Modeled Respiratory Tract Deposition of Aerosolized Oil Diluents Used in Δ9-THC-Based Electronic Cigarette Liquid Products

Electronic cigarette, or vaping, products (EVP) heat liquids (“e-liquids”) that contain substances (licit or illicit) and deliver aerosolized particles into the lungs. Commercially available oils such as Vitamin-E-acetate (VEA), Vitamin E oil, coconut, and medium chain triglycerides (MCT) were often the constituents of e-liquids associated with an e-cigarette, or vaping, product use-associated lung injury (EVALI). The objective of this study was to evaluate the mass-based physical characteristics of the aerosolized e-liquids prepared using these oil diluents. These characteristics were particle size distributions for modeling regional respiratory deposition and puff-based total aerosol mass for estimating the number of particles delivered to the respiratory tract. Four types of e-liquids were prepared by adding terpenes to oil diluents individually: VEA, Vitamin E oil, coconut oil, and MCT. A smoking machine was used to aerosolize each e-liquid at a predetermined puff topography (volume of 55 ml for 3 s with 30-s intervals between puffs). A cascade impactor was used to collect the size-segregated aerosol for calculating the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD). The respiratory deposition of EVP aerosols on inhalation was estimated using the Multiple-Path Particle Dosimetry model. From these results, the exhaled fraction of EVP aerosols was calculated as a surrogate of secondhand exposure potential. The MMAD of VEA (0.61 μm) was statistically different compared to MCT (0.38 μm) and coconut oil (0.47 μm) but not to Vitamin E oil (0.58 μm); p < 0.05. Wider aerosol size distribution was observed for VEA (GSD 2.35) and MCT (GSD 2.08) compared with coconut oil (GSD 1.53) and Vitamin E oil (GSD 1.55). Irrespective of the statistical differences between MMADs, dosimetry modeling resulted in the similar regional and lobular deposition of particles for all e-liquids in the respiratory tract. The highest (~0.08 or more) fractional deposition was predicted in the pulmonary region, which is consistent as the site of injury among EVALI cases. Secondhand exposure calculations indicated that a substantial amount of EVP aerosols could be exhaled, which has potential implications for bystanders. The number of EVALI cases has declined with the removal of VEA; however, further research is required to investigate the commonly available commercial ingredients used in e-liquid preparations.

PREDICTION OF AEROSOL PARTICLE SIZE DISTRIBUTION FROM THE MEAS-URED VALUES OF PM2.5 AND PM10

Introduction. Ambient air pollution with particulate matter from various sources sig-nificantly increases the risk of human health disorders. The concentrations of the total suspended particles (TSP), as well as the PM2.5 and PM10 fractions, are mainly monitored. In fact, the ac-tual size distribution of aerosol particles differs significantly from the stepwise distribution formed only by the concentrations of PM2.5 and PM10. Aim of the study: development of a method for reconstructing the size distribution function of aerosol particles from the actual concentrations of PM2.5 and PM10 under the assumption of a lognormal size distribution for calculation of doses deposited in different lung regions. Methods. Long-term concentrations of various fractions of particles in the ambient air were ob-tained from the database of social and hygienic monitoring created by the "Center for Hygiene and Epidemiology in the Republic of Tatarstan (Tatarstan)". A reconstructed theoretical particle size distribution function f0(dp) was derived using the numerical solution, and the corresponding software was developed. The MPPD (Multiple-Path Particle Dosimetry) software was used to calculate the particle deposited doses in different areas of the human respiratory tract. Results. The measured values of the PM2.5 and PM10 concentrations were used to derive the lognormal aerosol size distribution. Based on the calculation of the mass doses of settled particles in the human respiratory system using MPPD (Multiple-Path Particle Dosimetry) code, it is shown that the calculation based only on the values of PM2.5 and PM10 leads to an underestimation of the mass fractions of particles in the lower respiratory tract and alveolar zone, the values of which are determinant for the estimation of the risk of lung disease. Conclusions. The proposed method for reconstructing the size distribution function of the con-centration of aerosol particles is important for a quantitatively reliable assessment of the risks of exposure to ambient air aerosols, making it possible to move from assessment of external expo-sures to the calculation of deposited fractions. The use of deposited fractions as an exposure pa-rameter increases the accuracy of health risk assessments associated with particulate matter ex-posure. This approach can be used both in the study of ambient aerosols and for the air of the working area.

A whole lung in silico model to estimate age dependent particle dosimetry

Anatomical and physiological changes alter airflow characteristics and aerosol distribution in the developing lung. Correlation between age and aerosol dosimetry is needed, specifically because youth are more susceptible to medication side effects. In this study, we estimate aerosol dosages (particle diameters of 1, 3, and 5 $$\upmu$$ μ m) in a 3 month-old infant, a 6 year-old child, and a 36 year-old adult by performing whole lung subject-specific particle simulations throughout respiration. For 3 $$\upmu$$ μ m diameter particles we estimate total deposition as 88, 73, and $$66\%$$ 66 % and the conducting versus respiratory deposition ratios as 4.0, 0.5, and 0.4 for the infant, child, and adult, respectively. Due to their lower tidal volumes and functional residual capacities the deposited mass is smaller while the tissue concentrations are larger in the infant and child subjects, compared to the adult. Furthermore, we find that dose cannot be predicted by simply scaling by tidal volumes. These results highlight the need for additional clinical and computational studies that investigate the efficiency of treatment, while optimizing dosage levels in order to alleviate side effects, in youth.

Fluid Menisci and In Vitro Particle Dosimetry of Submerged Cells

Understanding the mechanisms of interaction between cells and particulate nanomaterials lies in the heart of assessing the hazard associated with nanoparticles. The paradigm of toxicology requires quantifying and interpreting dose-response relationships, and cells cultured in vitro and exposed to particle dispersions rely on mathematical models that estimate the received nanoparticle dose. Yet, none of these models acknowledges the fact that aqueous cell-culture media wet the inner surface of hydrophilic open wells, which results in curved fluid-air interface called meniscus. We show that omitting this phenomenon leads to a nontrivial but systematic error and twists the fundamental concept of nanotoxicology. Given that reproducibility and harmonization between meta analyses, in vitro, in silico, and in vivo studies must be improved, we present an adequate mathematical model that greatly advances such efforts.

Oxidative Potential Associated with Urban Aerosol Deposited into the Respiratory System and Relevant Elemental and Ionic Fraction Contributions

Size-segregated aerosol measurements were carried out at an urban and at an industrial site. Soluble and insoluble fractions of elements and inorganic ions were determined. Oxidative potential (OP) was assessed on the soluble fraction of Particulate Matter (PM) by ascorbic acid (AA), dichlorofluorescein (DCFH) and dithiothreitol (DTT) assays. Size resolved elemental, ion and OP doses in the head (H), tracheobronchial (TB) and alveolar (Al) regions were estimated using the Multiple-Path Particle Dosimetry (MPPD) model. The total aerosol respiratory doses due to brake and soil resuspension emissions were higher at the urban than at the industrial site. On the contrary, the doses of anthropic combustion tracers were generally higher at the industrial site. In general, the insoluble fraction was more abundantly distributed in the coarse than in the fine mode and vice versa for the soluble fraction. Consequently, for the latter, the percent of the total respiratory dose deposited in TB and Al regions increased. Oxidative potential assay (OPAA) doses were distributed in the coarse region; therefore, their major contribution was in the H region. The contribution in the TB and Al regions increased for OPDTT and OPDCFH.

Derivation of occupational exposure limits for multi-walled carbon nanotubes and graphene using subchronic inhalation toxicity data and a multi-path particle dosimetry model

In this study, we aimed to provide the recommended occupational exposure limits (OELs) for MWCNTs and graphene nanomaterials based on data from a subchronic inhalation toxicity study using a lung dosimetry model.