An isomer of 2,3,5-trimethyl-1,4-benzenediol has also recently been identified as a substantial VEA degradation product at temperatures 220˚C. Authentic standards were purchased for 2-methyl-1-heptene, phytol, and 2,3,5-trimethyl-1,4-benzenediol to confirm identities of observed products . Other compounds, such as vitamin E, DQ, DHQ, 1-pristene, and 3,7,11-trimethyl-1-dodecanol, have been consistently identified as VEA decomposition products. Several products, such as DHQMA or ketene, that have been previously reported in VEA vaping emissions could not be found in our spectra, likely due to the limitations of the emission collection and analysis method described in section 3.4. A heat map of the mass fractions of degradation products generated at each temperature is shown in Fig 4. Products that contribute to the majority of the observed VEA degradation were separated from the total heat map to better visualize the change in each concentration as a function of temperature. VEA, 1-pristene, and 3,7,11-trimethyl- 1-dodecanol were found to be the most dominant vaping emission products at all of temperature settings, while other compounds, such as duroquinone, durohydroquinone, and 2-methyl-1-heptene steadily increase in concentration as temperature increases. Furthermore, certain compounds including 2,3,5-trimethyl-1,4-benzenediol, 2,6-dimethyl-1,6-heptadiene, 3,7-dimethyl-1-octene, and 3-methyl-1-octene are not produced in concentrations above the detection limit of our instrument until 322˚C,cannabis grow system which suggests a potential risk that users who operated vaping devices at lower temperatures would not be exposed to. However, while most identified compounds appear to increase in concentration as temperature increases, phytol and 2,6,10-trimethyl-dodecane are produced at detectable levels at 176 and 237˚C but cannot be found at higher temperatures.

Another recent study has also detected production of phytol when vitamin E were heated in a micro-chamber/thermal extractor at 250˚C. It is possible that at these compounds are stable at lower temperatures but begin to break down into degradation products themselves as the temperature increases. Another important pattern to note is the increase in compounds that may pose a risk of oxidative damage to lungs, such as DQ and 2,3,5-trimethyl-1,4-benzenediol, at higher concentrations. While not investigated in this study, prior research has shown that increased temperature may result in the enhanced emission of carbonyl-containing compounds when vaping e-liquids containing propylene glycol and glycerin. Thus, vaping VEA at greater temperature settings may also carry the risk of exposure to highly electrophilic molecules and subsequent oxidative lung injury. In order to better understand the interactions between temperature and the generated emission products, a Pearson correlation analysis was performed . Overall, all but fourof the identified compounds were strongly correlated with temperature . Compounds such as DQ, 1-pristene, 2-methyl-1-heptene, 2-hydroxy-4-methoxy-3,6-dimethyl benzaldehyde, and 2,6-dimethyl-1,6-heptadiene, were very well correlated with temperature , indicating a strong increase in concentration as temperature increases. VEA and phytol, in contrast, were strongly anti-correlated with temperature , while VE and 2,6,10-trimethyl-dodecane were moderately anti-correlated with temperature . In addition, VEA was found to be weakly to strongly anti-correlated with all degradation products excepting phytol and VE, which demonstrate a strong positive correlation . These results support our analysis of the mass fractions, indicating that as temperature increases, thermal decomposition of VEA is heightened. Further analysis of the correlations between degradation products shows that phytol is strongly anti-correlated with all VEA degradation products with the exception of 2,6,10-trimethyl-dodecane, which was found to have a strong positive correlation with phytol .

Phytol was also found to be strongly correlated with VEA , likely because as more VEA was evaporated during the vaping process, the greater the chance of degradation into phytol. These relationships further suggest that while some degradation products may be stable at high temperatures, phytol may further decompose into shorter-chain alcohols, alkanes, and alkenes and enhance the production of VEA vaping emission products. Phytol is known both as a precursor for the synthesis of VE and vitamin K12, as well as a byproduct of chlorophyll degradation. Inhalation of aerosolized phytol has previously been shown to induce lung injury in exposed rats. In addition, phytol is a long chain alkyl alcohol compound, meaning that it has the potential to induce damage to the membrane of cells in a biological system. Overall, the toxicity of phytol raises questions about the safety of vaping not only VEA but cannabis-containing vape products that may result in phytol production. These results clearly indicate that the product distributions of VEA vaping emissions are highly dependent on the operating temperature of the vape pen. As a result, the exposure for vape users operating the same e-cigarette products at different temperatures may differ significantly.Previous reports of VEA pyrolysis indicate that VEA begins to degrade starting at ~200–240˚C. However, our results clearly demonstrate degradation of VEA and formation of products such as DQ at 176˚C, indicating that the device itself may play a larger role in the decomposition of VEA than initially anticipated. Previous study in our lab has also found substantial formation of DQ at 218˚C–several hundred degrees lower than what has been predicted. To further understand if the device itself may impact the thermal degradation of VEA, pure pyrolysis of VEA oil was carried out using a tube furnace reactor.At 176 and 237˚C, VEA was fairly stable; substantial consumption of VEA oil was not observed until the two higher temperatures, despite clear consumption at all temperatures during the vaping collection.

Fig 6 demonstrates the product distribution of VEA degradation products collected and analyzed using GC/MS. Here, we did not observe substantial thermal decomposition of VEA when heated at 176˚C for 75 minutes, which greatly contrasts with the degradation of VEA at 176˚C for only 4 s during the vaping collection. At 237˚C, the parent VEA molecule was the only detectable emission product, indicating that VEA again did not degrade at this lower temperature, though 237˚C was enough to evaporate VEA so that it could be collected in the cold trap. Degradation products were only detectable from samples collected at 322 and 356˚C, though the number of products and abundance of observed peaks are drastically reduced when compared to the vaping emissions. It should be noted that the tube furnace is capable of heating VEA at more accurate and consistent temperatures than the vape pen itself, which often saw temperature fluctuations that may influence results. The stark difference in product distribution provides evidence that VEA vaping emissions may not be the result of pure pyrolysis alone. Instead, external factors such as the device elements themselves or environmental interactions may play a role in the catalysis of VEA degradation. The cartridge used in this study is a newer THC cartridge that contains a ceramic heating element, a nichrome filament wire, a fibrous wick/insulation wrap through which oil was delivered to the heating element, and a stainless steel air flow tube and heating element housing that the oil remained in direct contact with. The emission of metals during the vaping process has been documented in several prior studies, but the interaction between VEA and the metal components of the vape device are still being investigated. Saliba et al. recently found that interaction between a metal heating element and PG greatly decreased the temperature required to observe PG thermal decomposition. Certain metals such as stainless steel, which is present in the cartridge used in this study,cannabis grow lights resulted in a nearly 300˚C reduction in required temperature compared to pure pyrolysis, highlighting a clear interaction between the PG decomposition and the device itself. Furthermore, a study by Jaegers et al. found that pyrolysis alone in an anaerobic environment was not able to induce thermal degradation of PG and VG at low temperatures , despite previous studies observing degradation at temperatures as low as 149˚C during vaping. However, when heated in an aerobic environment, thermal decomposition was observed at 133 and 175˚C, both without and with the addition of metal oxides Cr2O3 and ZrO2, suggesting that oxidation is a key process during vaping. In combination with the results shown here, evidence highly suggests that pure pyrolysis alone may not be the only pathway for VEA degradation. During the vaping process, not only may VEA come into direct contact with metals that are present in the filament wire or stainless-steel body, but VEA must also come into contact with molecular oxygen in ambient air. These interactions may promote VEA degradation at temperatures lower than predicted under pure pyrolysis conditions. Ultimately, it is then possible that compounds such as DQ or ketene may be able to form at lower temperatures than what is theoretically calculated if these interactions are considered.However, further study is required to fully understand the effects of the e-cigarette device and vaping environment on the degradation of e-liquids.First, this study presents a range of decomposition products that were identified using a -40˚C cold trap and GC/MS analysis.

Approximately 40% of the mass of VEA consumed by the vape pen could be attributed to the compounds identified here. However, compounds with high vapor pressure, such as ketene, that have been previously reported from VEA pyrolysis may not have been efficiently captured using the cold trap method described in this study. This method is expected to better traps particle-phase compounds that are able to condense at -40˚C and are stable enough to transfer from the cold trap to collection vials at room temperature and is unable to capture highly volatile or reactive VEA vaping emission products. For example, ketene, which is expected to form during VEA pyrolysis, has an estimated boiling point of -56˚C and, as a result, was not expected to be observed in our collection. Furthermore, highly volatile and/or reactive compounds such as ketene and various low molecular weight carbonyl-containing species, etc., often require additional derivatization methods that were not used in this study to be observed using GC/MS. This study was also only able to identify compounds with mass spectra that could be found in the NIST mass spectral library. While PubChem currently reports over 111 million unique chemical structures, the NIST library used in this study contains MS fragmentation patterns for only 242,466 compounds. As such, a large portion of the TIC for each collection could not be matched to a known compound . Furthermore, several peaks were observed that were believed to be co-elution of two or more products, which prevented clear analysis of the fragmentation patterns. Several identified products, such as VEA, may also have multiple isomeric forms that have only slight differences in their retention times and mass spectra that the NIST library matching program is unable to account for. In the case of VEA, all peaks were assumed to be and quantified as the same α form, but it is possible for VEA to exist in α, β, γ, or δ forms. This may be true for other structures identified in this study. The use of QCEIMS to identify products that cannot be found in the NIST database, such as 1-pristene, is a potential avenue for further identification of vaping product emissions, though its use for non-target analysis is limited if the researcher does not have a proposed structure in mind to simulate fragmentation. While this study was able to account for ~40% of the mass consumed by the pen during the vaping process, the remaining mass is likely attributable to these uncaptured volatile or reactive products, as well as degradation products that were captured, but unable to be identified at this time. Finally, the vaping topography used in this study was adapted from previous literature on nicotine vaping and optimized for capture of particles in the cold trap system. Real-word nicotine vape users have been reported to inhale between 50–80 mL/puff at greater flow rates than used in this study, whereas parameters for THC-vaping have not been well-characterized at this time. The production yields of VEA degradation products reported in this study could consequently differ for those who vaped at higher flow rates. The temperature dependence of product distribution, however, remains true.This is the first large scale randomized trial that provides the opportunity to compare the treatment retention of participants on buprenorphine and methadone in community treatment programs in the U.S. The results demonstrate that those treated with BUP were more than 50% less likely to remain in treatment for 24 weeks than those receiving MET. This finding is consistent with other controlled trials or observational studies, even including studies that focused on special populations such as pregnant patients.19