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Related Experiment Videos

Codeine: developmental toxicity in hamsters and mice.

J Williams1, C J Price, R B Sleet

  • 1Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.

Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology
|April 1, 1991
PubMed
Summary
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Codeine exposure during pregnancy in hamsters and mice caused developmental toxicity, including reduced fetal weight, at doses lower than those affecting maternal health. The hamster was more sensitive, showing effects at a dose 11 times the maximum human therapeutic dose.

Area of Science:

  • Toxicology
  • Developmental Biology
  • Pharmacology

Background:

  • Codeine is a widely used analgesic and antitussive medication.
  • Understanding its potential effects on developing fetuses is crucial for maternal and child health.
  • Previous studies on codeine's developmental toxicity have yielded varied results.

Purpose of the Study:

  • To evaluate the developmental toxicity of codeine in pregnant Syrian hamsters and CD-1 mice.
  • To determine the no-observed-adverse-effect levels (NOAELs) for both maternal and developmental toxicity.
  • To compare the sensitivity of hamsters and mice to codeine's developmental effects.

Main Methods:

  • Timed-pregnant hamsters and mice were administered oral doses of codeine twice daily during critical gestation periods.

Related Experiment Videos

  • Maternal animals were monitored for toxicity, and fetuses were examined for external, visceral, and skeletal malformations.
  • Dose levels ranged from 0 to 150 mg/kg/day in hamsters and 0 to 300 mg/kg/day in mice.

    • Main Results:

    • Maternal toxicity, including weight loss and increased liver weight, was observed at higher doses in both species.
    • Developmental toxicity, evidenced by decreased fetal body weight, occurred at lower doses than maternal toxicity.
    • The NOAEL for developmental toxicity was 10 mg/kg/day in hamsters and 75 mg/kg/day in mice.
    • A specific malformation, meningoencephalocele, was noted in a small percentage of hamster fetuses but was not statistically significant.

    Conclusions:

    • Codeine exhibits developmental toxicity in rodents at doses below those causing maternal toxicity.
    • Hamsters are more sensitive to codeine's developmental effects than mice.
    • The findings suggest a potential risk of developmental toxicity with codeine use during pregnancy, particularly at higher doses.