Biological Response after 14-Day Cannabidiol and Propylene Glycol Inhalation in Sprague-Dawley Rats.

Objective: Cannabidiol (CBD), a phytocannabinoid of increasing interest for its purported therapeutic effects, is primarily consumed via ingestion and inhalation. While the toxicology of orally administered CBD has been reported, little is known about the effects of CBD inhalation. Doses selected for the present analysis allowed for evaluation of dose-response at concentrations >100-fold higher than typical human consumption levels. Materials and Methods: CBD (98.89% pure) was formulated in propylene glycol (PG) and aerosolized by nebulization to evaluate biological response after nose-only inhalation. Sprague Dawley rats (n = 35 males, 30 females) were exposed to 1.0 and 1.3 mg/L nominal concentrations of CBD and PG, respectively, for 12-180 min. Resulting average daily presented dose ranges were 8.9-138.5 mg/kg CBD and 11.3-176.0 mg/kg PG. Aerosols of 1.4 µm median diameter were achieved. Biological response indicators included clinical signs, clinical chemistry, hematology, body/organ weights, and pulmonary/systemic histopathology. Results: Inflammatory and necrotic responses were observed in the nose at the highest doses of CBD. Limited findings in the larynx and lung were mainly observed at higher doses. There were no histological findings in extrapulmonary organs. Dosimetry modeling differentiated the no observable adverse effect level between the nasal region and lungs to be 2.8 and 10.6 mg/kg CBD, respectively. Conclusions: Dose-depending findings of histological changes in the respiratory tract are observed at high doses. At lower doses consistent with typical over-the-counter vape products there appears to be substantial safety margin in the present study (93- and 353-fold lower for nose and lung, respectively).