A First-Tier Framework for Assessing Toxicological Risk from Vaporized Cannabis Concentrates.

Vaporization is an increasingly prevalent means to consume cannabis, but there is little guidance for manufacturers or regulators to evaluate additive safety. This paper presents a first-tier framework for regulators and cannabis manufacturers without significant toxicological expertise to conduct risk assessments and prioritize additives in cannabis concentrates for acceptance, elimination, or further evaluation. Cannabinoids and contaminants (e.g., solvents, pesticides, etc.) are excluded from this framework because of the complexity involved in their assessment; theirs would not be a first-tier toxicological assessment. Further, several U.S. state regulators have provided guidance for major cannabinoids and contaminants. Toxicological risk assessment of cannabis concentrate additives, like other types of risk assessment, includes hazard assessment, dose-response, exposure assessment, and risk characterization steps. Scarce consumption data has made exposure assessment of cannabis concentrates difficult and variable. Previously unpublished consumption data collected from over 54,000 smart vaporization devices show that 50th and 95th percentile users consume 5 and 57 mg per day on average, respectively. Based on these and published data, we propose assuming 100 mg per day cannabis concentrate consumption for first-tier risk assessment purposes. Herein, we provide regulators, cannabis manufacturers, and consumers a preliminary methodology to evaluate the health risks of cannabis concentrate additives.

A simple predictive model for estimating relative e-cigarette toxic carbonyl levels.

E-cigarette devices are wide ranging, leading to significant differences in levels of toxic carbonyls in their respective aerosols. Power can be a useful method in predicting relative toxin concentrations within the same device, but does not correlate well to inter-device levels. Herein, we have developed a simple mathematical model utilizing parameters of an e-cigarette's coil and wick in order to predict relative levels of e-liquid solvent degradation. Model 1, which is coil length/(wick surface area*wraps), performed in the moderate-to-substantial range as a predictive tool (R2 = 0.69). Twelve devices, spanning a range of coil and wick styles, were analyzed. Model 1 was evaluated against twelve alternative models and displayed the best predictability. Relationships that included power settings displayed weak predictability, validating that power levels cannot be reliably compared between devices due to differing wicking and coil components and heat transfer efficiencies.

Triacetin Enhances Levels of Acrolein, Formaldehyde Hemiacetals, and Acetaldehyde in Electronic Cigarette Aerosols.

The health effects of inhaled electronic cigarette (e-cigarette) flavoring compounds are largely unknown. Earlier reports of their chemical reactivity have been conflicting, with some claiming, for example, that the degradation of flavoring chemicals in e-cigarettes to aldehydes is statistically insignificant. It is thus important to understand how these molecules react to afford enhanced aerosol products. The purpose of the current study was to investigate the origin of formaldehyde, acrolein, and acetaldehyde in e-cigarettes that contain the popular additive, triacetin (TA). By using 13C labeling and a combination of 1H NMR and 13C NMR, we were able to identify that ester hydrolysis of TA occurs to form acetic acid (HOAc) during aerosolization. The released HOAc acts as a catalyst in the degradation of propylene glycol (PG) and glycerol (GLY), increasing the formation of formaldehyde hemiacetals, acrolein, and acetaldehyde. A solution of 10% TA in 1:1 PG/GLY e-liquid was aerosolized using two different e-cigarettes at two wattages. Each device exhibited a significant increase in aldehyde levels, of up to 185% compared to the aerosol from a 1:1 PG/GLY e-liquid. In addition, the GLY formaldehyde hemiacetal was more predominant within the presence of HOAc, indicating that GLY may be relatively more prone to degradation from protonation.

E-cigarettes can emit formaldehyde at high levels under conditions that have been reported to be non-averse to users.

E-cigarette aerosol emission studies typically focus on benchmarking toxicant levels versus those of cigarettes. However, such studies do not fully account for the distinct chemical makeup of e-liquids and their unique properties. These approaches often conclude that there are fewer and lower levels of toxins produced by e-cigarettes than by cigarettes. In 2015, we reported the discovery of new hemiacetals derived from the reaction of formaldehyde and the e-liquid solvents. The main finding was that they constituted a significant proportion of potentially undetected formaldehyde. Moreover, unlike gaseous formaldehyde, the hemiacetals reside in the aerosol particulate phase, and thus are capable of delivering formaldehyde more deeply into the lungs. However, the findings were criticized by those claiming that some of the results were obtained under conditions that are averse to vapers. A "reinvestigation" of our study was recently published addressing this latter issue. However, this reinvestigation ignored major details, including no mention of the formaldehyde hemiacetals. Herein, we isolated both gaseous formaldehyde and formaldehyde hemiacetals at an intermediate power level claimed, in the "reinvestigation", to be relevant to "non-averse," "normal" usage. The results were that both gaseous formaldehyde and formaldehyde from hemiacetals were produced at levels above OSHA workplace limits.

Dihydroxyacetone levels in electronic cigarettes: Wick temperature and toxin formation.

Recently, we reported the presence of dihydroxyacetone (DHA), the active ingredient in sunless tanners, in the aerosol of an electronic cigarette. DHA has been shown to react with DNA in vitro. The FDA restricts the use of DHA to external application only. It states that it should not be inhaled, ingested, or come into contact with any areas containing mucous membranes, due to unknown risk. Herein, the quantification of DHA in the aerosols of three brands of e-cigarettes has been carried out. These included two devices with horizontal heating coil configurations as well as one with a sub-ohm resistance vertical heating coil. In order to understand and begin to address the origin of DHA and related aerosol products, the wicking properties of the three e-cigarettes were compared. DHA levels were analyzed by a combination of GS/MS and 1H NMR. DHA was found in all three e-cigarettes, with substantially less in the sub-ohm, vertical coil device as compared to the horizontal coil devices (e.g., 0.088 µg/puff vs. 2.29 µg/puff, respectively). Correspondingly, the temperature of the wet layer of the wick for the vertical coil was relatively stable, compared to the wicks for the horizontal coils, upon increasing battery power output. This result is in agreement with prior studies of e-cigarette wicking efficiency and aerosol toxin formation. The temperature measurements reported are a simple means for comparing devices with different design properties during operation.