Particulate matter constituents trigger the formation of extracellular amyloid ß and Tau -containing plaques and neurite shortening in vitro.

Air pollution is an environmental factor associated with an increased risk of neurodegenerative diseases, such as Alzheimer's and Parkinson's, characterized by decreased cognitive abilities and memory. The limited models of sporadic Alzheimer's disease fail to replicate all pathological hallmarks of the disease, making it challenging to uncover potential environmental causes. Environmentally driven models of Alzheimer's disease are thus timely and necessary. We used live-cell confocal fluorescent imaging combined with high-resolution stimulated emission depletion (STED) microscopy to follow the response of retinoic acid-differentiated human neuroblastoma SH-SY5Y cells to nanomaterial exposure. Here, we report that exposure of the cells to some particulate matter constituents reproduces a neurodegenerative phenotype, including extracellular amyloid beta-containing plaques and decreased neurite length. Consistent with the existing in vivo research, we observed detrimental effects, specifically a substantial reduction in neurite length and formation of amyloid beta plaques, after exposure to iron oxide and diesel exhaust particles. Conversely, after exposure to engineered cerium oxide nanoparticles, the lengths of neurites were maintained, and almost no extracellular amyloid beta plaques were formed. Although the exact mechanism behind this effect remains to be explained, the retinoic acid differentiated SH-SY5Y cell in vitro model could serve as an alternative, environmentally driven model of neurodegenerative diseases, including Alzheimer's disease.

Genotoxicity by rapeseed methyl ester and hydrogenated vegetable oil combustion exhaust products in lung epithelial (A549) cells.

Biofuel is an attractive substitute for petrodiesel because of its lower environmental footprint. For instance, the polycyclic aromatic hydrocarbons (PAH) emission per fuel energy content is lower for rapeseed methyl ester (RME) than for petrodiesel. This study assesses genotoxicity by extractable organic matter (EOM) of exhaust particles from the combustion of petrodiesel, RME, and hydrogenated vegetable oil (HVO) in lung epithelial (A549) cells. Genotoxicity was assessed as DNA strand breaks by the alkaline comet assay. EOM from the combustion of petrodiesel and RME generated the same level of DNA strand breaks based on the equal concentration of total PAH (i.e. net increases of 0.13 [95% confidence interval (CI): 0.002, 0.25, and 0.12 [95% CI: 0.01, 0.24] lesions per million base pairs, respectively). In comparison, the positive control (etoposide) generated a much higher level of DNA strand breaks (i.e. 0.84, 95% CI: 0.72, 0.97) lesions per million base pairs. Relatively low concentrations of EOM from RME and HVO combustion particles (<116 ng/ml total PAH) did not cause DNA strand breaks in A549 cells, whereas benzo[a]pyrene and PAH-rich EOM from petrodiesel combusted using low oxygen inlet concentration were genotoxic. The genotoxicity was attributed to high molecular weight PAH isomers with 5-6 rings. In summary, the results show that EOM from the combustion of petrodiesel and RME generate the same level of DNA strand breaks on an equal total PAH basis. However, the genotoxic hazard of engine exhaust from on-road vehicles is lower for RME than petrodiesel because of lower PAH emission per fuel energy content.

Indoor PM2.5 from occupied residences in Sweden caused higher inflammation in mice compared to outdoor PM2.5.

We spend most of our time indoors; however, little is known about the effects of exposure to aerosol particles indoors. We aimed to determine differences in relative toxicity and physicochemical properties of PM2.5 collected simultaneously indoors (PM2.5 INDOOR ) and outdoors (PM2.5 OUTDOOR ) in 15 occupied homes in southern Sweden. Collected particles were extracted from filters, pooled (indoor and outdoor separately), and characterized for chemical composition and endotoxins before being tested for toxicity in mice via intratracheal instillation. Various endpoints including lung inflammation, genotoxicity, and acute-phase response in lung and liver were assessed 1, 3, and 28 days post-exposure. Chemical composition of particles used in toxicological assessment was compared to particles analyzed without extraction. Time-resolved particle mass and number concentrations were monitored. PM2.5 INDOOR showed higher relative concentrations (µg mg-1 ) of metals, PAHs, and endotoxins compared to PM2.5 OUTDOOR . These differences may be linked to PM2.5 INDOOR causing significantly higher lung inflammation and lung acute-phase response 1 day post-exposure compared to PM2.5 OUTDOOR and vehicle controls, respectively. None of the tested materials caused genotoxicity. PM2.5 INDOOR displayed higher relative toxicity than PM2.5 OUTDOOR under the studied conditions, that is, wintertime with reduced air exchange rates, high influence of indoor sources, and relatively low outdoor concentrations of PM. Reducing PM2.5 INDOOR exposure requires reduction of both infiltration from outdoors and indoor-generated particles.

A controlled chamber study of effects of exposure to diesel exhaust particles and noise on heart rate variability and endothelial function.

BACKGROUND: Adverse cardiovascular effects are associated with both diesel exhaust and road traffic noise, but these exposures are hard to disentangle epidemiologically. We used an experimental setup to evaluate the impact of diesel exhaust particles and traffic noise, alone and combined, on intermediary outcomes related to the autonomic nervous system and increased cardiovascular risk. METHODS: In a controlled chamber 18 healthy adults were exposed to four scenarios in a randomized cross-over fashion. Each exposure scenario consisted of either filtered (clean) air or diesel engine exhaust (particle mass concentrations around 300 µg/m3), and either low (46 dB(A)) or high (75 dB(A)) levels of traffic noise for 3 h at rest. ECG was recorded for 10-min periods before and during each exposure type, and frequency-domain heart rate variability (HRV) computed. Endothelial dysfunction and arterial stiffness were assessed after each exposure using EndoPAT 2000. RESULTS: Compared to control exposure, HRV in the high frequency band decreased during exposure to diesel exhaust, both alone and combined with noise, but not during noise exposure only. These differences were more pronounced in women. We observed no synergistic effects of combined exposure, and no significant differences between exposure scenarios for other HRV indices, endothelial function or arterial stiffness. CONCLUSION: Three-hour exposure to diesel exhaust, but not noise, was associated with decreased HRV in the high frequency band. This indicates activation of irritant receptor-mediated autonomic reflexes, a possible mechanism for the cardiovascular risks of diesel exposure. There was no effect on endothelial dysfunction or arterial stiffness after exposure.

Real-Time Emission and Exposure Measurements of Multi-walled Carbon Nanotubes during Production, Power Sawing, and Testing of Epoxy-Based Nanocomposites.

OBJECTIVES: The use of manufactured nanomaterials is increasing globally. Although multi-walled carbon nanotubes (CNTs) are used in a wide range of applications, only limited data are available on emissions and exposures during CNT composite production. No exposure data using portable aethalometers in the personal breathing zone (PBZ) to monitor occupational exposure to CNTs have yet been published. The aim of this study was to characterize emissions of and exposures to CNTs during CNT composite production, sawing, and shear testing. We also investigated whether real-time aethalometer measurements of equivalent black carbon (eBC) could be used as a proxy filter sampling of elemental carbon (EC). The presence of CNTs as surface contamination in the production facility was monitored since this could contribute to airborne exposure. METHODS: During CNT composite production in an industrial setting including both chemical and manufacturing laboratories, different work tasks (WTs) were studied with a combination of direct-reading instruments (aethalometer, aerodynamic particle sizer, condensation particle counter) and filter-based methods. Measurements were performed to monitor concentrations in the emission zone (EZ), PBZ, and background zone. The filter samples were analysed for EC and fibre concentration of CNTs using scanning electron microscopy (SEM). Additionally, surfaces in the facility were tape sampled for monitoring of CNT contamination, and analysed with SEM. RESULTS: Clear eBC peaks were observed in the PBZ during several WTs, most clearly during open handling of CNT powder. Power sawing emitted the highest particle number concentration in the EZ of both nanoparticles and coarse particles, but no individual airborne CNTs, agglomerates, or aggregates were detected. Airborne CNTs were identified, for example, in a filter sample collected in the PBZ of a worker during mixing of CNT epoxy. The airborne CNT particles were large agglomerates which looked like porous balls in the SEM images. Significant EC exposures were found in the inhalable fraction while all respirable fractions of EC were below detection. The highest inhalable EC concentrations were detected during the composite production. No significant correlation was found between inhalable EC and eBC, most likely due to losses of large EC containing particles in the sampling lines and inside the eBC monitor. In total, 39 tape samples were collected. Surface contamination of CNTs was detected on eight surfaces in the chemical and manufacturing laboratories, mainly in the near-field zone. Elongated CNT-like features were detected in the sawdust after sawing of CNT composite. CONCLUSIONS: Characterization of a workplace producing CNT composite showed that open handling of the CNT powder during weighing and mixing of CNT powder material generated the highest particle emissions and exposures. The portable direct-reading aethalometer provided time-resolved eBC exposure data with complementary information to time-integrated EC filter samples by linking peak exposures to specific WTs. Based on the results it was not possible to conclude that eBC is a good proxy of EC. Surface contamination of CNTs was detected on several surfaces in the near-field zone in the facility. This contamination could potentially be resuspended into the workplace air, and may cause secondary inhalation exposure.

Underground emissions and miners' personal exposure to diesel and renewable diesel exhaust in a Swedish iron ore mine.

PURPOSE: Underground diesel exhaust exposure is an occupational health risk. It is not known how recent intensified emission legislation and use of renewable fuels have reduced or altered occupational exposures. We characterized these effects on multipollutant personal exposure to diesel exhaust and underground ambient air concentrations in an underground iron ore mine. METHODS: Full-shift personal sampling (12 workers) of elemental carbon (EC), nitrogen dioxide (NO2), polycyclic aromatic hydrocarbons (PAHs), and equivalent black carbon (eBC) was performed. The study used and validated eBC as an online proxy for occupational exposure to EC. Ambient air sampling of these pollutants and particle number size distribution and concentration were performed in the vicinity of the workers. Urine samples (27 workers) were collected after 8 h exposure and analyzed for PAH metabolites and effect biomarkers (8-oxodG for DNA oxidative damage, 4-HNE-MA for lipid peroxidation, 3-HPMA for acrolein). RESULTS: The personal exposures (geometric mean; GM) of the participating miners were 7 µg EC m-3 and 153 µg NO2 m-3, which are below the EU occupational exposure limits. However, exposures up to 94 µg EC m-3 and 1200 µg NO2 m-3 were observed. There was a tendency that the operators of vehicles complying with sharpened emission legislation had lower exposure of EC. eBC and NO2 correlated with EC, R = 0.94 and R = 0.66, respectively. No correlation was found between EC and the sum of 16 priority PAHs (GM 1790 ng m-3). Ratios between personal exposures and ambient concentrations were similar and close to 1 for EC and NO2, but significantly higher for PAHs. Semi-volatile PAHs may not be effectively reduced by the aftertreatment systems, and ambient area sampling did not predict the personal airborne PAHs exposure well, neither did the slightly elevated concentration of urinary PAH metabolites correlate with airborne PAH exposure. CONCLUSION: Miners' exposures to EC and NO2 were lower than those in older studies indicating the effect of sharpened emission legislation and new technologies. Using modern vehicles with diesel particulate filter (DPF) may have contributed to the lower ambient underground PM concentration and exposures. The semi-volatile behavior of the PAHs might have led to inefficient removal in the engines aftertreatment systems and delayed removal by the workplace ventilation system due to partitioning to indoor surfaces. The results indicate that secondary emissions can be an important source of gaseous PAH exposure in the mine.

Lung function and self-rated symptoms in healthy volunteers after exposure to hydrotreated vegetable oil (HVO) exhaust with and without particles.

BACKGROUND: Diesel engine exhaust causes adverse health effects. Meanwhile, the impact of renewable diesel exhaust, such as hydrotreated vegetable oil (HVO), on human health is less known. Nineteen healthy volunteers were exposed to HVO exhaust for 3 h in a chamber with a double-blind, randomized setup. Exposure scenarios comprised of HVO exhaust from two modern non-road vehicles with 1) no aftertreatment system ('HVOPM+NOx' PM1: 93 µg m-3, EC: 54 µg m-3, NO: 3.4 ppm, NO2: 0.6 ppm), 2) an aftertreatment system containing a diesel oxidation catalyst and a diesel particulate filter ('HVONOx' PM1: ~ 1 µg m-3, NO: 2.0 ppm, NO2: 0.7 ppm) and 3) filtered air (FA) as control. The exposure concentrations were in line with current EU occupational exposure limits (OELs) of NO, NO2, formaldehyde, polycyclic aromatic hydrocarbons (PAHs), and the future OEL (2023) of elemental carbon (EC). The effect on nasal patency, pulmonary function, and self-rated symptoms were assessed. Calculated predicted lung deposition of HVO exhaust particles was compared to data from an earlier diesel exhaust study. RESULTS: The average total respiratory tract deposition of PM1 during HVOPM+NOx was 27 µg h-1. The estimated deposition fraction of HVO PM1 was 40-50% higher compared to diesel exhaust PM1 from an older vehicle (earlier study), due to smaller particle sizes of the HVOPM+NOx exhaust. Compared to FA, exposure to HVOPM+NOx and HVONOx caused higher incidence of self-reported symptoms (78%, 63%, respectively, vs. 28% for FA, p < 0.03). Especially, exposure to HVOPM+NOx showed 40-50% higher eye and throat irritation symptoms. Compared to FA, a decrement in nasal patency was found for the HVONOx exposures (- 18.1, 95% CI: - 27.3 to - 8.8 L min-1, p < 0.001), and for the HVOPM+NOx (- 7.4 (- 15.6 to 0.8) L min-1, p = 0.08). Overall, no clinically significant change was indicated in the pulmonary function tests (spirometry, peak expiratory flow, forced oscillation technique). CONCLUSION: Short-term exposure to HVO exhaust concentrations corresponding to EU OELs for one workday did not cause adverse pulmonary function changes in healthy subjects. However, an increase in self-rated mild irritation symptoms, and mild decrease in nasal patency after both HVO exposures, may indicate irritative effects from exposure to HVO exhaust from modern non-road vehicles, with and without aftertreatment systems.

Biomarkers after Controlled Inhalation Exposure to Exhaust from Hydrogenated Vegetable Oil (HVO).

Hydrogenated vegetable oil (HVO) is a renewable diesel fuel used to replace petroleum diesel. The organic compounds in HVO are poorly characterized; therefore, toxicological properties could be different from petroleum diesel exhaust. The aim of this study was to evaluate the exposure and effective biomarkers in 18 individuals after short-term (3 h) exposure to HVO exhaust and petroleum diesel exhaust fumes. Liquid chromatography tandem mass spectrometry was used to analyze urinary biomarkers. A proximity extension assay was used for the measurement of inflammatory proteins in plasma samples. Short-term (3 h) exposure to HVO exhaust (PM1 ~1 µg/m3 and ~90 µg/m3 for vehicles with and without exhaust aftertreatment systems, respectively) did not increase any exposure biomarker, whereas petroleum diesel exhaust (PM1 ~300 µg/m3) increased urinary 4-MHA, a biomarker for p-xylene. HVO exhaust from the vehicle without exhaust aftertreatment system increased urinary 4-HNE-MA, a biomarker for lipid peroxidation, from 64 ng/mL urine (before exposure) to 141 ng/mL (24 h after exposure, p < 0.001). There was no differential expression of plasma inflammatory proteins between the HVO exhaust and control exposure group. In conclusion, short-term exposure to low concentrations of HVO exhaust did not increase urinary exposure biomarkers, but caused a slight increase in lipid peroxidation associated with the particle fraction.

Emissions of soot, PAHs, ultrafine particles, NOx, and other health relevant compounds from stressed burning of candles in indoor air.

Burning candles release a variety of pollutants to indoor air, some of which are of concern for human health. We studied emissions of particles and gases from the stressed burning of five types of pillar candles with different wax and wick compositions. The stressed burning was introduced by controlled fluctuating air velocities in a 21.6 m3 laboratory chamber. The aerosol physicochemical properties were measured both in well-mixed chamber air and directly above the candle flame with online and offline techniques. All candles showed different emission profiles over time with high repeatability among replicates. The particle mass emissions from stressed burning for all candle types were dominated by soot (black carbon; BC). The wax and wick composition strongly influenced emissions of BC, PM2.5 , and particle-phase polycyclic aromatic hydrocarbons (PAHs), and to lower degree ultrafine particles, inorganic and organic carbon fraction of PM, but did not influence NOx , formaldehyde, and gas-phase PAHs. Measurements directly above the flame showed empirical evidence of short-lived strong emission peaks of soot particles. The results show the importance of including the entire burn time of candles in exposure assessments, as their emissions can vary strongly over time. Preventing stressed burning of candles can reduce exposure to pollutants in indoor air.

Emissions of ultrafine particles from five types of candles during steady burn conditions.

Emissions from candles are of concern for indoor air quality. In this work, five different types of pillar candles were burned under steady burn conditions in a new laboratory scale system for repeatable and controlled comparison of candle emissions (temperature ~25°C, relative humidity ~13%, O2 >18%, air exchange rate 1.9 h-1 ). Burn rate, particle number concentrations, mass concentrations, and mode diameters varied between candle types. Based on the results, the burning period was divided in two phases: initial (0-1 h) and stable (1-6 h). Burn rates were in the range 4.4-7.3 and 4.7-7.1 g/h during initial and stable phase, respectively. Relative particle number emissions, mode diameters, and mass concentrations were higher during the initial phase compared to the stable phase for a majority of the candles. We hypothesize that this is due to elevated emissions of wick additives upon ignition of the candle together with a slightly higher burn rate in the initial phase. Experiments at higher relative humidity (~40%) gave similar results with a tendency toward larger particle sizes at the higher relative humidity. Chemical composition with respect to inorganic salts was similar in the emitted particles (dry conditions) compared to the candlewicks, but with variations between different candles.

Emissions and exposures of graphene nanomaterials, titanium dioxide nanofibers, and nanoparticles during down-stream industrial handling.

Today, engineered nanomaterials are frequently used. Nanosized titanium dioxide (TiO2) has been extensively used for many years and graphene is one type of emerging nanomaterial. Occupational airborne exposures to engineered nanomaterials are important to ensure safe workplaces and to extend the information needed for complete risk assessments. The main aim of this study was to characterize workplace emissions and exposure of graphene nanoplatelets, graphene oxide, TiO2 nanofibers (NFs) and nanoparticles (NPs) during down-stream industrial handling. Surface contaminations were also investigated to assess the potential for secondary inhalation exposures. In addition, a range of different sampling and aerosol monitoring methods were used and evaluated. The results showed that powder handling, regardless of handling graphene nanoplatelets, graphene oxide, TiO2 NFs, or NPs, contributes to the highest particle emissions and exposures. However, the exposure levels were below suggested occupational exposure limits. It was also shown that a range of different methods can be used to selectively detect and quantify nanomaterials both in the air and as surface contaminations. However, to be able to make an accurate determination of which nanomaterial that has been emitted a combination of different methods, both offline and online, must be used.

Particle characterization and toxicity in C57BL/6 mice following instillation of five different diesel exhaust particles designed to differ in physicochemical properties.

BACKGROUND: Diesel exhaust is carcinogenic and exposure to diesel particles cause health effects. We investigated the toxicity of diesel exhaust particles designed to have varying physicochemical properties in order to attribute health effects to specific particle characteristics. Particles from three fuel types were compared at 13% engine intake O2 concentration: MK1 ultra low sulfur diesel (DEP13) and the two renewable diesel fuels hydrotreated vegetable oil (HVO13) and rapeseed methyl ester (RME13). Additionally, diesel particles from MK1 ultra low sulfur diesel were generated at 9.7% (DEP9.7) and 17% (DEP17) intake O2 concentration. We evaluated physicochemical properties and histopathological, inflammatory and genotoxic responses on day 1, 28, and 90 after single intratracheal instillation in mice compared to reference diesel particles and carbon black. RESULTS: Moderate variations were seen in physical properties for the five particles: primary particle diameter: 15-22 nm, specific surface area: 152-222 m2/g, and count median mobility diameter: 55-103 nm. Larger differences were found in chemical composition: organic carbon/total carbon ratio (0.12-0.60), polycyclic aromatic hydrocarbon content (1-27 µg/mg) and acid-extractable metal content (0.9-16 µg/mg). Intratracheal exposure to all five particles induced similar toxicological responses, with different potency. Lung particle retention was observed in DEP13 and HVO13 exposed mice on day 28 post-exposure, with less retention for the other fuel types. RME exposure induced limited response whereas the remaining particles induced dose-dependent inflammation and acute phase response on day 1. DEP13 induced acute phase response on day 28 and inflammation on day 90. DNA strand break levels were not increased as compared to vehicle, but were increased in lung and liver compared to blank filter extraction control. Neutrophil influx on day 1 correlated best with estimated deposited surface area, but also with elemental carbon, organic carbon and PAHs. DNA strand break levels in lung on day 28 and in liver on day 90 correlated with acellular particle-induced ROS. CONCLUSIONS: We studied diesel exhaust particles designed to differ in physicochemical properties. Our study highlights specific surface area, elemental carbon content, PAHs and ROS-generating potential as physicochemical predictors of diesel particle toxicity.

Cooking and electronic cigarettes leading to large differences between indoor and outdoor particle composition and concentration measured by aerosol mass spectrometry.

We spend about two thirds of our time in private homes where airborne particles of indoor and outdoor origins are present. The negative health effects of exposure to outdoor particles are known. The characteristics of indoor airborne particles, though, are not well understood. This study assesses the differences in chemical composition of PM1 (<1 µm) inside and outside of an occupied Swedish residence in real time with a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and an Aethalometer. The chemical composition and concentration of particles indoors showed large differences compared to outdoors. The average indoor concentration was 15 µg m-3 and was higher than the outdoor 7 µg m-3. Organics dominated indoor particle composition (86% of the total mass) and originated from indoor sources (cooking, e-cigarette vaping). The average indoor to outdoor ratios were 5.5 for organic matter, 1.0 for black carbon, 0.6 for sulphate, 0.1 for nitrate, 0.2 for ammonium and 0.2 for chloride. The occupancy time accounted for 97% of the total measured period. Four factors were identified in the source apportionment of organic particle fraction by applying positive matrix factorization (PMF): two cooking factors, one e-cigarette factor and one outdoor contribution (OOA) organic factor penetrated from outside.

Workplace Emissions and Exposures During Semiconductor Nanowire Production, Post-production, and Maintenance Work.

BACKGROUND: Nanowires are a high-aspect-ratio material of increasing interest for a wide range of applications. A new and promising method to produce nanowires is by aerotaxy, where the wires are grown in a continuous stream of gas. The aerotaxy method can grow nanowires much faster than by more conventional methods. Nanowires have important properties in common with asbestos fibers, which indicate that there can be potential health effects if exposure occurs. No conclusive exposure (or emission) data from aerotaxy-production of nanowires has so far been published. METHODS: Different work tasks during semiconductor nanowire production, post-production, and maintenance were studied. A combination of direct-reading instruments for number concentration (0.007-20 µm) and filter sampling was used to assess the emissions (a couple of centimeter from the emission sources), the exposure in the personal breathing zone (max 30 cm from nose-mouth), and the concentrations in the background zone (at least 3 m from any emission source). The filters were analyzed for metal dust composition and number concentration of nanowires. Various surfaces were sampled for nanowire contamination. RESULTS: The particle concentrations in the emission zone (measured with direct-reading instruments) were elevated during cleaning of arc discharge, manual reactor cleaning, exchange of nanowire outflow filters, and sonication of substrates with nanowires. In the case of cleaning of the arc discharge and manual reactor cleaning, the emissions affected the concentrations in the personal breathing zone and were high enough to also affect the concentrations in the background. Filter analysis with electron microscopy could confirm the presence of nanowires in some of the air samples. CONCLUSIONS: Our results show that a major part of the potential for exposure occurs not during the actual manufacturing, but during the cleaning and maintenance procedures. The exposures and emissions were evaluated pre- and post-upscaling the production and showed that some work tasks (e.g. exchange of nanowire outflow filters and sonication of substrates with nanowires) increased the emissions post-upscaling.

Influence of Airborne Particles' Chemical Composition on SVOC Uptake from PVC Flooring-Time-Resolved Analysis with Aerosol Mass Spectrometry.

We sampled ammonium sulfate particles and indoor particles of outdoor origin through a small chamber covered with polyvinyl chloride flooring. We measured the uptake of semivolatile organic compounds (SVOCs) by the airborne particles in real time. The particles acquired SVOC mass fractions up to 10%. The phthalate ester (di(2-ethylhexyl)phthalate) (DEHP), a known endocrine disruptor, contributed by approximately half of the sorbed SVOC mass. The indoor particles acquired a higher DEHP fraction than laboratory-generated ammonium sulfate aerosol. We attribute this increased uptake to absorption by organic matter present in the indoor particles. Using a thermodenuder to remove volatile components, predominantly organics, reduced the SVOC uptake. Positive matrix factorization applied to the organic mass spectra suggests that hydrocarbon-like organic aerosol (typically fresh traffic exhaust) sorbs DEHP more efficiently than aged organic aerosol. The SVOC uptake is one of the processes that modify outdoor pollution particles after they penetrate buildings, where the majority of exposure occurs. Particles from indoor sources, typically dominated by organic matter, will undergo such processes as well. Aerosol mass spectrometry improves the time resolution of experimental investigations into these processes and enables experiments with lower, relevant particle concentrations. Additionally, particle size-resolved results are readily obtained.

Excretion of Urinary Metabolites of the Phthalate Esters DEP and DEHP in 16 Volunteers after Inhalation and Dermal Exposure.

Phthalate esters are suspected endocrine disruptors that are found in a wide range of applications. The aim of this study was to determine the excretion of urinary metabolites in 16 individuals after inhalation and/or dermal exposure to 100⁻300 µg/m³ of deuterium-labelled diethyl phthalate (D4-DEP) and bis(2-ethylhexyl) phthalate (D4-DEHP). Dermal exposure in this study represents a case with clean clothing acting as a barrier. After inhalation, D4-DEP and D4-DEHP metabolites were excreted rapidly, though inter-individual variation was high. D4-DEP excretion peaked 3.3 h (T½ of 2.1 h) after combined inhalation and dermal exposure, with total excreted metabolite levels ranging from 0.055 to 2.351 nmol/nmol/m³ (nmol of urinary metabolites per phthalates air concentration in (nmol/m³)). After dermal exposure to D4-DEP, metabolite excretion peaked 4.6 h (T½ of 2.7 h) after exposure, with excreted metabolite levels in between 0.017 and 0.223 nmol/nmol/m³. After combined inhalation and dermal exposure to D4-DEHP, the excretion of all five analysed metabolites peaked after 4.7 h on average (T½ of 4.8 h), and metabolite levels ranged from 0.072 to 1.105 nmol/nmol/m³ between participants. No dermal uptake of particle phase D4-DEHP was observed. In conclusion, the average excreted levels of metabolites after combined inhalation and dermal exposure to D4-DEP was three times higher than after combined exposure to D4-DEHP; and nine times higher than after dermal exposure of D4-DEP. This study was made possible due to the use of novel approaches, i.e., the use of labelled phthalate esters to avoid the background concentration, and innovative technique of phthalate generation, both in the particle and the gas phase.

Inhalation and Dermal Uptake of Particle and Gas-Phase Phthalates-A Human Exposure Study.

Phthalates are ubiquitous in indoor environments, which raises concern about their endocrine-disrupting properties. However, studies of human uptake from airborne exposure are limited. We studied the inhalation uptake and dermal uptake by air-to-skin transfer with clean clothing as a barrier of two deuterium-labeled airborne phthalates: particle-phase D4-DEHP (di(2-ethylhexyl)phthalate) and gas-phase D4-DEP (diethyl phthalate). Sixteen participants, wearing trousers and long-sleeved shirts, were under controlled conditions exposed to airborne phthalates in four exposure scenarios: dermal uptake alone and combined inhalation + dermal uptake of both phthalates. The results showed an average uptake of D4-DEHP by inhalation of 0.0014 ± 0.00088 (µg kg-1 bw)/(µg m-3)/h. No dermal uptake of D4-DEHP was observed during the 3 h exposure with clean clothing. The deposited dose of D4-DEHP accounted for 26% of the total inhaled D4-DEHP mass. For D4-DEP, the average uptake by inhalation + dermal was 0.0067 ± 0.0045 and 0.00073 ± 0.00051 (µg kg-1 bw)/(µg m-3)/h for dermal uptake. Urinary excretion factors of metabolites after inhalation were estimated to 0.69 for D4-DEHP and 0.50 for D4-DEP. Under the described settings, the main uptake of both phthalates was through inhalation. The results demonstrate the differences in uptake of gas and particles and highlight the importance of considering the deposited dose in particle uptake studies.

Comprehensive proteome analysis of nasal lavage samples after controlled exposure to welding nanoparticles shows an induced acute phase and a nuclear receptor, LXR/RXR, activation that influence the status of the extracellular matrix.

BACKGROUND: Epidemiological studies have shown that many welders experience respiratory symptoms. During the welding process a large number of airborne nanosized particles are generated, which might be inhaled and deposited in the respiratory tract. Knowledge of the underlying mechanisms behind observed symptoms is still partly lacking, although inflammation is suggested to play a central role. The aim of this study was to investigate the effects of welding fume particle exposure on the proteome expression level in welders suffering from respiratory symptoms, and changes in protein mediators in nasal lavage samples were analyzed. Such mediators will be helpful to clarify the pathomechanisms behind welding fume particle-induced effects. METHODS: In an exposure chamber, 11 welders with work-related symptoms in the lower airways during the last month were exposed to mild-steel welding fume particles (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Nasal lavage samples were collected before, immediately after, and the day after exposure. The proteins in the nasal lavage were analyzed with two different mass spectrometry approaches, label-free discovery shotgun LC-MS/MS and a targeted selected reaction monitoring LC-MS/MS analyzing 130 proteins and four in vivo peptide degradation products. RESULTS: The analysis revealed 30 significantly changed proteins that were associated with two main pathways; activation of acute phase response signaling and activation of LXR/RXR, which is a nuclear receptor family involved in lipid signaling. Connective tissue proteins and proteins controlling the degradation of such tissues, including two different matrix metalloprotease proteins, MMP8 and MMP9, were among the significantly changed enzymes and were identified as important key players in the pathways. CONCLUSION: Exposure to mild-steel welding fume particles causes measurable changes on the proteome level in nasal lavage matrix in exposed welders, although no clinical symptoms were manifested. The results suggested that the exposure causes an immediate effect on the proteome level involving acute phase proteins and mediators regulating lipid signaling. Proteases involved in maintaining the balance between the formation and degradation of extracellular matrix proteins are important key proteins in the induced effects.

Acute respiratory effects and biomarkers of inflammation due to welding-derived nanoparticle aggregates.

PURPOSE: Welders are exposed to airborne particles from the welding environment and often develop symptoms work-related from the airways. A large fraction of the particles from welding are in the nano-size range. In this study we investigate if the welders' airways are affected by exposure to particles derived from gas metal arc welding in mild steel in levels corresponding to a normal welding day. METHOD: In an exposure chamber, 11 welders with and 10 welders without work-related symptoms from the lower airways and 11 non-welders without symptoms, were exposed to welding fumes (1 mg/m3) and to filtered air, respectively, in a double-blind manner. Symptoms from eyes and upper and lower airways and lung function were registered. Blood and nasal lavage (NL) were sampled before, immediately after and the morning after exposure for analysis of markers of oxidative stress. Exhaled breath condensate (EBC) for analysis of leukotriene B4 (LT-B4) was sampled before, during and immediately after exposure. RESULTS: No adverse effects of welding exposure were found regarding symptoms and lung function. However, EBC LT-B4 decreased significantly in all participants after welding exposure compared to filtered air. NL IL-6 increased immediately after exposure in the two non-symptomatic groups and blood neutrophils tended to increase in the symptomatic welder group. The morning after, neutrophils and serum IL-8 had decreased in all three groups after welding exposure. Remarkably, the symptomatic welder group had a tenfold higher level of EBC LT-B4 compared to the two groups without symptoms. CONCLUSION: Despite no clinical adverse effects at welding, changes in inflammatory markers may indicate subclinical effects even at exposure below the present Swedish threshold limit (8 h TWA respirable dust).