The same logic applies to the generation of 4- methylpentanal from VEA, which dominates the distribution of the isomer pair over hexanal. The formation of glyoxal likewise may be enhanced in VEA due to the higher stability of radical intermediates. Diacetyl is thought to be a byproduct of cannabis plants.However, the SIC of C4H6O2 in the vaped THC oil demonstrated multiple isomers of C4H6O2 in that mixture besides diacetyl. From VEA, diacetyl may be generated from the thermal-induced scission of the C−O bond on the acetyl group, which will form acyl radicals that combine to form diacetyl. The formation of a C4H6O2 isomer, 3-oxobutanal, can also be rationalized ; however, there was only one C4H6O2 peak in the vaping aerosol of pure VEA and it has the retention time of diacety lDNPH in our analytical method. Thus, we believe that diacetyl is the main C4H6O2 from VEA, while multiple isomers are likely formed when VEA and THC are vaped together. In some cases, the THC/VEA mixture produced more carbonyl emissions per mg particle mass than the pure compounds . Although this trend is less clear within error, it may suggest some synergetic effects between THC and VEA. Moreover, the THC oil tended to produce a higher amount of acetaldehyde than VEA. VEA degradation may form acetaldehyde , but the unbranched side chain of certain cannabinoids, such as THC and CBG , provides more direct pathways for acetaldehyde formation. Scheme 2 shows that multiple cannabinoids identified in Table 2 may be formed as a result of reactive oxygen addition . While analysis of the THC oil extract did not detect OH-functionalized cannabinoids in the original e-liquid ,flood and drain tray we cannot rule out the possibility that functionalized cannabinoids exist in the unvaped THC oil.
Borille et al.found 123 cannabinoid compounds or metabolites and eight noncannabinoid constituents in the extracts of cannabis plants by ESI-MS, with carbon number ranging from C15 to C55. All molecular formulas of the THC oxidation products in Scheme 2b were also identified in cannabis extracts,suggesting that oxidation from plant metabolism or during extraction could have occurred in addition to vaping. C19H28O3 is identified here as cannabiglendol-C3; C23H34O4 may have multiple isomers ;and C15H16O3/C15H18O3 is identified as cannabispirenone/ cannabispiran.Some compounds in Table 2 still remain unidentified . Due to the uncertainty of the collection efficiency of cannabinoids through the silica cartridge, the quantification reported here for a number of cannabinoids should be considered a lower limit . Cannabinoid emissions per puff increase with temperature at the same e-liquid composition and decrease with VEA addition at the same temperature. Often, chemical emission trends follow the trends in particle mass emission , but yield ratios will indicate if significant chemical transformations occurred during vaping. While the mass yields per mg of particle mass of CBG, Δ9 -THC, CBC, cannabiglendol, OH-cannabinol, and cannflavin B increase with respect to temperature in the vaped THC oil aerosol, it decreases for all of the acids , cannbispirone-A, 10-ethoxy-9-hydroxy THC, and CBN. Compounds such as OH-cannabinol may increase with temperature because they are more efficiently vaporized or are formed through radical-initiated chemistry , adding oxygen functional groups to the carbon skeleton of CBG and THC . The decreasing yield ratio of acids such as THCA is expected with temperature, as they may be degraded through decarboxylation more effectively at higher coil temperatures, a process that also occurs during the initial processing of THC oil, resulting in the formation of neutral cannabinoids .Thus, the large reservoir of THCA present prior to vaping converts to THC while vaping in this third-generation mod device.
The same process occurs from CGBA to CBG, which explains the increasing trend of CBG and THC with temperature. Thermal decarboxylation should be efficient with temperatures above 350 °F ,playing a role to increase the observed yield of neutral cannabinoids. The underlying reasons for the decreasing trend of CBN with temperature is not clear, as CBN is thought to be relatively thermally stable and may be produced from other cannabinoids.Interestingly, when VEA is added, the yields of cannabinoids per mg of particle mass increase at the same temperature for most, but not all, observed compounds. Furthermore, the addition of VEA reverses the temperature trends for some cannabinoids such as THC and CBG, causing their net degradation with temperature. It appears, therefore, that the addition of VEA accelerated both the aerosolization and degradation of many cannabinoids. The reasons for these trends are not apparent, and we cannot rule out that the measurement of particle mass between the two systems introduces sufficient undocumented error to explain these trends. It is possible the cotton wick used for this study exhibited less efficient wicking for the more viscous VEA,which may have caused higher localized temperatures for certain portions of the coil surface despite controlling the temperature in the center of the coil. The temperature, physical integrity of the coil, and the saturation of the wick were monitored to ensure excessive heating did not occur; however, the wicking material remains a limitation of this work as ceramic wicks are more generally used for viscous liquids. For cannabiglendol, OH-cannabinol, and Cannflavin B, a decrease in emission yield was observed when VEA was added. Each of these compounds has multiple polar OH groups that could hydrogen-bond with VEA,which could prevent them from escaping the e-liquid, although it is not clear why this intermolecular interaction would be preferable to those that occur with other cannabinoids. These complex trends may warrant further study. Multiple terpenoids were also quantified in the particles .
Notably, only C15 sesquiterpenes were observed, which are of sufficiently low volatility to remain in the particle and which could represent only a small fraction of the terpene diversity and quantity found in the THC oil extract from cannabis.However, it was not possible to perform a quantification of terpenes in the original e-liquid to compare with that found in the particle composition due to issues pertaining to licensure. Many terpenoids, especially the non-functionalized C10 monoterpenes, are considered volatile organic compounds ; they would preferentially be emitted in the gas phase during vaping. Thus, these terpene observations represent a lower limit as the particle filtration and extraction steps may lose terpenes due to volatilization. The hydroxyl groups of cedrol and nerolidol also help reduce vapor pressure; it is not clear from these data if functionalized terpenes were generated through oxidation or were originally present in the e-liquid. While temperature increases the emissions of terpenes per puff, temperature decreases the terpene yield per mg particle collected from the vaped THC oil . Unlike cannabinoids,indoor grow shelves the addition of VEA did not significantly change terpene yield per mg particle. An exception is cedrol, where the yield at medium temperature increased with VEA addition for unknown reasons. The terpene yield data are consistent with other reports of terpene degradation. Meehan-Atrash et al.identified degradation products from myrcene, limonene, and linalool, including methacrolein, hydroxyacetone, and methyl vinyl ketone.Tang et al.found 11 thermal degradation products from a mixture of terpenoids, 7 of them are carbonyls including formaldehyde, acetaldehyde, acetone, acrolein, methacrolein, valeraldehyde, and hexanal. The methacrolein formed from vaped THC oil likely originates from terpene degradation, and its enhancement with VEA addition may be due to the aforementioned acceleration of volatilization or chemistry,indoor garden table as well as its source from VEA.VEA and cannabinoids are observed to chemically react in the e-cigarettevessel in a manner that is consistent with the degradation of PG and VG in conventional e-cigarettes, i.e., via the thermally induced degradation and/or ROS-induced degradation schemes described by Jensen et al.,Li et al.,and Diaz et al.,among others. ROS such as OH radicals have been directly measured and inferred by degradation product analyses,in e-cigarette vessels and aerosol particles. However, OH sources in the vaping process are not well understood mechanistically. It had been suggested that OH can be formed from O2 insertions into organic molecules, or from redox cycling of redox-active organics and/or transition metals.Thermal degradation carbonyls and acids appear to be formed by C−C bond cleavage of the aliphatic side chain of VEA, with one carbonyl moiety formed at the site of each cleaved carbon . This cleavage process produces two aldehydes at an unbranched site and aldehyde/ketone pair at a branched site. The degradation reactions may be initiated by bond homolysis, dehydration, or H-abstraction and addition by radicals such as OH, followed by the rapid reaction with O2 to form peroxy radicals .
The peroxy radicals can react with other RO2 to form carbonyls or alkoxy radicals.Alkoxy radicals may further react to form carbonyls , alcohols , and possibly alkenes .The primary thermal degradation products may go through further oxidation steps and form more thermal degradation products .The RO2-based mechanisms have been well studied and shown to be important in various chemical systems, like the atmosphere, biological redox, or fuel combustion.These mechanism are consistent with observations, as the most abundant carbonyls observed in the VEA aerosol can be rationalized to be formed from the most stable radicals in the first H-abstraction step . The benzylic radicals are stabilized by the conjugation effect from benzene ring and positive hyperconjugation from the adjacent C−H bonds.The proposed thermal degradation pathway is also supported by the detection of alkenes by Riordan-Short et al.and Mikheev et al.since these compounds are predicted in the proposed mechanism. Thus, our observations suggest that the C−C single bonds on the side chain of VEA are easily oxidized and cleaved during the vaping process, which will cause the formation of a series of carbonyls that have VEA-specific structure and also alkenes and alcohols. These primary products may go through a furtherthermal degradation process to generate secondary thermal degradation products like acids and dicarbonyls. OH radical can add to the unsaturated CC bonds of Δ9 THC and CBG to produce oxygen-functionalized products in the vaping aerosol of THC oil . In contrast to VEA, the oxidation of CBG by OH proceeds primarily through the addition of the double bonds in the side chain, consistent with the oxidation of other alkenes.The mechanism for the following steps is similar to the H-abstraction route. CBG may be the source of unique carbonyl products due to its second unsaturated side chain ; the stepwise mechanism is shown in Scheme S2 for C8H14O. The oxidation may also occur on the unsaturated rings of cannabinoids, such as THC . However, unlike CBG, the allylic site of THC also enables substantial Habstraction by OH in addition to the OH addition occurring at the endocyclic CC, preferentially forming the tertiary alkyl radical . Multiple SIC peaks are found at the m/z representing oxidized products of cannabinoids, suggesting that different isomers abound. Our identification results are consistent with those of Carbone et al.,who utilized NMR for identification. Carbone et al. indicated that peroxide products may also be formed during the oxidation process, a mechanism not shown in our schemes but would be consistent with RO2 chemistry.Although the third-generation temperature-programmable mod vaping device used in this work likely protects from excessive formation of toxic pyrolytic byproducts from cannabis extracts,74 a myriad of thermal degradation and oxidation products were observed at the tested temperatures from cannabinoids, VEA, and terpenes under typical operating conditions. The addition of VEA had complex effects on aerosolization efficiency and product formation that is supplemental to temperature. It is clear that the addition of VEA increases the formation of formaldehyde, glyoxal, 4- methylpentanal, methacrolein, and diacetyl, among other carbonyls per unit of particle mass. Self-titration of THC dose by users may enhance their inhalation exposure to VEA products when the VEA fraction in the e-liquid approaches 100%, due to increasingly higher production of certain carbonyls but increasingly lower emissions of THC and total particle mass. However, at the 1:1 mixture, the particle’s THC yield is also enhanced compared to THC oil extract, which may negate increases in some carbonyl emissions for self-titration purposes. At the same time, VEA addition to the e-liquid had no effect on the observed yields of terpenoids, but a complex effect on the cannabinoid yield. Rich oxidative decomposition chemistry was observed for each compound class in the e-liquid. THC has a stronger tendency to degrade compared to VEA.