Reproductive and developmental toxicity evaluation of cannabidiol.

Area of Science:

• Toxicology
• Reproductive Toxicology
• Developmental Toxicology

Background:

• Determining safe cannabidiol (CBD) intake levels requires understanding its reproductive and developmental toxicity.
• Existing data gaps hinder the establishment of consumer safety guidelines for CBD products.

Purpose of the Study:

• To assess the reproductive and developmental toxicity of hemp-derived CBD isolate in a rat model.
• To identify No Observed Adverse Effect Levels (NOAELs) for CBD exposure.

Main Methods:

• Conducted an OECD Test Guideline 421 study in rats with extended postnatal dosing and hormone analysis.
• Administered oral doses of CBD isolate (0, 30, 100, 300 mg/kg-bw/d) to F0 adult animals.
• Monitored maternal toxicity, reproductive performance, reproductive organs, hormone concentrations, gestation length, litter loss, dystocia, and pup development.

Main Results:

• Severe maternal toxicity (mortality, reduced body weight) observed at the highest CBD dose (300 mg/kg-bw/d).
• No effects on F0 testosterone concentrations or reproductive organs; however, high doses caused liver and thyroid changes.
• Limited developmental effects, including reduced pup weights at 300 mg/kg-bw/d and instances of litter loss/dystocia in the high-dose group.

Conclusions:

• The NOAEL for F0 systemic and female reproductive toxicity was 100 mg/kg-bw/d.
• The NOAEL for F0 male reproductive toxicity was 300 mg/kg-bw/d.
• The NOAEL for F1 neonatal and generation toxicity was 100 mg/kg-bw/d.