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Background: Marijuana blunts, which are tobacco cigar wrappers filled with marijuana, are commonly smoked in the US as a means of cannabis use. The use of marijuana blunts presents toxicity concerns because the smoke contains both marijuana-related and tobacco-related chemicals. Thus, it is important to understand the chemical composition of mainstream smoke (MSS) from marijuana blunts. This study demonstrates the ability to detect and identify chemical constituents exclusively associated with blunt MSS in contrast to tobacco cigar MSS (designated as 'new exposures') through non-targeted chemical analysis. Methods: Samples collected separately from blunt MSS and tobacco cigar MSS were analyzed using two-dimensional gas chromatography-time-of-flight mass spectrometry (GC × GC-TOFMS). Results and Discussion: Two new exposures, which likely represent only a subset of all new exposures, were identified by evaluating the data from thousands of detected signals and then confirming selected compound identities in analyses using authentic chemical standards. The two confirmed new exposures, mellein and 2-phenyl-2-oxazoline, are not cannabinoids and, to the best of our knowledge, have not been previously reported in association with cannabis, tobacco, or smoke of any kind. In addition, we detected and quantified three phenols (2-, 3-, and 4-ethylphenol) in blunt MSS. Given the toxicity of phenols, quantifying the levels of other phenols could be pursued in future research on blunt MSS. Conclusion: This study shows the power and utility of GC × GC-TOFMS as a methodology for non-targeted chemical analysis to identify new chemical exposures in blunt MSS and to provide data to guide further investigations of blunt MSS.

Objective: Most studies report that inhaled volatile and semivolatile organic compounds (VOCs/SVOCs) tend to deposit in the upper respiratory tract, while ultrafine (or near ultrafine) particulate matter (PM) (∼100 nm) reaches the lower airways. The objective of this study was to determine whether carbon particle co-exposure carries VOCs/SVOCs deeper into the lungs where they are deposited., Materials and Methods: Male Sprague-Dawley rats were exposed by inhalation (nose-only) to radiolabeled toluene (20 ppm) or naphthalene (20 ppm) on a single occasion for 1 h, with or without concurrent carbon particle exposure (∼5 mg/m 3 ). The distribution of radiolabel deposited within the respiratory tract of each animal was determined after sacrifice. The extent of adsorption of toluene and naphthalene to airborne carbon particles under the exposure conditions of the study was also assessed., Results: We found that in the absence of particles, the highest deposition of both naphthalene and toluene was observed in the upper respiratory tract. Co-exposure with carbon particles tended to increase naphthalene deposition slightly throughout the respiratory tract, whereas slight decreases in toluene deposition were observed. Few differences were statistically significant. Naphthalene showed greater adsorption to the particles compared to toluene, but overall the particle-adsorbed concentration of each of these compounds was a small fraction of the total inspired concentration., Conclusions: These studies imply that at the concentrations used for the exposures in this study, inhaled carbon particles do not substantially alter the deposition of naphthalene and toluene within the respiratory tract.

Comparing effects of inhaled particles across rodent test systems and between rodent test systems and humans is a key obstacle to the interpretation of common toxicological test systems for human risk assessment. These comparisons, correlation with effects and prediction of effects, are best conducted using measures of tissue dose in the respiratory tract. Differences in lung geometry, physiology and the characteristics of ventilation can give rise to differences in the regional deposition of particles in the lung in these species. Differences in regional lung tissue doses cannot currently be measured experimentally. Regional lung tissue dosimetry can however be predicted using models developed for rats, monkeys, and humans. A computational model of particle respiratory tract deposition and clearance was developed for BALB/c and B6C3F1 mice, creating a cross-species suite of available models for particle dosimetry in the lung. Airflow and particle transport equations were solved throughout the respiratory tract of these mice strains to obtain temporal and spatial concentration of inhaled particles from which deposition fractions were determined. Particle inhalability (Inhalable fraction, IF) and upper respiratory tract (URT) deposition were directly related to particle diffusive and inertial properties. Measurements of the retained mass at several post-exposure times following exposure to iron oxide nanoparticles, micro- and nanoscale C60 fullerene, and nanoscale silver particles were used to calibrate and verify model predictions of total lung dose. Interstrain (mice) and interspecies (mouse, rat and human) differences in particle inhalability, fractional deposition and tissue dosimetry are described for ultrafine, fine and coarse particles.