Posters

      Evaluation of Chronic Inhalation Toxicity of E-Vapor Aerosols in an 18-Month Study in AJ Mice

      Wong, E.; Luettich, K.; Woon, K.; Yeo, Y.; Kratzer, G. F.; Kondylis, A.; Kumar, A.; Smith, C.; Peitsch, M. C.; Hoeng, J.; Lee, K.; Vanscheeuwijck, P.

      Conference date
      Mar 30, 2021
      Conference name
      Society of Toxicology (SOT) Annual Meeting and ToxExpo 2022
      Topic
      Summary

      Many flavor ingredients in e-liquid formulations are ‘generally recognized as safe’ for oral consumption, however there is limited information on their inhalation toxicity especially after repeated exposures. Based on structural grouping, we selected 38 flavor group representatives from a total of 245 flavor chemicals, which were combined as prototype e-liquid formulations and tested in an 18-month inhalation study in AJ mice. The objectives were to characterize and compare the potential impact of flavor containing e-vapor aerosols to the chronic inhalation toxicity of cigarette smoke. Mice were whole-body exposed to air, aerosol from carriers propylene glycol (PG) and vegetable glycerol (VG), PG/VG with nicotine (N, 2% [w/w]), PG/VG/N with flavors (F) at low, medium and high concentrations (4.6 to 18.6% [w/w]), PG/VG/F-High or to mainstream smoke (MS) from the 3R4F reference cigarette for 6 h/day, 5 days/week for up to 18 months. The target aerosol nicotine concentration was set to 15 μg/L. The main endpoints consisted of systemic toxicity (body weight, survival), pulmonary inflammation (bronchioalveolar lavage fluid [BALF] analyses), clinical chemistry, and whole blood analyses. No signs of severe toxicity were noted following exposure to e-vapor aerosols and MS. There were no exposure-related differences in survival rates amongst the female groups, but the survival rate was lower in the male PG/VG/F-High group. Body weights at month 18 were lower in the male PG/VG/F-High and male and female PG/VG/N/F-High groups, however, all the e-vapor aerosol groups showed consistently higher body weights compared to the MS group. In contrast to MS exposure, exposure to the e-vapor aerosols did not cause notable changes in the BALF parameter indicative of lung inflammation. Typical MS-induced changes in serum liver function and erythrocyte parameters were not observed in the e-vapor aerosol groups. While reduced blood lymphocyte counts were observed in the male PG/VG/F-High and PG/VG/N groups, the effect was comparable or significantly lower than those in the MS group. In summary, chronic exposure to flavor e-vapor aerosols under the tested condition did not result in notable chronic toxicity or lung inflammation.

      Related Publications

      Cigarette smoke enhances abdominal aortic aneurysm formation in angiotensin II-treated apolipoprotein E-deficient mice

      Pre-clinical Toxicology

      Tobacco Heating System 2.4 has less harmful impact on 2D bone co-culture system than cigarette smoke

      Pre-clinical Toxicology

      Characterizing the Genotoxic Potential of E-Cigarette Components In Vitro

      Pre-clinical Toxicology

      Evaluation of Chronic Toxicity and Carcinogenicity of Flavored E-Vapor Aerosols in an 18-Month Inhalation Study in A/J Mice

      Pre-clinical Toxicology

      Toxicological Assessment of Highly Mentholated Reduced-Risk Tobacco Products in Sprague Dawley Rats Following Sub-Chronic Inhalation Exposure

      Pre-clinical Toxicology

      Exposure to a Heated Tobacco Product Aerosol Is Associated with Lower Activity of Hepatic Cytochrome P450 Enzymes and Reduced Alteration in Clozapine Metabolism Than Exposure to Cigarette Smoke

      Pre-clinical Toxicology

      PMIScience.com is operated by Philip Morris International for the purpose of publishing and disseminating scientific information about Philip Morris International’s efforts in support of its smoke-free product portfolio. This site is a global site for use by scientists, the public health and regulatory communities, and other stakeholders with an interest in tobacco policy. The purpose of this site is not advertising or marketing, nor is it directed at any specific market. It is not intended for use by consumers. New tobacco products sold in the United States are subject to FDA regulation; therefore the content of this site is not intended to make, and nor should it be construed as making, any product related claims in the United States without proper FDA authorization. ​
      ​
      Reduced Risk Products ("RRPs”) is the term we use to refer to products that present, are likely to present, or have the potential to present less risk of harm to smokers who switch to these products versus continuing smoking. PMI has a range of RRPs in various stages of development, scientific assessment and commercialization. All of our RRPs are smoke-free products that deliver nicotine with far lower quantities of harmful and potentially harmful constituents than found in cigarette smoke.