Multiple-Path Particle Dosimetry Model Research Articles

Contributions of acidic ions in secondary aerosol to PM2.5 bioreactivity in an urban area

Adverse human health effects caused by fine particulate matter (PM2.5) were reported; however, source-specific PM2.5 and its bioreactivity need to be assessed to understand regional human impacts. The objective of this study was to investigate the contributions of PM2.5 to particle bioreactivity in Taichung City, an urban area of west-central Taiwan. The average mass concentration of PM2.5 was 44.4 μg m−3 from 21 March to April 22, 2018. PM2.5 was identified from six distinct sources using a positive matrix factorization (PMF) model. Secondary aerosols were discovered to be the primary contributor to PM2.5 (25.58%), and were primarily composed of Cl−, NO3−, EC, NH4+, and SO42−. It was found that approximately 52.20% (23.2 μg m−3) of inhaled PM2.5 was deposited in the alveolar region after inhalation in the human lungs according to the multiple-path particle dosimetry (MPPD) model. Therefore, human alveolar epithelial A549 cells were exposed to PM2.5, which significantly reduced lung cell viability, and increased the cytotoxic lactate dehydrogenase (LDH), reactive oxygen species (ROS), and inflammatory interleukin (IL)-6 (p < 0.05). Next, we discovered positive correlation between secondary aerosols and ROS production, which was further linked to increases in inorganic ions (Mg2+, Cl−, NO3−, and SO42−) (p < 0.05). In conclusion, acidic ions from secondary aerosols were positively correlated with ROS production in human alveolar epithelial cells. Our results showed that secondary aerosols could be an important determinant of the deterioration of air quality and human respiratory health in urban areas.

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.

Associations between lung-deposited dose of particulate matter and culture-positive pulmonary tuberculosis pleurisy.

Epidemiological studies identified the relationship between air pollution and pulmonary tuberculosis. Effects of lung-deposited dose of particulate matter (PM) on culture-positive pulmonary tuberculosis remain unclear. This study investigates the association between lung-deposited dose of PM and pulmonary tuberculosis pleurisy. A case-control study of subjects undergoing pleural effusion drainage of pulmonary tuberculosis (case) and chronic heart failure (control) was conducted. Metals and biomarkers were quantified in the pleural effusion. The air pollution exposure was measured and PM deposition in the head, tracheobronchial, alveolar region, and total lung region was estimated by Multiple-path Particle Dosimetry (MPPD) Model. We performed multiple logistic regression to examine the associations of these factors with the risk of tuberculosis. We observed that 1-μg/m3 increase in PM10 was associated with 1.226-fold increased crude odds ratio (OR) of tuberculosis (95% confidence interval (CI): 1.023-1.469, p<0.05), 1-μg/m3 increase in PM2.5-10 was associated with 1.482-fold increased crude OR of tuberculosis (95% CI: 1.048-2.097, p < 0.05), 1-ppb increase in NO2 was associated with 1.218-fold increased crude OR of tuberculosis (95% CI: 1.025-1.447, p < 0.05), and 1-ppb increase in O3 was associated with 0.735-fold decreased crude OR of tuberculosis (95% CI: 0.542 0.995). We observed 1-μg/m3 increase in PM deposition in head and nasal region was associated with 1.699-fold increased crude OR of tuberculosis (95% CI: 1.065-2.711, p < 0.05), 1-μg/m3 increase in PM deposition in tracheobronchial region was associated with 1.592-fold increased crude OR of tuberculosis (95% CI: 1.095-2.313, p < 0.05), 1-μg/m3 increase in PM deposition in alveolar region was associated with 3.981-fold increased crude OR of tuberculosis (95% CI: 1.280-12.386, p < 0.05), and 1-μg/m3 increase in PM deposition in total lung was associated with 1.511-fold increased crude OR of tuberculosis (95% CI: 1.050-2.173, p < 0.05). The results indicate that particle deposition in alveolar region could cause higher risk of pulmonary tuberculosis pleurisy than deposition in other lung regions.

Exposure to long-range transported particulate matter and modeling age-related particle deposition.

Exposure to particulate matter (PM) is known to cause cardiovascular disease and increase mortality and morbidity. Asian dust (AD) is a meteorological phenomenon which affects much of East Asia year-round but especially during the spring months. Here, we have characterized concentrations of PM10 and classified synoptic air flow trajectories using HYSPLIT model for Asian dust events (from March to April) in Jeju island, Korea. The ADE is a phenomenon in which sand and dust in the deserts of China or Mongolia rise mainly in spring and are blown away by western winds and gradually subside. The calculated inhaled PM10 doses from specific microenvironments (home, work or school, and transportation) were from 5.28 to 101.48 μg depending on age group and different microenvironments while the calculated PM10 inhaled doses for ADE ranged within 67.92 -769.27 μg. Also, we have evaluated the contribution of specific microenvironments to the exposure for different age groups using time-activity patterns and calculated inhaled PM10 doses and deposited mass/mass flux so as to estimate exposure using multiple-path particle dosimetry (MPPD) model. The monthly average outdoor PM10 concentration range was 29.3-65.4 μg/m3, whereas the monthly PM10 concentration for ADE was 127.0-342.0 μg/m3. Air masses from clusters 1 and 2 were 24% and 29% (in 2017), clusters 2 and 3 were 24% and 32% (in 2018), and clusters 1 and 3 were 28% and 26% (in 2019) for ADE. In the aerosol deposition based on MPPD model, the corresponding values for daily particle deposited mass for two age groups ranged from 8.64 ×10-5 μg (age 8) to 8.64 ×10-4 μg (age 21). We assessed the PM2.5 exposure considering time-activity patterns, age groups, and ADE exposure evaluation caused by long-range transport airflow; this could be helpful for assessing PM10 exposure-related health evaluation.

A Weight-of-the-Evidence Approach for Evaluating, in Lieu of Animal Studies, the Potential of a Novel Polysaccharide Polymer to Produce Lung Overload.

The United States Environmental Protection Agency (EPA) is concerned about the respiratory effects caused by respirable particles of water-insoluble high molecular weight polymers. The EPA has proposed a tiered approach to evaluate polymer lung overload, a kinetic event. Kinetic polymer lung overload in itself is not necessarily adverse, however, inhalation of respirable particulate matter can have adverse effects (i.e., inflammation, fibrosis, etc.). If Tier I testing demonstrates that particles may reach the distal lung (i.e., a non-negligible amount of respirable particles/droplets ≤10 μm in diameter and lack of biosolubility), then animal inhalation testing in Tiers II-IV would be requested. In silico, in chemico, and in vitro alternatives should be considered versus in vivo testing for animal welfare purposes. An in chemico measure of biosolubility was used to demonstrate that a novel α-1,3-glucan polysaccharide, made by enzymatic polymerization of glucose from sucrose, is biosoluble and fits a simple exponential decay model with a half-life on the order of 66 days. The multiple-path particle dosimetry (MPPD) in silico model was used to predict lung burden for the novel α-1,3-glucan polysaccharide. MPPD was validated with measurements in rats exposed to a toner particulate and showed good agreement with lung burden measurements. A simulated 24 month rat exposure yielded 10-20 times less lung burden for the polysaccharide compared to the toner at equivalent exposure concentrations. The MPPD model was refined to include biosolubility data for the polysaccharide polymer. Data for amorphous silica were used to validate the clearance model, and the model incorporating dissolution predicted the amorphous silica lung burden within 20% of measured values. Human equivalent concentrations (HECs) were calculated for each toner rat exposure concentration. HECs were also determined for the polysaccharide at exposure concentrations yielding the same predicted internal doses as the toner. The in vitro, in chemico and in silico studies described here for the novel polysaccharide provide a useful weight of evidence approach in the absence of animal studies for the evaluation of polymer substances where polymer lung overload may be a concern.

Assessment of pedestrian exposure and deposition of PM10, PM2.5 and ultrafine particles at an urban roadside: A case study of Xi'an, China

Assessment of pedestrian exposure and lung deposition is critical to better understanding the health risks resulting from exposure to ambient particles, and to develop site-specific risk control countermeasures. In this study, real-time mobile-monitoring campaigns of three different PM size fractions (PM10, PM2.5 and UFP) were performed during morning and evening peak hours in two seasons (summer and winter), along road sections with differing characteristics (commercial and residential) in Xi'an, China. The Multiple-Path Particle Dosimetry model (MPPD) was utilized to quantify the total and regional depositions for both adults and teens of different genders. Observed PM10, PM2.5 and UFP concentrations showed pronounced regional, seasonal, and diurnal variabilities. The total deposition dose was higher in males than in females for all particle-size fractions in both age groups, except for UFPs in the teen group, the total deposition dose was higher in females. As for regional depositions, these were observed to be highest in the head region, compared with the tracheobronchial and pulmonary regions, regardless of a participant's age or gender. PM10 and PM2.5 showed the highest depositions in the head region for all age groups (PM10: 90%; PM2.5: 67%), while UFP was highly deposited in the pulmonary region (66%). The dominant percentage of UFP deposition in the pulmonary regions strengthens the need to incorporate UFP into the current air-quality index.

Characteristics of indoor air pollutants and estimation of their exposure dose

Rural areas of developing countries have various indoor air pollution sources along with solid fuels used for cooking. This study aims to compare five indoor air pollution sources, viz., incense stick, dhoop, mosquito coil, cigarette, and cooking fuel charcoal, with respect to their pollution potential. The monitoring of PM, CO, CO2, NO2, and particulate bound heavy metals was carried out. Dhoop (DH1) was found to be emitting the highest concentration of metal Sb among all the analyzed metals. Dhoop, incense sticks, mosquito coil, and charcoal were found to be having high pollution potential. The first-order decay rate equation indicated that the highest decay rate constant per hour was observed with dhoop (DH1) for PM10 and PM2.5 and with mosquito coil (M1) for CO. The highest half-life of PM10 and PM2.5 was observed for cigarette (CG1) and charcoal (C1) respectively indicating their slow decay in air. The average daily dose values indicated that the age group 6 to < 11 years, 11 to < 16 years, and 31 to < 51 years will be more vulnerable to PM emissions from dhoop (DH1) and incense stick (IS1). The highest hazard index was estimated for incense stick (IS1) and charcoal. Significant carcinogenic risk was observed from cigarette and charcoal. The multiple-path particle dosimetry (MPPD) model was used to estimate the deposition of PM fractions in various regions of the human body.

Mass dose rates of particle-bound organic pollutants in the human respiratory tract: Implications for inhalation exposure and risk estimations.

To date, little is known about the effective doses of airborne particulate matter (PM) and PM-bound hazardous organic components to the human respiratory tract (HRT). In the light of this, here we provide particle mass dose rates (dose per hour of exposure) of PM and a suite of PM-bound hazardous organic compounds in the HRT for two population age groups (adults & children). More specifically, the mass dose rates of PM and PM-bound polycyclic aromatic hydrocarbons (PAHs), nitrated-PAH (NPAHs), polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs) were estimated at two urban sites using a multiple path particle dosimetry model. We find that, in most cases, the total mass doses are following similar variations across sites and seasons as their ambient total concentrations, however their distribution in the HRT is a function of the particle size distributions and the physiological parameters of each age group. More specifically, the majority of the deposited mass of PM and all the chemical components investigated was accumulated in the upper airways instead of the lungs. We further show that children, due to their different physiology, are more susceptible and receive larger fraction of the total mass doses in the deepest parts of the lungs compared to the adults' group. Comparing the traditional method for estimating the inhalation risk, which is based on the ambient concentration of pollutants, and a modified version using the mass dose in the HRT, we find that the former may overestimate the reported risks. The results presented here provide a novel dataset composed by previously undetermined doses of hazardous airborne particulate organic components in the HRT and demonstrate that alternative health risk estimation approaches may capture some variabilities that are traditionally overlooked.

Translating nanoparticle dosimetry from conventional in vitro systems to occupational inhalation exposures

As encouraged by Toxicity Testing in the 21st Century, researchers increasingly apply high-throughput in vitro approaches to identify and characterize nanoparticle hazards, including conventional aqueous cell culture systems to assess respiratory hazards. Translating nanoparticle dose from conventional toxicity testing systems to relevant human exposures remains a major challenge for assessing occupational risk of nanoparticle exposures. Here, we explored existing computational tools and data available to translate nanoparticle dose metrics from cellular test systems to inhalation exposures of silver nanoparticles in humans. We used the Multiple-Path Particle Dosimetry (MPPD) Model to predict nanoparticle deposition of humans exposed to 20 and 110 nm silver nanoparticles at 0.9 μg/m3 over an 8 h period, the proposed National Institute of Occupational Safety and Health (NIOSH) recommended exposure limit (REL). MPPD predicts 8.1 and 3.7 μg of silver deposited in an 8 h period for 20 and 110 nm nanoparticles, respectively, with 20 nm particles displaying nearly 11-fold higher total surface area deposited. Peak deposited nanoparticle concentrations occurred more proximal in the pulmonary tract compared to mass deposition patterns (generation 4 vs. generations 20–21, respectively) due to regional differences in lung lining fluid volumes. Assuming 0.4% nanoparticle dissolution by mass measured in previous studies predicted peak concentrations of silver ions in cells of 1.06 and 0.89 μg/mL for 20 and 110 nm particles, respectively. Both predicted concentrations are below the measured toxic threshold of 1.7 μg/mL of silver ions in cells from in vitro assessments. Assuming 4% dissolution by mass predicted 10-fold higher silver concentrations in tissues, peaking at 10.6 and 8.9 μg/mL, for 20 and 110 nm nanoparticles respectively, exceeding the observed in vitro toxic threshold and highlighting the importance and sensitivity of dissolution rates. Overall, this approach offers a framework for extrapolating nanotoxicity results from in vitro cell culture systems to human exposures. Aligning appropriate dose metrics from in vitro and in vivo hazard characterizations and human pulmonary doses from occupational exposures are critical components for successful nanoparticle risk assessment and worker protection providing guidance for designing future in vitro studies aimed at relevant human exposures.

Estimating Lung Deposition of Fungal Spores Using Actual Airborne Spore Concentrations and Physiological Data.

Exposure to bioaerosols has been implicated in adverse respiratory symptoms, infectious diseases, and bioterrorism. Although these particles have been measured within residential and occupational settings in multiple studies, the deposition of bioaerosol particles within the human respiratory system has been only minimally explored. This paper uses real-world environmental measurement data of total fungal spores using Air-o-Cell cassettes in 16 different apartments and residents' physiological data in those apartments to predict respiratory deposition of the spores. The airborne spore concentrations were measured during the spring, summer, and fall. The respiratory deposition of five most prevalent spore genera-Ascospores, Aspergillus, Basidiospores, Cladosporium, and Myxomycetes-was predicted using three empirical models: the Multiple Path Particle Dosimetry model, using both the Yeh and age-specific versions, and the Bioaerosol Adaptation of the International Committee on Radiological Protection's Lung deposition model. The predicted total deposited number of spores was highest for Ascospores and Cladosporium. While the majority of spores deposit were in the extrathoracic region, there is a significant deposition for both Aspergillus and Cladosporium in the alveolar region, potentially leading to the development of aspergillosis or allergic asthma. Although the dose-response relationship is unknown, the estimate of the actual spore deposition could be the first step in determining such a relationship.

Characteristics, emission sources and health risk assessment of trace elements in size-segregated aerosols during haze and non-haze periods at Ningbo, China.

To characterize trace elements from inhalable particles and to estimate human health risks, airborne particles at an urban area of Ningbo city during haze and non-haze periods from November 2013 to May 2014 were collected by a nine-stage sampler. Seventeen trace elements (Na, Mg, Al, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Cd and Pb) were measured by inductively coupled plasma mass spectrometry (ICP-MS). The concentrations of trace elements are in the ranges of 0.51ngm-3 (Co) ~ 1.53µgm-3 (K) for fine particles (Dp < 2.1μm), and 1.07ngm-3 (Co) ~ 4.96µgm-3 (K) for coarse particles (2.1μm < Dp < 9.0μm) during the haze days, which are 1.15 -4.30 and 1.23- 7.83-fold as those of non-haze days, respectively. These elements could be divided into crustal elements (Na, Mg, Al, Ca, Ti, Fe and Co), non-crustal elements (Cu, Zn, Cd and Pb) and mixed elements (K, V, Cr, Mn, Ni and As) according to their enrichment factor values (EFs) and size distribution characteristics. Five emission sources of trace elements were identified by positive matrix factorization (PMF) modeling. The main sources of trace elements in fine particles are traffic emission (21.7%), coal combustion (23.6%) and biomass burning (32.1%); however, soil dust (61.5%), traffic emission (21.9%) and industry emissions (11.8%) are the main contributors for coarse particles. With the help of the multiple-path particle dosimetry (MPPD) model, it was found that deposition fractions of seventeen measured elements in the pulmonary region were in the range of 12.4%-15.1% and 6.66% -12.3% for the fine and coarse particles, respectively. The human health risk assessment (HRA) was employed according to the deposition concentration in the pulmonary region. The non-carcinogenic risk (HI) was below the safety limit (1.00). Nonetheless, the excess lifetime carcinogenic risk (ELCR) for adults increased by 2.42-fold during the haze days (2.06 × 10-5) as compared to that of non-haze days (8.50 × 10-6) in fine particles. Cr (VI) and As together contributed 96.5% and 96.3% of the integrated cancer risks during the haze and non-haze periods, respectively. Moreover, the related ELCR values in coarse particles were 36.7% and 62.8% of those in the fine particles for the non-haze period and haze period, respectively.

Modeled Respiratory Tract Deposition of Smoke Aerosol from Conventional Cigarettes, Electronic Cigarettes and Heat-not-burn Products

Knowledge of the deposition of inhaled smoke aerosol in the human respiratory tract has great value for risk assessments of the inhalation toxicology of tobacco products. In this study, differential mobility spectrometry (DMS) was used to characterize smoke particles generated from a conventional cigarette, e-cigarette and heat-not-burn product. The aerosol properties obtained by DMS were then applied to a Multiple Path Particle Dosimetry (MPPD) model to predict the deposition of aerosol particles in the human respiratory tract. The DMS results showed that the particle size distribution of aerosol from the three products differed considerably, with a count median diameter of 14.2–25.4 nm, 50.6–55.3 nm and 172–179 nm for the e-cigarette, heat-not-burn product and conventional cigarette, respectively. However, there was no significant difference in the particle number concentration of aerosol from the three products. The MPPD model indicated that the total deposition fraction of aerosol particles from the e-cigarette and heat-not-burn product was higher than that from the conventional cigarette, and deposition of particles from the e-cigarette in the three human airway regions (head airway, tracheobronchial and pulmonary regions) was higher than that from the heat-not-burn product and conventional cigarette; the particle number concentration deposited in the pulmonary region was the highest, comprising more than 60% of total deposition. Lastly, among the lung lobes, the highest number deposition fraction occurred in the right lower lobe. The relationship between deposition fraction and airway generation was relatively similar among the three aerosols, and the highest deposition fraction occurred in the 20th to 23rd generation airways. The deposition results showed that smaller particles, such as those from the e-cigarette aerosol, were more easily deposited in the human respiratory tract. Combined with knowledge of the harmful aerosol constituents, these deposition data will provide important information for hazard evaluation of new tobacco products.

Quantifying respiratory tract deposition of airborne graphene nanoplatelets: The impact of plate-like shape and folded structure

The booming development of commercial products containing graphene nanoplatelets (GNPs) triggers growing concerns over their release into the air. Precise prediction of human respiratory system deposition of airborne GNPs, especially in alveolar region, is very important for inhalation exposure assessment. In this study, the pulmonary deposition of airborne GNPs was predicted by the multiple-path particle dosimetry (MPPD) model with consideration of GNPs plate-like shape and folded structure effect. Different equivalent diameters of GNPs were derived and utilized to describe different deposition mechanisms in the MPPD model. Both of small GNPs (geometric lateral size dg < 0.1 μm) and large GNPs (dg > 10 μm) had high deposition fractions in human respiratory system. The total deposition fractions for 0.1 and 30 μm GNPs were 41.6% and 75.6%, respectively. Most of the small GNPs deposited in the alveolar region, while the large GNPs deposited in the head airways. The aerodynamic diameter of GNPs was much smaller than the geometric lateral dimension due to the nanoscale thickness. For GNPs with geometric lateral size of 30 μm, the aerodynamic diameter was 2.98 μm. The small aerodynamic diameter of plate-like GNPs enabled deposition in the alveolar region, and folded GNPs had higher alveolar deposition than planar GNPs. Heavy breathing led to higher GNPs deposition fraction in head airways and lower deposition fractions in the alveolar region than resting breathing.

Size distributions of particle-generated hydroxyl radical (·OH) in surrogate lung fluid (SLF) solution and their potential sources.

Although it is known that increases in ambient particulate matter (PM) levels are associated with elevated occurrence of adverse health outcomes, the understanding of the mechanisms of PM-related health effects is limited by our knowledge of how particle size and composition are altered subsequent to inhalation through respiratory-deposited processing. Here we present a particle-generated hydroxyl radical (·OH) study of the size-resolved particles as particles are inhaled in the human respiratory tract (RT), and we show that accumulation-mode particles are significant factors (71-75%) in ·OH generation of lung-deposited particles using Multiple-Path Particle Dosimetry (MPPD) model. The ability of PM to catalyze ·OH generation is mainly related to transition metals, particularly towards the upper regions of the RT (75%), and to quinones deeper in the lung (42-46%). Identification of this generation ability induced by chemical composition has shown that four potential sources (biomass burning, incomplete combustion, mobile & industry, and mineral dust) are responsible for ·OH generation. With ·OH-forming ability after PM inhalation implicated as the first step towards revealing the subsequent toxic processes, this work draws a connection between the detailed ·OH chemistry occurring on size-resolved particles and a possible toxicological mechanism based on chemical composition and sources.

Efficient bi-directional coupling of 3D computational fluid-particle dynamics and 1D Multiple Path Particle Dosimetry lung models for multiscale modeling of aerosol dosimetry

The development of predictive aerosol dosimetry models has been a major focus of environmental toxicology and pharmaceutical health research for decades. One-dimensional (1D) models successfully predict overall deposition averages but fail to accurately predict local deposition. Computational fluid-particle dynamics (CFPD) models provide site-specific predictions but at a computational cost that prohibits whole lung predictions. Thus, there is a need for developing multiscale strategies to provide a realistic subject-specific picture of the fate of inhaled aerosol in the lungs. CT-based 3D/CFPD models of the large airways were bidirectionally coupled with individualized 1D Navier-Stokes airflow and particle transport based upon the widely used Multiple Path Particle Dosimetry Model (MPPD). Distribution of airflows among lobes was adjusted by measured lobar volume changes observed in CT images between FRC and FRC +1.5 L. As a test of the effectiveness of the coupling procedures, deposition modeling of previous 1 μm aerosol exposure studies was performed. The complete coupled model was run for 3 breaths, with the computation-intense portion being the 3D CFPD Lagrangian particle tracking calculation. The average deposition per breath was 11% in the combined multiscale model with site-specific doses available in the CFPD portion of the model and airway- or region-specific deposition available for the MPPD portion. In conclusion, the key methods developed in this study enable predictions of ventilation heterogeneities and aerosol deposition across the lungs that are not captured by 3D or 1D models alone. These methods can be used as the foundation for multi-scale modeling of the full respiratory system.

Toxic trace metals in size-segregated fine particulate matter: Mass concentration, respiratory deposition, and risk assessment

To characterise the mass concentration, size-distribution, and respiratory deposition of selected trace metals (Cr, Mn, Fe, Ni, Cu, Zn, Ba, and Pb) in size-segregated PM2.5, a long-term monitoring campaign was undertaken at an urban background site in Como (Northern Italy). 96-h aerosol samples were collected weekly, from May 2015 to March 2016, using a 13-stage low pressure impactor and analysed via laser ablation-inductively coupled plasma-mass spectrometry. Significantly higher levels of trace metals were generally found during the heating season (two to more than four times) compared to the non-heating period at all size ranges, especially for concentrations in PM0.1–1. Distinct distribution profiles characterised the different elements, even though the corresponding heating and non-heating shapes always exhibited similar features, with negligible seasonal shifts in the average mass median aerodynamic diameters. Fe, Ba, and Cu had >70% of their mass in PM1–2.5, whereas Pb, Zn, and Ni showed higher contributions in the accumulation mode (>60%). Finally, broad size-distributions were found for Cr and Mn. The multiple-path particle dosimetry model estimated the overall deposition fractions in human airways varying between 27% (Pb) and 48% (Ba). The greatest deposition variability was always registered in the head region of the respiratory system, with the highest contributions for those metals predominantly accumulated in the PM2.5 coarse modes. In contrast, the deposition in the deepest respiratory tract maintained nearly constant proportions over time, becoming notably important for Pb, Ni, and Zn (∼13%) with respect to their total deposition. The comparison with national limits established for Pb and Ni suggested the absence of significant risks for the local population, as expected, with average concentrations two orders of magnitude lower than the corresponding annual limit and objective value. Similar findings were reported for all the other metals, for which the estimated hazard quotients were always well <1.

Relationship between Aerosols Exposure and Lung Deposition Dose

We conducted a systematic study to evaluate the relationship of exposure to aerosols with specific focus on airborne ultrafine particles and the effective dose in the lungs of humans or animals. By multiplying particle concentration size distributions with lung deposition curves of the Multiple-Path Particle Dosimetry (MPPD) model, the lung deposition concentrations, which could be directly linked to the effective dose via inhalation rate and exposure time, were estimated. The calculations were performed on a number of representative particle size distributions ex-tracted from measurement data in the literature. Apart from the evaluation of the lung depos-ited particle concentration, we investigated whether and how the lung deposited particle con-centration depended on the diameter of the main mode of the considered size distribution and if there was a potential animal surrogate for human beings in inhalation exposure studies. The average deep-lung deposited fraction (sum of alveolar and trachea-bronchial deposited concentrations divided by the ambient concentration) depended on the inhaled aerosol size distribution and the considered metric (number, surface area or mass). It was slightly higher in terms of number than for surface area and mass. Moreover, the lung deposited particle frac-tion depended also on the diameter of the main mode of the inhaled aerosol size distribution: the smaller the diameter of the main mode, the higher the lung deposited particle fraction. Our study aims at a better understanding of the correlations between the particle parameters meas-ured in exposure studies and the dose metrics in the lung, which in turn facilitates the risk as-sessment of ambient ultrafine particles.

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.

Distribution, characterization and health risk assessment of size fractionated bioaerosols at an open landfill site in Dehradun, India

Open landfilling is a common practice of waste dumping in developing countries, generating a range of environmental and public health hazards. In this study, we determined the distribution, composition and exposure risk of the size-segregated fungal and bacterial bioaerosols in an open landfill site in Dehradun, India. Bioaerosol and particulate matter (PM) measurements were carried out using a six-stage viable Andersen Cascade Impactor and a Wide Range Aerosol Spectrometer, respectively. Pearson correlation analysis was used to determine the relation of bioaerosol concentration with meteorological parameters and PM. The mean concentration of fungal and bacterial aerosols was observed to be 4582.75 ± 1358.25 CFU/m3 and 3609.53 ± 1000.28 CFU/m3, respectively. The bioaerosol composition showed the predominance of potential pathogens including Aspergillus (25.42%), Penicillium (20.34%), Cladosporium (15.25%), Alternaria (13.56%); and gram-negative Bacillus (21.15%), Streptobacillus (17.31%), Coccus (13.46%). Also, an inhalation risk assessment was conducted for the age-specific predictions of bioaerosol and PM deposition in human airways using a multiple path particle dosimetry model. For bioaerosols, maximum submicron depositions in the pulmonary region were observed in adults, while for PM, in children and infants. Finally, to identify the bioaerosol exposure caused respiratory disorders, a questionnaire-based health survey was conducted among the exposed population around the landfill site. The chi-square test showed significantly higher respiratory complaints in females for cold, cough, chest pain and chest tightness than in males. This work highlights the role of bioaerosols and PM in human health disorders in occupational environments associated with waste management.

A 21-day sub-acute, whole-body inhalation exposure to printer-emitted engineered nanoparticles in rats: Exploring pulmonary and systemic effects

Engineered nanomaterials (ENMs) used in toners to improve their performance are released in the air during laser printer use. ENMs play an important catalytic role in the breakdown of the toner polymer and subsequent rearrangement of organic compounds as well as in the formation of reactive oxygen species (ROS). Cellular, animal, and human occupational exposure studies have shown that such printer-emitted particles (PEPs) induce inflammation, systemic oxidative stress, and genotoxicity, as well as, increase frequency of coughing, wheezing, and upper airway symptoms, raising concerns about their long-term impact on human health. No safety thresholds or regulatory guidelines currently exist for PEPs. In this study, Sprague-Dawley rats were exposed (by whole-body inhalation) to PEPs 5 h/day for up to 21 days using an exposure platform previously developed by the authors. The control group comprised of an equal number of rats exposed to high-efficiency particulate air (HEPA) filtered air. The PEPs had a mean particle diameter of approximately 45 nm, and a total particle number concentration ranging from 4 to 21 × 105 #/cm3. The maximum total volatile organic compound (tVOCs) concentration was 363.2 ± 162 ppb. The Multiple-Path Particle Dosimetry Model (MPPD) estimated the deposited fraction of PEPs to be around 7, 6 and 21% in the head, tracheobronchial (TB) and alveolar regions, respectively. Analysis of biochemical markers in the nasal and bronchoalveolar lavage fluids (NLF, BALF) of PEPs-exposed animals showed only mild oxidative stress and inflammation. No damage was detected in the histological and chemiluminescence analysis of lung and heart tissues of PEPs-exposed animals. Pro- and anti-inflammatory cytokines and chemokines, such as Interleukin (IL) 1β, IL-12, IL-18, MIP-1α, MIP-2, GRO/KC, and Fractalkine were found to be up-/down-regulated in NLF and BALF of the PEPs-exposed animals. Also, serum biomarkers of oxidative stress and inflammation, such as 8-isoprostane, 4-hydroxynonemal, and Leukotriene B4 were elevated in PEPs-exposed animals. In conclusion, following exposure to PEPs, there was modest lung injury and inflammation in the respiratory tract. Specifically, changes in expression of certain cytokines and chemokines, along with serum levels of 8-isoprostane, were the most significant adverse effects reported following exposure to PEPs.