Phytol, not propylene glycol, causes severe pulmonary injury after inhalation dosing in Sprague-Dawley rats. 2021

Daniela Schwotzer, and Andrew Gigliotti, and Hammad Irshad, and Wendy Dye, and Jacob McDonald
Lovelace Biomedical, Albuquerque, NM, USA.

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.

UI MeSH Term Description Entries
D008297 Male Males
D010836 Phytol Acyclic diterpene used in making synthetic forms of vitamin E and vitamin K1.
D005260 Female Females
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D055370 Lung Injury Damage to any compartment of the lung caused by physical, chemical, or biological agents which characteristically elicit inflammatory reaction. These inflammatory reactions can either be acute and dominated by NEUTROPHILS, or chronic and dominated by LYMPHOCYTES and MACROPHAGES. E-Cigarette Use-Associated Lung Injury,E-Cigarette or Vaping Product Use-Associated Lung Injury,EVALI,Vaping Product Use-Associated Lung Injury,Chronic Lung Injury,Lung Injuries,Pulmonary Injury,Chronic Lung Injuries,E Cigarette Use Associated Lung Injury,E Cigarette or Vaping Product Use Associated Lung Injury,EVALIs,Injuries, Lung,Injuries, Pulmonary,Injury, Lung,Injury, Pulmonary,Lung Injuries, Chronic,Lung Injury, Chronic,Pulmonary Injuries,Vaping Product Use Associated Lung Injury
D019570 Inhalation Exposure The exposure to potentially harmful chemical, physical, or biological agents by inhaling them. Exposure, Inhalation,Exposures, Inhalation,Inhalation Exposures
D019946 Propylene Glycol A clear, colorless, viscous organic solvent and diluent used in pharmaceutical preparations. 1,2-Propanediol,Propan-1,2-Diol,Propylene Glycol Monohydrate,Propylene Glycol Sodium Salt,Propylene Glycol, (+-)-Isomer,Propylene Glycol, (R)-Isomer,Propylene Glycol, (S)-Isomer,1,2 Propanediol,Glycol, Propylene,Monohydrate, Propylene Glycol

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