The study suggests a dose-dependent safety margin for Bendectin's developmental toxicity.