Aspirin: teratogenic evaluation in the dog.

Area of Science:

• Toxicology
• Developmental Biology
• Pharmacology

Background:

• Aspirin is a widely used medication.
• Understanding its potential developmental toxicity is crucial for risk assessment.
• The dog is often used as a model for human pregnancy studies.

Purpose of the Study:

• To evaluate the teratogenic and embryotoxic potential of aspirin in beagle bitches.
• To determine the effects of aspirin administration timing and dosage on pregnancy outcomes.

Main Methods:

• Beagle bitches were administered aspirin at 100 or 400 mg/kg/day during specific gestational periods (Days 15-22 or 23-30 postmating).
• Control groups received vehicle administration.
• Fetuses were examined for malformations and developmental abnormalities.

Main Results:

• Maternotoxicity was observed in dams receiving 400 mg/kg/day of aspirin.
• A 50% malformation rate was observed in fetuses when dams were treated with 400 mg/kg/day on Days 23-30 postmating.
• Malformations included cleft palate, micrognathia, cardiovascular defects, and tail anomalies.
• No teratogenic effects were noted at 100 mg/kg/day or when 400 mg/kg/day was given on Days 15-22.
• Spontaneous malformation rates in control groups were very low.

Conclusions:

• Aspirin, particularly at higher doses and later gestational stages, poses a teratogenic risk in beagle bitches.
• The timing of aspirin administration significantly influences its developmental toxicity.
• The study supports the utility of the dog as a suitable animal model for teratogenic screening of drugs.