Multiple-Path Particle Dosimetry Research Articles

A new approach for risk assessment of pulmonary toxicants: a preliminary study using didecyldimethylammonium chloride.

Current human risk assessments often rely on animal toxicity data to establish point of departure (POD) values, followed by the application of uncertainty factors. Consequently, there is growing interest in alternative toxicity testing methods that reduce reliance on animal models. In this study, we propose a novel approach for inhalation toxicity risk assessment that integrates in silico and in vitro methods. Human primary alveolar epithelial cells were exposed to aerosolized didecyldimethylammonium chloride (DDAC) to assess cytotoxicity. This was followed by transcriptome analysis and biological pathway investigation, utilizing adverse outcome pathway (AOP), to calculate the POD. Additionally, human DDAC exposure was simulated using a multiple-path particle dosimetry (MPPD) model to predict exposure levels in the human alveolar region via inhalation. The results from in silico and in vitro studies were then compared, and a comprehensive risk assessment was performed. The POD for AOP 452 key events-oxidative stress, inflammation, epithelial-mesenchymal transition (EMT), apoptosis, and autophagy-was found to range between 19.0 and 23.89ng/cm2, according to benchmark dose calculation tools. The estimated human exposure to DDAC in the alveolar region under actual exposure conditions was 0.164ng/cm2/day, resulting in a margin of exposure (MOE) ranging from 121 to 145, suggesting caution regarding DDAC inhalation exposure. This study presents a novel risk assessment method that compares estimated human inhalation exposure values to in vitro results, applying the human equivalent concentration concept. Our findings demonstrate the potential for conducting human risk assessments using both in silico and in vitro methods as alternatives to traditional in vivo studies.

Influence of agricultural activity in corn farming on airborne microplastic in surrounding elementary school

Microplastics (MPs) have been widely detected in agricultural soils, and agricultural activities have been identified as an important factor influencing the abundance of MPs in the air. However, no studies have investigated whether agricultural activities are contributors to airborne MPs in buildings near farms. We collected airborne MP samples using an active sampling method from an elementary school near corn farms during different cultivation stages to assess the impact of agricultural activities on MPs in the study school near farms. Our data showed that the predominant shapes, sizes, colors, and polymer compositions were fragments, 2–50 μm, black or grey, and polyethylene terephthalate, respectively, during all cultivation stages. The highest and lowest MP concentrations were recorded during the land preparation (56.8 ± 7.4 particles/m3, August 2022) and growth (2.5 ± 1.8 particles/m3, February 2022) stages, respectively. A multiple-path particle dosimetry model revealed that the deposition fractions of MPs in humans were highest in the head; the highest and lowest deposition rates and fluxes of MPs in the airway were found during the land preparation and growth stages, respectively. The concentration of MPs did not present a positive correlation with potassium or crustal elemental concentration; however, it did show a positive association with temperature value. Therefore, our data did not show that corn cultivation influences MP concentrations in the study school near corn farms; instead, temperature was an important influencing factor.

Seasonal variation in exposure to particulate matter among children attending different levels of education: Comparison of two dosimetry models

Exposure to particulate matter (PM) has been associated with several adverse health outcomes. Studies indicate that children may be exposed to much higher concentrations of PM at school than in other environments. There exists very little data on the deposited dose of PM while children attend classes. This study was carried out in a school located near an industrial complex in Portugal and attended by children aged 3–12 years. Indoor PM10, PM2.5 and PM1 were measured over two seasons in classrooms representing different school year groups. Particle deposition fractions in the respiratory tract, as well as the deposited doses, were calculated using the Multiple-Path Particle Dosimetry (MPPD) and the Exposure Dose Model (ExDoM2). Both models were implemented assuming an 8-h exposure scenario to represent the school day. In general, differences in PM concentrations were observed depending on room occupancy periods and season. The highest mean PM2.5 concentration was recorded in winter when the classroom was vacant (23.7 ± 20.5 μg m−3), while the highest mean PM10 level was observed in spring during school hours (61.7 ± 24.2 μg m−3). Regardless of the dosimetry model, the highest deposition of PM10 and PM2.5 was in the upper region, while the lowest was in the tracheobronchial (TB) region. The results indicate that deposited dose and deposition fraction in spring may be more harmful to pupils’ health than in winter. PM10 presented the highest doses, ranging from 54.2 to 128 μg and from 83.9 to 185 μg, according to MPPD and ExDoM2 estimates, respectively.

Use of quantitative in vitro to in vivo extrapolation (QIVIVE) for the assessment of non-combustible next-generation product aerosols.

With the use of in vitro new approach methodologies (NAMs) for the assessment of non-combustible next-generation nicotine delivery products, new extrapolation methods will also be required to interpret and contextualize the physiological relevance of these results. Quantitative in vitro to in vivo extrapolation (QIVIVE) can translate in vitro concentrations into in-life exposures with physiologically-based pharmacokinetic (PBPK) modelling and provide estimates of the likelihood of harmful effects from expected exposures. A major challenge for evaluating inhalation toxicology is an accurate assessment of the delivered dose to the surface of the cells and the internalized dose. To estimate this, we ran the multiple-path particle dosimetry (MPPD) model to characterize particle deposition in the respiratory tract and developed a PBPK model for nicotine that was validated with human clinical trial data for cigarettes. Finally, we estimated a Human Equivalent Concentration (HEC) and predicted plasma concentrations based on the minimum effective concentration (MEC) derived after acute exposure of BEAS-2B cells to cigarette smoke (1R6F), or heated tobacco product (HTP) aerosol at the air liquid interface (ALI). The MPPD-PBPK model predicted the in vivo data from clinical studies within a factor of two, indicating good agreement as noted by WHO International Programme on Chemical Safety (2010) guidance. We then used QIVIVE to derive the exposure concentration (HEC) that matched the estimated in vitro deposition point of departure (POD) (MEC cigarette = 0.38 puffs or 11.6µg nicotine, HTP = 22.9 puffs or 125.6µg nicotine) and subsequently derived the equivalent human plasma concentrations. Results indicate that for the 1R6F cigarette, inhaling 1/6th of a stick would be required to induce the same effects observed in vitro, in vivo. Whereas, for HTP it would be necessary to consume 3 sticks simultaneously to induce in vivo the effects observed in vitro. This data further demonstrates the reduced physiological potency potential of HTP aerosol compared to cigarette smoke. The QIVIVE approach demonstrates great promise in assisting human health risk assessments, however, further optimization and standardization are required for the substantiation of a meaningful contribution to tobacco harm reduction by alternative nicotine delivery products.

Size Distributions and Health Risks of Particulate Polycyclic Aromatic Hydrocarbons in the Atmosphere at Coastal Areas in Ningbo, China.

Most current research focusing on the health risk assessments of particulate polycyclic aromatic hydrocarbons (PAHs) have not analyzed the size distributions and human respiratory deposition rates. In the present study, size-separated particulate matter (PM) was collected in the coastal area of Ningbo using an Anderson eight-stage air sampler over a 1-year period (2014-2015). The 16 US Environmental Protection Agency priority PAHs associated with PM were pretreated with rapid solvent extraction and analyzed by gas chromatography-mass spectrometry. The respiratory exposure assessment was determined using the multiple-path particle dosimetry (MPPD) model. The results show that all PAHs exhibited bimodal distribution with one mode peak in accumulation mode (0.43-0.65 µm) and another mode peak in coarse mode (4.7-5.8 µm). In addition, a low coefficient of divergence of PAHs between PM2.1 and PM2.1-10 indicated a high spatial heterogeneity in source factor contribution and formation mechanism. The deposition fluxes (tracheobronchial + pulmonary) of PM were highest for children in the size range of 3.3 µm < particle diameter (Dp) < 9 µm, while for males and females the highest fluxes occurred in the size range of 1.1 µm < Dp < 2.1 µm. The depositions of coarse PM in children were significantly higher than those in adults. The benzo[a]pyrene equivalent (BaPeq) depositions of dibenz[a,h]anthracene ranged from 1.4e-04 to 0.015 ng h-1, which were highest among the PAHs. The PAHs on particles with Dp >4.7 µm contributed approximately three times more to children than to males and females. Therefore, the toxicity of coarse PM to children needed attention. The incremental lifetime cancer risks (ILCR) for children, males, and females were estimated to be 2.92 × 10-7, 1.82 × 10-7, and 2.38 × 10-7, respectively, which were below the cancer risk guideline value (10-6). These ILCR values were much lower than the risks calculated without considering particle size distributions and respiratory depositions. The combination of the size-segregated sampling technique and the MPPD model can effectively avoid the overestimation of human respiratory exposure. Environ Toxicol Chem 2024;43:1364-1377. © 2024 SETAC.

Effective density of inhaled environmental and engineered nanoparticles and its impact on the lung deposition and dosimetry

BackgroundAirborne environmental and engineered nanoparticles (NPs) are inhaled and deposited in the respiratory system. The inhaled dose of such NPs and their deposition location in the lung determines their impact on health. When calculating NP deposition using particle inhalation models, a common approach is to use the bulk material density, ρb, rather than the effective density, ρeff. This neglects though the porous agglomerate structure of NPs and may result in a significant error of their lung-deposited dose and location.ResultsHere, the deposition of various environmental NPs (aircraft and diesel black carbon, wood smoke) and engineered NPs (silica, zirconia) in the respiratory system of humans and mice is calculated using the Multiple-Path Particle Dosimetry model accounting for their realistic structure and effective density. This is done by measuring the NP ρeff which was found to be up to one order of magnitude smaller than ρb. Accounting for the realistic ρeff of NPs reduces their deposited mass in the pulmonary region of the respiratory system up to a factor of two in both human and mouse models. Neglecting the ρeff of NPs does not alter significantly the distribution of the deposited mass fractions in the human or mouse respiratory tract that are obtained by normalizing the mass deposited at the head, tracheobronchial and pulmonary regions by the total deposited mass. Finally, the total deposited mass fraction derived this way is in excellent agreement with those measured in human studies for diesel black carbon.ConclusionsThe doses of inhaled NPs are overestimated by inhalation particle deposition models when the ρb is used instead of the real-world effective density which can vary significantly due to the porous agglomerate structure of NPs. So the use of realistic ρeff, which can be measured as described here, is essential to determine the lung deposition and dosimetry of inhaled NPs and their impact on public health.Graphical abstract

Estimates of Inhaled and Deposited Doses following Exposure to Humidifier Disinfectant Containing Polyhexamethylene Guanidine (PHMG)

We estimated the inhaled and deposited dose in humans using the International Commission on Radiological Protection (ICRP) and multiple-path particle dosimetry (MPPD) models following exposure to humidifier disinfectant containing polyhexamethylene guanidine (PHMG). The disinfectant has caused at least 1,810 deaths, with an odds ratio of lung injury of 47.3 (95% confidence interval: 6.1–369.7), because of its application in Korea. In this study, the Oxy product, which is regarded as the causative agent of most lung diseases, was sprayed into a cleanroom at normal (6.5 ppm in solution) and worst case (65 ppm in solution) dilutions; the airborne aerosol was monitored with direct reading instruments. Areas of deposition were divided into the head airway, tracheobronchial, and alveolar regions. Four dose scenarios were considered in this study: adults and children in both daily average and sleep conditions. Most PHMG aerosols were smaller than PM1 (96%). Number-based concentration analysis showed that &lt;100 nm nanoparticles comprised 81% and 69% of the aerosol when the 6.5 and 65 ppm solutions were used, respectively. In all scenarios, the number-based deposited dose increased in the order of alveolar, tracheobronchial, and head airway regions; the mass-based deposited dose increased in the order of the head airway, alveolar, and tracheobronchial regions. The deposited dose per unit body weight was higher in children than in adults in terms of both number- and mass-based concentrations. When the humidifier was sprayed, the highest number-based concentration was found at a particle size of 15.4 nm; the highest deposition fraction or dose by PM1 was observed in the pulmonary and head airways in both models.

Investigating the temporal dynamics of sub-micron particles and particle-bound transition metals in indoor air of a metropolitan city.

The present study portrays an association between particle-bound transition metals and children's health. The indoor air quality of the urban metropolitan city households was monitored for four PM sizes, namely PM1.0-2.5, PM0.50-1.0, PM0.25-0.50 and PM<0.25, in major seasons observed in the city; summer and winter. Further transition/heavy metals, viz. Cr, Cu, Fe, Mn, Ni, Pb and Zn, were analysed in PM1-2.5 samples. In order to evaluate the effect, health risk assessment was performed using mathematical and computational model for assessing dermal exposure and dose estimation (multiple path particle dosimetry model version3.0). The study principally targeted the children aged 2-15years for the health risk assessment. According to the results, for the largest particle size i.e. PM1.0-2.5 the highest deposition was in the head region (49.1%) followed by pulmonary (43.6%) and tracheobronchial region (7.2%), whereas, for the smallest particle size i.e. PM<0.25 the highest deposition was obtained in the pulmonary region (73.0%) followed by the head (13.6%) and TB region (13.2%). Also, the most imperilled group of children with highest dose accumulation was found to be children aged 8-9years for all particle sizes. Moreover, the dermal exposure dose as evaluated was found to be preeminent for Ni, Zn and Pb. Besides, seasonal variation gesticulated towards elevated concentrations in winter relative to the summer season. Altogether, the study will provide a conception to the researchers in the fields mounting season-specific guidelines and mitigation approaches. Conclusively, the study commends future work focussing on defining the effects of other chemical components on particles and associated transition metal composition along with proper extenuation of the same.

A revision of the multiple-path particle dosimetry model focusing on tobacco product aerosol dynamics.

To assess the health impact of inhaled aerosols, it is necessary to understand aerosol dynamics and the associated dosimetry in the human respiratory tract. Although several studies have measured or simulated the dosimetry of aerosol constituents, the respiratory tract focus areas have been limited. In particular, the aerosols generated from tobacco products are complex composites and simulating their dynamics in the respiratory tract is challenging. To assess the dosimetry of the aerosol constituents of tobacco products, we developed a revised version of the Multiple-Path Particle Dosimetry (MPPD) model, which employs (1) new geometry based on CT-scanned human respiratory tract data, (2) convective mixing in the oral cavity and deep lung, and (3) constituent partitioning between the tissue and air, and clearance. The sensitivity analysis was conducted using aerosols composed of four major constituents of electronic cigarette (EC) aerosols to investigate the parameters that have a significant impact on the results. In addition, the revised model was run with 4 and 10 constituents in ECs and conventional cigarettes (CCs), respectively. Sensitivity analysis revealed that the new modeling and the physicochemical properties of constituents had a considerable impact on the simulated aerosol concentration and dosimetry. The simulations could be carried out within 3 min even when 10 constituents of CC aerosols were analyzed simultaneously. The revised model based on MPPD is an efficient and easy-to-use tool for understanding the aerosol dynamics of CC and EC constituents and their effect on the human body.

An integrated new approach methodology for inhalation risk assessment of safe and sustainable by design nanomaterials

The production and use of nanomaterials (NMs) has increased over the last decades posing relevant questions on their risk after release and exposure of the population or sub-populations. In this context, the safe and sustainable by design (SSbD) approach framework requires to assess the potential hazard connected with intrinsic properties of the material along the whole life cycle of the NM and/or of the nano enabled products. Moreover, in the last years, the use of new advanced methodologies (NAMs) has increasingly gained attention for the use of alternative methods in obtaining relevant information on NMs hazard and risk. Considering the SSbD and the NAMs frameworks, within the ASINA H2020 project, we developed new NAMs devoted at improving the hazard and risk definition of different Ag and TiO2 NPs. The NAMs are developed considering two air liquid interface exposure systems, the Vitrocell Cloud-α and the Cultex Compact module and the relevant steps to obtain reproducible exposures are described. The new NAMs build on the integration of environmental monitoring campaigns at nano-coating production sites, allowing the quantification by the multiple-path particle dosimetry (MPPD) model of the expected lung deposited dose in occupational settings. Starting from this information, laboratory exposures to the aerosolized NPs are performed by using air liquid interface exposure equipment and human alveolar cells (epithelial cells and macrophages), replicating the doses of exposure estimated in workers by MPPD. Preliminary results on cell viability and inflammatory responses are reported. The proposed NAMs may represent possible future reference procedures for assessing the NPs inhalation toxicology, supporting risk assessment at real exposure doses.

3D printer emissions elicit filament-specific and dose-dependent metabolic and genotoxic effects in human airway epithelial cells.

Three-dimensional (3D) printers have become popular educational tools in secondary and post-secondary STEM curriculum; however, concerns have emerged regarding inhalation exposures and associated health risks. Current evidence suggests that filament materials and site conditions may cause differences in the chemical profiles and toxicological properties of 3D printer emissions; however, few studies have evaluated exposures directly in the classroom. In this study, we monitored and sampled particulate matter (PM) emitted from acrylonitrile-butadiene-styrene (ABS) and polylactic acid (PLA) filaments during a 3-hour 3D printing session in a high school classroom using aerosol monitoring instrumentation and collection media. To evaluate potential inhalation risks, Multiple Path Particle Dosimetry (MPPD) modeling was used to estimate inhaled doses and calculate in vitro concentrations based on the observed aerosol data and specific lung and breathing characteristics. Dynamic light scattering was used to evaluate the hydrodynamic diameter, zeta potential, and polydispersity index (PDI) of extracted PM emissions dispersed in cell culture media. Small airway epithelial cells (SAEC) were employed to determine cellular viability, genotoxic, inflammatory, and metabolic responses to each emission exposure using MTS, ELISA, and high-performance liquid chromatography-mass spectrometry (HPLC-MS), respectively. Aerosol monitoring data revealed that emissions from ABS and PLA filaments generated similar PM concentrations within the ultrafine and fine ranges. However, DLS analysis showed differences in the physicochemical properties of ABS and PLA PM, where the hydrodynamic diameter of PLA PM was greater than ABS PM, which may have influenced particle deposition rates and cellular outcomes. While exposure to both ABS and PLA PM reduced cell viability and induced MDM2, an indicator of genomic instability, PLA PM alone increased gamma-H2AX, a marker of double-stranded DNA breaks. ABS and PLA emissions also increased the release of pro-inflammatory cytokines, although this did not reach significance. Furthermore, metabolic profiling via high performance liquid chromatography-mass spectrometry (HPLC-MS) and subsequent pathway analysis revealed filament and dose dependent cellular metabolic alterations. Notably, our metabolomic analysis also revealed key metabolites and pathways implicated in PM-induced oxidative stress, DNA damage, and respiratory disease that were perturbed across both tested doses for a given filament. Taken together, these findings suggest that use of ABS and PLA filaments in 3D printers within school settings may potentially contribute to adverse respiratory responses especially in vulnerable populations.

Assessment of seasonal variability of PM, BC and UFP levels at a highway toll stations and their associated health risks

As a part of their occupation, workers at toll stations are exposed to traffic emissions during the working shift, which sometimes stretches to 12 h. To assess the exposure and subsequent health risk of these workers, a study was performed on a highway toll station in India. PM1, PM2.5, PM10, BC and UFP concentration were determined inside a toll collectors’ cabin and outside in a free-flowing traffic section (125 m from the toll cabin). The concentrations varied in the following range: PM1 (40.69–226.13 μg m−3), PM2.5 (49.71–247.36 μg m−3), PM10 (83.15–458.14 μg m−3) and BC (2.1–87.5 μg m−3) and UFP: 101–53705 pt cm−3. The mean concentration inside the cabin was 1.34 (PM1), 1.35 (PM2.5), 1.16 (PM10) and 2.91 (BC) times the concentration outside for the summer season. The corresponding levels in the winter season were 1.14 (PM1), 1.11 (PM2.5), 1.11 (PM10), 2.50 (BC) and 1.82 (UFP). In addition to the exhaust emission, the non-exhaust emissions such as resuspension of crustal particles, fly ash and bioaerosols were identified. Using the Multiple Path Particle Dosimetry model for two groups - adults (18–21 years) and adults (21+ years), it was estimated that the pulmonary deposition of in-cabin workers were 50% (PM2.5) −75% (PM1) higher than the workers outside the cabin. Particle mass deposition was found to be higher for adults (21+ years) than adults (18–21 years) for both the seasons. The study quantitatively assessed the health risk faced by the workers in terms of exposure concentration and deposition in respiratory tract. More such studies at different traffic mix and climate can provide better estimates of health risk of toll workers that can be used to devise appropriate strategies for control of it.

Refinement of the acute inhalation limit test for inert, nano-sized dusts by an in silico dosimetry-based evaluation: case study for the dissolution of a regulatory dilemma.

This case study aims to describe the dilemma faced when exposing rats to very high concentrations of fine, pulverulent materials for acute inhalation studies and to address the regulatory question of whether the effects seen here are relevant to humans and the subject of classification according to the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). Many powders match the definition of nanomaterials in the EU; therefore, information on acute inhalation testing of powders up to the GHS cutoff of 5mg/L is required. However, testing rats at such a high aerosol concentration can cause physical obstruction of the airways and even mortality by suffocation. Therefore, to evaluate whether the physical effects on airway obstruction in rats exposed to 5mg/L for 4hours and alternative exposures to 1 and 2mg/L are relevant for humans, an in silico evaluation of aerosol deposition was conducted using the multiple-path particle dosimetry (MPPD) model. For this evaluation, actual exposure conditions for an organic, nano-sized pigment which produced 100% lethality in rats at 5mg/L, but not at 1mg/L, were used to assess the potential for airway obstruction in rats and accordingly in humans. As an indicator of the potential for airway obstruction, the ratio of the diameter of the deposited, aggregated aerosol to airway diameter was calculated for each exposure condition. For rats exposed to 5mg/L for 4h, approximately 75% of tracheobronchial and 22% of pulmonary/alveolar airways were considered vulnerable to significant or complete obstruction (ratios >0.5). In humans, an equivalent exposure resulted in just over 96% of human tracheobronchial airways that received deposited mass to airway diameter ratios between 0.3 and 0.4 (nasal) or 0.4 and 0.5 (oral), with no airways with ratios >0.5. For the pulmonary/alveolar region, ∼88% of the airways following nasal or oral breathing were predicted to have deposited aerosol diameter to airway diameter ratios <0.1, with no airways with ratios >0.5. Thus, the in silico results obtained for rats are in line with the pathological findings of the animal test. The predicted results in humans, however, affirm the hypothesis of a rat-specific high dose effect which does not justify a classification according to GHS.

Predictability Augmentation by In-silico Study to In-vivo and In-vitro Results of Lung Doses of Airborne Fine and Ultrafine Particles Inhaled by Humans at Industrial Workplaces

This study correlates computational predictions with in vivo and in vitro experimental results of inhaled fine and ultrafine particulate matter (PM) transport, dissemination, and deposition in the human respiratory airways. Epidemiological studies suggest that workplace exposure to anthropogenic pollutant PMs is a risk factor for increased susceptibility to acute broncho-pulmonary illnesses. However, investigations on detailed human inhalation and PM transport processes are restrictive from time, cost, and ethical perspectives. Computational simulation based on the Multiple Path Particle Dosimetry (MPPD) model was employed to quantify the risks associated with workplace exposure of these PMs. Here, the physical, mechanical, and electrical properties of PMs of carbon black (CB) and ultrafine particles (UFPs) from wire-cut electrical discharge machining (WEDM), with mass median aerodynamic diameter (CMAD) in the range of 1 nm to 1000 nm, were used as input parameters of MPPD. Additionally, it mimicked occupational workers’ age, body mass index, and oronasal-combinational nose and mouth breathing exposure time. The deposition results were compared with several vivo and in vitro experimental data reported in the literature, and satisfactory agreements were found. For example, a total lung dose of CB-PMs of 100 nm is the highest (28%), while a 380 nm dose is the lowest (15%). Afterward, deposition increases with particle size, reaching 26% for 1000 nm. In the case of WEDM-UFPs, about 98% of all 1.0 nm inhaled particles remain in the lung. Subsequently, the deposition dose decreases with the particle size and reaches up to 28% for 100 nm particles. Approximately 51% of deposited WEDM-UFPs are of CMAD ≤ 5 nm. The images of lung geometry also observed the maximum deposited mass and mass flux rate in the head, tracheobronchial, and pulmonary airways.

Health risk assessment of workers' exposure to BTEX and PM during refueling in an urban fuel station.

The proximity of fuel stations to the roads and the activities inside the station can contribute to PM and VOCs and impose health risks on station workers. The study presents the exposure and health risk assessment of the fuel station personnel to total volatile organic compounds (TVOCs) and particulate matter (PM) during refueling operations. TVOCs and PM monitoring were carried out at a fuel station in Chennai, India, for 1 week in March 2021, covering both weekdays and weekends. The health risks were assessed using EPA's health impact assessment methodology. Exposure to TVOCs (3177.39 ± 5450.32 μg/m3) exceeded the EPA standard of 5 μg/m3, by more than 500 times, peaking during refueling operations. The average concentrations of PM10, PM2.5, and PM1 were 76.55 ± 23.08 μg/m3, 41.81 ± 9 μg/m3, and 30.38 ± 7.56 μg/m3, respectively. The concentrations were observed to be high during morning and evening hours due to the increased traffic on the adjacent road and inside the fuel station. The synergistic health risks linked with long-term exposure to high concentrations of BTEX and PM were also estimated. At the fuel station, a significant contribution to the SOA formation potential was shown by toluene, followed by m-xylene, p-xylene, o-xylene, ethylbenzene, and benzene. Furthermore, the deposition of airborne particles in the workers' respiratory tract was calculated using the Multiple Path Particle Dosimetry model while considering the daily average exposure duration of 12 h. The results showed that 59% of PM10 particles were deposited in the head region, whereas 11% and 10% of PM2.5 and PM1 particles were deposited in the pulmonary region. Hence, the health risk assessment indicated no non-cancer risk of exposure to PM (hazard quotient = 0.13) to station personnel exposed regularly for 1 year. However, prolonged exposure to VOCs for more than 1 year can result in both carcinogenic and non-carcinogenic risk (hazard quotient = 0.045 and cancer risk > 10-6) in workers.

An experimental study on lung deposition of inhaled 2 μm particles in relation to lung characteristics and deposition models

BackgroundThe understanding of inhaled particle respiratory tract deposition is a key link to understand the health effects of particles or the efficiency for medical drug delivery via the lung. However, there are few experimental data on particle respiratory tract deposition, and the existing data deviates considerably when comparing results for particles > 1 μm.MethodsWe designed an experimental set-up to measure deposition in the respiratory tract for particles > 1 μm, more specifically 2.3 μm, with careful consideration to minimise foreseen errors. We measured the deposition in seventeen healthy adults (21–68 years). The measurements were performed at tidal breathing, during three consecutive 5-minute periods while logging breathing patterns. Pulmonary function tests were performed, including the new airspace dimension assessment (AiDA) method measuring distal lung airspace radius (rAiDA). The lung characteristics and breathing variables were used in statistical models to investigate to what extent they can explain individual variations in measured deposited particle fraction. The measured particle deposition was compared to values predicted with whole lung models. Model calculations were made for each subject using measured variables as input (e.g., breathing pattern and functional residual capacity).ResultsThe measured fractional deposition for 2.3 μm particles was 0.60 ± 0.14, which is significantly higher than predicted by any of the models tested, ranging from 0.37 ± 0.08 to 0.53 ± 0.09. The multiple-path particle dosimetry (MPPD) model most closely predicted the measured deposition when using the new PNNL lung model. The individual variability in measured particle deposition was best explained by breathing pattern and distal airspace radius (rAiDA) at half inflation from AiDA. All models underestimated inter-subject variability even though the individual breathing pattern and functional residual capacity for each participant was used in the model.ConclusionsWhole lung models need to be tuned and improved to predict the respiratory tract particle deposition of micron-sized particles, and to capture individual variations – a variation that is known to be higher for aged and diseased lungs. Further, the results support the hypothesis that the AiDA method measures dimensions in the peripheral lung and that rAiDA, as measured by the AiDA, can be used to better understand the individual variation in the dose to healthy and diseased lungs.

Particle size matters: Discrepancies in the health risks posed by traditional cigarettes and e-cigarettes in mice and humans

Electronic cigarettes (ECs), considered a healthier alternative to traditional cigarettes (TCs), vaporize e-liquid, which may produce harmful by-products due to thermal decomposition and metal transfer. These by-products' deposition in the respiratory tract is largely determined by particle size distribution (PSD). We employ the Multiple-Path Particle Dosimetry (MPPD) model to assess particle deposition within the human and mouse respiratory tracts. Leveraging the known connection between TC smoke inhalation and atherosclerosis, we used human aortic endothelial cells (HAECs) and ApoE-/- mice to explore the potential effects of EC aerosol inhalation on atherosclerosis. Our findings reveal that TCs exhibit a highly variable PSD, with mean diameters of approximately 300 nm for mainstream (MS) smoke and 120 nm for side stream (SS) smoke. Conversely, ECs demonstrate a more stable PSD. Combined with MPPD, the deposition fraction in the human respiratory system and mice is mainly deposited in the pulmonary region and head airway. For the Apoe-/- mice exposure experiment, preliminary findings suggest a potential impact on atherosclerosis, although not statistically significant, likely due to the limited sample size and exposure duration. This study highlights the importance of considering PSD, exposure dosage, and species-specific differences in risk assessments of EC aerosols.

Deposition of secondary organic aerosol in human lung model: Effect of photochemically aged aerosol on human respiratory system

Ultrafine particles (UFP) of Secondary Organic Aerosol (SOA) penetrate deep into the human respiratory system and exert fatal effects on human health. However, there is little data on the potential deposited doses of UFP-generated SOA in the human respiratory tract. This study is to estimate the fraction of aerosol deposition using a multiple-path-particle-dosimetry (MPPD) model. For relevancy of real life, the model employed measured concentrations of toluene-derived fresh and aged SOA produced within serially connected smog chamber and PAM-OFR (Potential Aerosol Mass-Oxidation Flow Reactor) under atmospheric environmental conditions (NOx and relative humidity). The number concentrations and chemical composition of fresh and aged aerosols produced within the chambers were measured using Scanning Mobility Particle Sizer (SMPS) and High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS), while the morphology of individual particles was analyzed using Scanning Electron Microscopy (SEM). The number concentration of aged SOA-w/s was more than double compared to that of fresh SOA-w/s (maximum reached after 10 h) with its size less than 100 nm. The O:C ratio for aged SOA-w/s were 0.96 and 1.15 depending on RH (0.96 at 3% RH and 1.15 at 50% RH), and individual spherical particles containing water were present in agglomerates with its size of less than 1 µm. In all inhalable fresh and aged SOA produced in the two chambers, 5–22% of aerosol is deposited in the Head airways, 4–8% in the tracheobronchial, and 8–34% in the alveolar regions. The predominant deposition of the aged aerosol occurred in the alveoli (in the generation 20th lobe), and the deposition faction in the alveoli was 2–3 times higher in the children group than the adults group. This study presented a quantitative exposure assessment of SOA generated under a realistic simulation and suggested the possibility of evaluating long-term exposure to SOA and potential health effects by determining the potential inhalable aerosol doses and the fraction of deposition in the human respiratory system.

Incense smoke (IS) inhalation exposure system: Physicochemical characterization, IS particle deposition and clearance in human airway using MPPD model

Incense smoke (IS) is source of indoor air pollution and key risk for diverse human diseases. Less information is available regarding controlled IS rodent inhalation exposure system and IS particulate matter (PM) deposition in human airways. Study aimed to demonstrate stable ISPM physicochemical parameters of 10 incense products inside the customized whole body inhalation exposure chamber (without animal) connected to smoke generation unit via aerosol mixing device. IS analyzed for size segregated PM emission, ISPM in vitro aerodynamics (MMAD and GSD determination), fine and ultrafine particle's SEM, SEM-EDX and PAH analysis. Using real life exposure scenario by utilizing MMAD, GSD and PM concentration after Tier 1 exposure assessment as key input parameters, ISPM dosimetry in infant (3 months) and adult (21 years male and female) human airways was calculated using multiple-path particle dosimetry (MPPD 3.04) modeling. Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) ranged between 0.55 and 2.10 μm and 1.22 to 1.77 (polydisperse) respectively. PM1.0 and PM0.1 showed multiple morphology and presence of heavy and trace elements. PAH like acenaphthylene, anthracene, fluorene, naphthalene and phenanthrene were detected (0.84–143.17 μg/g). MPPD results showed higher ISPM deposition in pulmonary region and lowest in trachea bronchial region. ISPM deposition in tissue was higher in lower, peripheral lung as compared to upper and central lung tissue. Whole body inhalation exposure system showed stable IS atmosphere (physicochemical parameters) indicating the device suitability in future inhalation studies. MPPD ISPM deposition fraction and clearance data showed deep lung penetrating and retention behavior with higher risk in infant followed by female and then male. These modeled particle deposition and clearance data may be useful in risk assessment analysis of IS.

Oxidative potential and source apportionment of size-resolved particles from indoor environments: Dithiothreitol (DTT) consumption and ROS production

Oxidation potential (OP) is an emerging index to measure the toxicity of atmospheric particulate matter (PM), but little research data on indoor PM OP are available. This study focuses on the size-resolved particle OP and source apportionment of PM from indoor environments. Different-size PM samples were gathered from March 6, 2022, to April 18, 2022, from offices, canteens, dormitories, and laboratories using Anderson samplers. Particles from these indoor environments were separated into nine size fractions, and the chemical components (including transition metals, ions, and water-soluble organic carbon (WSOC)) were measured. The water-soluble OP (OPws) of the investigated PM was highest in the dormitory (61.02 nmol min−1 μg−1) and lowest in the canteen (25.58 nmol min−1 μg−1), varying by factors of up to 2.38. Additionally, the particulate Mn (r2 = 0.94), Fe (r2 = 0.93), and Zn (r2 = 0.92) concentrations were closely related to OPws. The OPws distribution in indoor PM samples featured a single peak from 0.7 to 3.2 μm. ROS (·OH) showed the same trend (1.1–3.2 μm) as PM OP, which shows that PM3.2 is the main contributor to adverse health effects among all size fractions of PM due to the strengthened oxidative ability of PM3.2 compared to PM > 3.2. The source apportionment results showed that secondary sources (52.3%), construction sources (28%), vehicle emissions (18.5%), and dust sources (1.2%) were the main sources of indoor PM OP. Multiple path particle dosimetry (MPPD) model tests evidenced that PM3.2 control the lung OPws and ROS (accounting for >71.49% and 68.07%, respectively) deposition because of the high deposition efficiency and metal concentration in the alveolar region. The experimental trend of OP was closely related to that of ROS. Overall, since OPws is directly associated with diverse health effects for PM OP, special attention to PM3.2 impact.