The US Food and Drug Administration (FDA) recently published a “Proposed Rule” for the Electronic Nicotine Delivery Systems (ENDS) sector. This guide outlines how the new Proposed Rule relates to the...
Nicotine
A study recently published by the Journal of the American College of Cardiology reports that acute exposure of endothelial cells to flavored e-cigarette liquids, most notably cinnamon-flavored, led to an increase in cellular effects considered to precede cardiovascular disease. Unsurprisingly, media outlets have already picked up on this story and asserted that vaping flavored e-liquids could increase the risk of heart attack. Although the results add to a number of published studies reporting that cinnamon-flavored e-liquids can increase potentially adverse cellular effects, a balanced examination must be performed before concluding that vaping flavored e-liquids increase the risk of cardiovascular disease.
What the study does show:
✔ Unvaped e-liquid added directly to cells significantly decreased cell viability and increased reactive oxygen species and inflammatory markers compared to unexposed cells.
What the study doesn’t show:
× Aerosol generated (vaped) from cinnamon-flavored e-liquids increases adverse cellular effects.
Studies performed with e-cigarette aerosol are more relevant exposure scenarios to assess potential health risks for e-cigarette consumers.
× Liquid dosing levels to cells used in the study can be extrapolated to real consumer use.
Studies identifying potential hazards from liquid only exposures have limited utility in quantifying and predicting human health risk from e-cigarette exposures.
× E-liquids increase cardiovascular risks compared with combustible cigarettes.
Establishing comparative effects to combustible cigarettes is essential for addressing harm reduction for the majority of the e-cigarette consumer population.
× This cell assay is a validated model for cardiovascular disease in humans.
Conclusions on human health effects should not be made solely from unvalidated, cell-based studies.
× Individual flavor chemical(s) are responsible for the cellular effects.
Studies should identify chemical formulations and quantities and include unflavored controls to assess the potential health risk of e-liquid chemical exposures.
Implications for US companies considering a PMTA
Cardiovascular disease is a potential health outcome from tobacco use. PMTA submissions should address potential cardiovascular effects by acknowledging and critically evaluating the body of evidence (in vitro, in vivo, clinical studies). As FDA indicated in the IQOS PMTA TPL, unvalidated assays have unknown utility for regulatory use and do not contribute significantly to a weight of evidence analysis. In the absence of a validated, in vitro, regulatory assay for cardiovascular effects, manufactures can examine the toxicology of e-liquid ingredients using desk based toxicology methods, assessing published studies, and examining acute endpoints (heart rate, systolic blood pressure, diastolic blood pressure) in clinical studies.
Use a systematic approach to evaluate flavors
A robust scientific approach involves considering the overall weight of evidence before determining if the cardiovascular effects of vaping a flavored liquid are similar to that of combustible cigarette smoking. To understand how the flavors in your product may impact on a PMTA application, or for a review of the safety of the flavors in your products, contact us today.
