Client
International producer of electronic nicotine delivery systems (ENDS) and e-liquids.
Background
As part of a Premarket Tobacco Product Application (PMTA) for a pod-based ENDS device, bibra was asked to provide support preparing non-clinical and human health impact assessments.
Project goals
With a consideration of PMTA guidance issued by US FDA, the various constituents of the ENDS (notably the e-liquid ingredients, the component materials of the device and the emissions) were subject to human health hazard and risk assessments in order to determine whether the use of the device could be regarded as “appropriate for the protection of the public health” (APPH).
Approach and outcome
As suggested in the PMTA guidance, the available toxicological literature was reviewed for each of the ingredients of the e-liquid (e.g. nicotine, the carriers and flavourings), and human health hazards were identified. Where there were data-gaps, (Quantitative) Structure-Activity Relationship ((Q)SAR) tools were implemented, notably for the genotoxicity and sensitisation endpoints.
Following these hazard reviews, the ingredients were subject to an inhalation-focused risk assessment. This process typically involved defining a Point of Departure (PoD) for each chemical from the available toxicological data, and comparing these benchmarks with estimated exposure levels (under intense and non-intense puffing conditions) in order to quantify any potential health risks to consumers. In addition, acute health risks were considered in the unlikely event that the e-liquid could be accidentally ingested.
Potential leachables that could migrate from the component materials of the device into the e-liquid were evaluated in a similar manner. [see our case study on E&L TRA for an ENDS device for further details]
The emissions produced by the ENDS device were also analysed and evaluated. PMTA guidance specifies that the levels of certain Harmful and Potentially Harmful Constituents (HPHCs) should be accurately quantified, and consumer health risks should be assessed. Bibra therefore performed searches for relevant health-based reference values, for example US EPA inhalation RfCs, for each of the HPHCs, and used these benchmarks to estimate whether the levels determined in suitable analytical studies could pose any potential health risks to consumers. Moreover, these levels were compared to those typically found in the emissions of other ENDS products as well as in tobacco smoke. In addition, Non-Targeted Analyses (NTAs) were performed in order to identify any other chemicals present in the emissions. Using the Threshold of Toxicological Concern (TTC) as well as (Q)SAR analysis as screening tools, potential health risks to these chemical compounds were also considered.
