Phytol, not propylene glycol, causes severe pulmonary injury after inhalation dosing in Sprague-Dawley rats

Abstract

Introduction: The use of vaping pens for inhalation of cannabinoid derived products is rising and has become a popular alternative to smoking combustible products. For efficient product delivery, additives are sometimes added and vaping pens often may include compounds like Phytol or Propylene Glycol as thinning agents. This study aimed at comparing Phytol and Propylene Glycol with respect to potential toxicity and safe use in vaping products.

Methods: Male and female Sprague Dawley rats were exposed to 5 mg/L of Phytol or Propylene Glycol for up to 6 hours over up to 14 days and monitored for clinical signs and changes in body weight. Gross necropsy and histopathology of respiratory tissue was performed to assess potential adverse effects.

Results: Phytol exposed animals expressed severe clinical signs, body weight loss and mortality after one or two exposure days, leading to termination of all dose groups for this compound. Lung weights were increased and respiratory tissue was severely affected, demonstrating dose-responsive tissue degeneration, necrosis, edema, hemorrhage and inflammation. Propylene Glycol exposed animals did not show any adverse reactions after 14 days of high dose exposure.

Conclusions: For Phytol, a low observed adverse effect level (LOAEL) was determined at ≤109.0/10.9 mg/kg/day presented/deposited dose and therefore its use as excipient in vaping product is not recommend; a safe exposure range was not established for Phytol. Propylene Glycol, in contrast, is considered safe with a no observed adverse effect level (NOAEL) at 1151.7/115.2 mg/kg/day presented/deposited dose in rats.

Keywords:

• Vaping
• cannabidiol
• phytol
• propylene glycol
• nose-only inhalation

Disclosure statement

The study was commissioned by Canopy Growth USA, LLC (CG) with the intent of comparing two potential excipients for their potential product portfolio. Experiments were designed, performed, and interpreted independently by Lovelace Biomedical scientists without influence from CG.