Acute Inhalation Toxicity After Inhalation of ZnO Nanoparticles: Lung Surfactant Function Inhibition In Vitro Correlates With Reduced Tidal Volume in Mice.

People can be exposed to zinc oxide (ZnO) by inhalation of consumer products or during industrial processes. Zinc oxide nanoparticle (NP) exposure can induce acute inhalation toxicity. The toxicological mechanisms underlying the acute effects on the lungs have long focused on the phagolysosomal dissolution of ZnO NPs in macrophages followed by the release of free Zn2+ ions. However, we postulate an alternative mechanism based on the direct interaction of ZnO NPs with the lung surfactant (LS) layer covering the inside of the alveoli. Therefore, we tested the effect of ZnO NPs and Zn2+ ions on the function of LS in vitro using the constrained drop surfactometer. We found that the ZnO NPs inhibited the LS function, whereas Zn2+ ions did not. To examine the role of lung macrophages in the acute toxicity of inhaled ZnO NPs, mice were treated with Clodrosome, a drug that depletes alveolar macrophages, or Encapsome, the empty carrier of the drug. After macrophage depletion, the mice were exposed to an aerosol of ZnO NPs in whole body plethysmographs recording breathing patterns continuously. Mice in both groups developed shallow breathing (reduced tidal volume) shortly after the onset of exposure to ZnO NPs. This suggests a macrophage-independent mechanism of induction. This study shows that acute inhalation toxicity is caused by ZnO NP interaction with LS, independently of NP dissolution in macrophages.

Biocidal spray product exposure: Measured gas, particle, and surface concentrations compared with spray model simulations.

The purpose of the study was to compare measured air and surface concentrations after application of biocidal spray products with concentrations simulated with the ConsExpo Web spray simulation tool. Three different biocidal spray products were applied in a 20 m3 climate test chamber with well-controlled environmental conditions (22 ± 1 °C, 50 ± 2% relative humidity, and air exchange rate of 0.5 h-1). The products included an insect spray in a pressurized spray can, another insect spray product, and a disinfectant, the latter two applied separately with the same pumped spray device. The measurements included released particles, airborne organic compounds in both gas and particle phase, and surface concentrations of organic compounds on the wall and floor in front of the spraying position and on the most remote wall. Spraying time was a few seconds and the air concentrations were measured by sampling on adsorbent tubes at 9-13 times points during 4 hr after spraying. The full chamber experiment was repeated 2-3 times for each product. Due to sedimentation the concentrations of the particles in air decayed faster than explained by the air exchange rate. In spite of that, the non-volatile benzalkonium chlorides in the disinfectant could be measured in the air more than 30 min after spraying. ConsExpo Web simulated concentrations that were about half of the measured concentrations of the active substances when as many as possible of the default simulation parameters were replaced by the experimental values. ConsExpo Web was unable to simulate the observed faster decay of the airborne concentrations of the active substances, which might be due to underestimation of the gravitational particle deposition rates. There was a relatively good agreement between measured surface concentrations on the floor and calculated values based on the dislodgeable amount given in the selected ConsExpo Web scenarios. It is suggested to always supplement simulation tool results with practical measurements when assessing the exposure to a spray product.

Exposure to Air Pollution inside Electric and Diesel-Powered Passenger Trains.

Diesel-powered trains are used worldwide for passenger transport. The present study aimed to assess air pollution concentrations in passenger cars from diesel and electric trains. Personal exposure monitoring (6-7 h per day) was carried out for 49 days on diesel and 22 days on electric trains. Diesel trains had higher concentrations of all the assessed air pollution components. Average increases (and fold differences) in passenger cars of diesel trains compared with electric trains were for ultrafine particles 212 000 particles/cm3 (35-fold), black carbon 8.3 µg/m3 (6-fold), NO x 316 µg/m3 (8-fold), NO2 38 µg/m3 (3-fold), PM2.5 34 µg/m3 (2-fold), and benzo( a)pyrene 0.14 ng/m3 (6-fold). From time-series data, the pull and push movement modes, the engine in use, and the distance to the locomotive influenced the concentrations inside the diesel trains. In conclusion, concentrations of all air pollutants were significantly elevated in passenger cars in diesel trains compared to electric trains.

Effects of maternal inhalation of carbon black nanoparticles on reproductive and fertility parameters in a four-generation study of male mice.

BACKGROUND: Previous findings indicate that in utero exposure to nanoparticles may affect the reproductive system in male offspring. Effects such as decreased sperm counts and testicular structural changes in F1 males have been reported following maternal airway exposure to carbon black during gestation. In addition, a previous study in our laboratory suggested that the effects of in utero exposure of nanoparticles may span further than the first generation, as sperm content per gram of testis was significantly lowered in F2 males. In the present study we assessed male fertility parameters following in utero inhalation exposure to carbon black in four generations of mice. RESULTS: Filter measurements demonstrated that the time-mated females were exposed to a mean total suspended particle mass concentration of 4.79 ± 1.86 or 33.87 ± 14.77 mg/m3 for the low and high exposure, respectively. The control exposure was below the detection limit (LOD 0.08 mg/m3). Exposure did not affect gestation and litter parameters in any generation. No significant changes were observed in body and reproductive organ weights, epididymal sperm parameters, daily sperm production, plasma testosterone or fertility. CONCLUSION: In utero exposure to carbon black nanoparticles, at occupationally relevant exposure levels, via maternal whole body inhalation did not affect male-specific reproductive, fertility and litter parameters in four generations of mice.

Health effects of exposure to diesel exhaust in diesel-powered trains.

BACKGROUND: Short-term controlled exposure to diesel exhaust (DE) in chamber studies have shown mixed results on lung and systemic effects. There is a paucity of studies on well-characterized real-life DE exposure in humans. In the present study, 29 healthy volunteers were exposed to DE while sitting as passengers in diesel-powered trains. Exposure in electric trains was used as control scenario. Each train scenario consisted of three consecutive days (6 h/day) ending with biomarker samplings. RESULTS: Combustion-derived air pollutants were considerably higher in the passenger carriages of diesel trains compared with electric trains. The concentrations of black carbon and ultrafine particles were 8.5 µg/m3 and 1.2-1.8 × 105 particles/cm3 higher, respectively, in diesel as compared to electric trains. Net increases of NOx and NO2 concentrations were 317 µg/m3 and 36 µg/m3. Exposure to DE was associated with reduced lung function and increased levels of DNA strand breaks in peripheral blood mononuclear cells (PBMCs), whereas there were unaltered levels of oxidatively damaged DNA, soluble cell adhesion molecules, acute phase proteins in blood and urinary excretion of metabolites of polycyclic aromatic hydrocarbons. Also the microvascular function was unaltered. An increase in the low frequency of heart rate variability measures was observed, whereas time-domain measures were unaltered. CONCLUSION: Exposure to DE inside diesel-powered trains for 3 days was associated with reduced lung function and systemic effects in terms of altered heart rate variability and increased levels of DNA strand breaks in PBMCs compared with electric trains. TRIAL REGISTRATION: ClinicalTrials.Gov ( NCT03104387 ). Registered on March 23rd 2017.

Indoor dispersion of airborne nano and fine particles: Main factors affecting spatial and temporal distribution in the frame of exposure modeling.

A particle exposure experiment inside a large climate-controlled chamber was conducted. Data on spatial and temporal distribution of nanoscale and fine aerosols in the range of mobility diameters 8-600 nm were collected with high resolution, for sodium chloride, fluorescein sodium, and silica particles. Exposure scenarios studied included constant and intermittent source emissions, different aggregation conditions, high (10 h-1 ) and low (3.5 h-1 ) air exchange rates (AERs) corresponding to chamber Reynolds number, respectively, equal to 1 × 105 and 3 × 104 . Results are presented and analyzed to highlight the main determinants of exposure and to determine whether the assumptions underlying two-box models hold under various scenarios. The main determinants of exposure found were the source generation rate and the ventilation rate. The effect of particles nature was indiscernible, and the decrease of airborne total number concentrations attributable to surface deposition was estimated lower than 2% when the source was active. A near-field/far-field structure of aerosol concentration was always observed for the AER = 10 h-1 but for AER = 3.5 h-1 , a single-field structure was found. The particle size distribution was always homogeneous in space but a general shift of particle diameter (-8% to +16%) was observed between scenarios in correlation with the AER and with the source position, presumably largely attributable to aggregation.

Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring.

BACKGROUND: Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90). METHODS: Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test. RESULTS: Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 28-29 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated. CONCLUSION: The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders.

The general ventilation multipliers calculated by using a standard Near-Field/Far-Field model.

In conceptual exposure models, the transmission of pollutants in an imperfectly mixed room is usually described with general ventilation multipliers. This is the approach used in the Advanced REACH Tool (ART) and Stoffenmanager® exposure assessment tools. The multipliers used in these tools were reported by Cherrie (1999; http://dx.doi.org/10.1080/104732299302530 ) and Cherrie et al. (2011; http://dx.doi.org/10.1093/annhyg/mer092 ) who developed them by positing input values for a standard Near-Field/Far-Field (NF/FF) model and then calculating concentration ratios between NF and FF concentrations. This study revisited the calculations that produce the multipliers used in ART and Stoffenmanager and found that the recalculated general ventilation multipliers were up to 2.8 times (280%) higher than the values reported by Cherrie (1999) and the recalculated NF and FF multipliers for 1-hr exposure were up to 1.2 times (17%) smaller and for 8-hr exposure up to 1.7 times (41%) smaller than the values reported by Cherrie et al. (2011). Considering that Stoffenmanager and the ART are classified as higher-tier regulatory exposure assessment tools, the errors is general ventilation multipliers should not be ignored. We recommend revising the general ventilation multipliers. A better solution is to integrate the NF/FF model to Stoffenmanager and the ART.

A Proposed In Vitro Method to Assess Effects of Inhaled Particles on Lung Surfactant Function.

The lung surfactant (LS) lining is a thin liquid film covering the air-liquid interface of the respiratory tract. LS reduces surface tension, enabling lung surface expansion and contraction with minimal work during respiration. Disruption of surface tension is believed to play a key role in severe lung conditions. Inhalation of aerosols that interfere with the LS may induce a toxic response and, as a part of the safety assessment of chemicals and inhaled medicines, it may be relevant to study their impact on LS function. Here, we present a novel in vitro method, based on the constrained drop surfactometer, to study LS functionality after aerosol exposure. The applicability of the method was investigated using three inhaled asthma medicines, micronized lactose, a pharmaceutical excipient used in inhaled medication, and micronized albumin, a known inhibitor of surfactant function. The surfactometer was modified to allow particles mixed in air to flow through the chamber holding the surfactant drop. The deposited dose was measured with a custom-built quartz crystal microbalance. The alterations allowed the study of continuously increasing quantified doses of particles, allowing determination of the dose of particles that affects the LS function. The tested pharmaceuticals did not inhibit the function of a model LS even at extreme doses--neither did lactose. Micronized albumin, however, impaired surfactant function. The method can discriminate between safe inhaled aerosols--as exemplified by the approved inhaled medicines and the pharmaceutical excipient lactose--and albumin known to impair lung functionality by inhibiting LS function.

Generation and Characterization of Indoor Fungal Aerosols for Inhalation Studies.

In the indoor environment, people are exposed to several fungal species. Evident dampness is associated with increased respiratory symptoms. To examine the immune responses associated with fungal exposure, mice are often exposed to a single species grown on an agar medium. The aim of this study was to develop an inhalation exposure system to be able to examine responses in mice exposed to mixed fungal species aerosolized from fungus-infested building materials. Indoor airborne fungi were sampled and cultivated on gypsum boards. Aerosols were characterized and compared with aerosols in homes. Aerosols containing 10(7)CFU of fungi/m(3)air were generated repeatedly from fungus-infested gypsum boards in a mouse exposure chamber. Aerosols contained Aspergillus nidulans,Aspergillus niger, Aspergillus ustus, Aspergillus versicolor,Chaetomium globosum,Cladosporium herbarum,Penicillium brevicompactum,Penicillium camemberti,Penicillium chrysogenum,Penicillium commune,Penicillium glabrum,Penicillium olsonii,Penicillium rugulosum,Stachybotrys chartarum, and Wallemia sebi They were all among the most abundant airborne species identified in 28 homes. Nine species from gypsum boards and 11 species in the homes are associated with water damage. Most fungi were present as single spores, but chains and clusters of different species and fragments were also present. The variation in exposure level during the 60 min of aerosol generation was similar to the variation measured in homes. Through aerosolization of fungi from the indoor environment, cultured on gypsum boards, it was possible to generate realistic aerosols in terms of species composition, concentration, and particle sizes. The inhalation-exposure system can be used to study responses to indoor fungi associated with water damage and the importance of fungal species composition.

Comparison of dust release from epoxy and paint nanocomposites and conventional products during sanding and sawing.

The release of dust generated during sanding or sawing of nanocomposites was compared with conventional products without nanomaterials. Epoxy-based polymers with and without carbon nanotubes, and paints with different amounts of nano-sized titanium dioxide, were machined in a closed aerosol chamber. The temporal evolution of the aerosol concentration and size distribution were measured simultaneously. The morphology of collected dust by scanning electron microscopy was different depending on the type of nanocomposites: particles from carbon nanotubes (CNTs) nanocomposites had protrusions on their surfaces and aggregates and agglomerates are attached to the paint matrix in particles emitted from alkyd paints. We observed no significant differences in the particle size distributions when comparing sanding dust from nanofiller containing products with dust from conventional products. Neither did we observe release of free nanomaterials. Instead, the nanomaterials were enclosed or partly enclosed in the matrix. A source strength term Si (cm(-3) s(-1)) that describes particle emission rates from continuous sources was introduced. Comparison between the Si parameters derived from sanding different materials allows identification of potential effects of addition of engineered nanoparticles to a composite.

Exposure assessment of four pharmaceutical powders based on dustiness and evaluation of damaged HEPA filters.

In this study, we show the different dustiness characteristics of four molecular pharmaceutical powder candidates and evaluate the performance of HEPA filters damaged with three different pinhole sizes and exposed to dust using real industrial powders in a miniaturized EN15051 rotating drum dustiness tester. We then demonstrate the potential use of such data using first-order exposure modeling to assess the potential worker exposure and transmission of active powder ingredients into ventilation systems. The four powders had highly variable inhalable dustiness indices (1,036 - 14,501 mg/kg). Dust particle size-distributions were characterized by three peaks; the first occurred around 60-80 nm, the second around 250 nm, and the third at 2-3 µm. The second and third peaks are often observed in dustiness test studies, but peaks in the 60-80 nm range have not been previously reported. Exposure modeling in a 5 times 20 kg powder pouring scenario, suggests that excessive dust concentrations may be reached during use of powders with the highest dustiness levels. By number, filter-damage by three pinhole sizes resulted in damage-dependent penetration of 70-80 nm-size particles, but by volume and mass the penetration is still dominated by particles larger than 100 nm. Whereas the exposure potential was evident, the potential dust concentrations in air ducts following the pouring scenario above were at pg/m(3) levels. Hence, filter penetration at these damage levels was assumed to be only critical, if the active ingredients were associated with high hazard or unique product purity is required. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resource: An example of a typical particle number time-series of a complete dustiness test. It provides information on the HEPA-filter used including a scanning electron microscopy image of it. It also provides APS-measurements of particles penetrating the damaged HEPA-filter.].

Nanotitanium dioxide toxicity in mouse lung is reduced in sanding dust from paint.

BACKGROUND: Little is known of how the toxicity of nanoparticles is affected by the incorporation in complex matrices. We compared the toxic effects of the titanium dioxide nanoparticle UV-Titan L181 (NanoTiO2), pure or embedded in a paint matrix. We also compared the effects of the same paint with and without NanoTiO2. METHODS: Mice received a single intratracheal instillation of 18, 54 and 162 µg of NanoTiO2 or 54, 162 and 486 µg of the sanding dust from paint with and without NanoTiO2. DNA damage in broncheoalveolar lavage cells and liver, lung inflammation and liver histology were evaluated 1, 3 and 28 days after intratracheal instillation. Printex 90 was included as positive control. RESULTS: There was no additive effect of adding NanoTiO2 to paints: Therefore the toxicity of NanoTiO2 was reduced by inclusion into a paint matrix. NanoTiO2 induced inflammation in mice with severity similar to Printex 90. The inflammatory response of NanoTiO2 and Printex 90 correlated with the instilled surface area. None of the materials, except of Printex 90, induced DNA damage in lung lining fluid cells. The highest dose of NanoTiO2 caused DNA damage in hepatic tissue 1 day after intratracheal instillation. Exposure of mice to the dust from paints with and without TiO2 was not associated with hepatic histopathological changes. Exposure to NanoTiO2 or to Printex 90 caused slight histopathological changes in the liver in some of the mice at different time points. CONCLUSIONS: Pulmonary inflammation and DNA damage and hepatic histopathology were not changed in mice instilled with sanding dust from NanoTiO2 paint compared to paint without NanoTiO2. However, pure NanoTiO2 caused greater inflammation than NanoTiO2 embedded in the paint matrix.

Evaluating the Theoretical Background of STOFFENMANAGER® and the Advanced REACH Tool.

STOFFENMANAGER® and the Advanced REACH Tool (ART) are recommended tools by the European Chemical Agency for regulatory chemical safety assessment. The models are widely used and accepted within the scientific community. STOFFENMANAGER® alone has more than 37 000 users globally and more than 310 000 risk assessment have been carried out by 2020. Regardless of their widespread use, this is the first study evaluating the theoretical backgrounds of each model. STOFFENMANAGER® and ART are based on a modified multiplicative model where an exposure base level (mg m-3) is replaced with a dimensionless intrinsic emission score and the exposure modifying factors are replaced with multipliers that are mainly based on subjective categories that are selected by using exposure taxonomy. The intrinsic emission is a unit of concentration to the substance emission potential that represents the concentration generated in a standardized task without local ventilation. Further information or scientific justification for this selection is not provided. The multipliers have mainly discrete values given in natural logarithm steps (…, 0.3, 1, 3, …) that are allocated by expert judgements. The multipliers scientific reasoning or link to physical quantities is not reported. The models calculate a subjective exposure score, which is then translated to an exposure level (mg m-3) by using a calibration factor. The calibration factor is assigned by comparing the measured personal exposure levels with the exposure score that is calculated for the respective exposure scenarios. A mixed effect regression model was used to calculate correlation factors for four exposure group [e.g. dusts, vapors, mists (low-volatiles), and solid object/abrasion] by using ~1000 measurements for STOFFENMANAGER® and 3000 measurements for ART. The measurement data for calibration are collected from different exposure groups. For example, for dusts the calibration data were pooled from exposure measurements sampled from pharmacies, bakeries, construction industry, and so on, which violates the empirical model basic principles. The calibration databases are not publicly available and thus their quality or subjective selections cannot be evaluated. STOFFENMANAGER® and ART can be classified as subjective categorization tools providing qualitative values as their outputs. By definition, STOFFENMANAGER® and ART cannot be classified as mechanistic models or empirical models. This modeling algorithm does not reflect the physical concept originally presented for the STOFFENMANAGER® and ART. A literature review showed that the models have been validated only at the 'operational analysis' level that describes the model usability. This review revealed that the accuracy of STOFFENMANAGER® is in the range of 100 000 and for ART 100. Calibration and validation studies have shown that typical log-transformed predicted exposure concentration and measured exposure levels often exhibit weak Pearson's correlations (r is <0.6) for both STOFFENMANAGER® and ART. Based on these limitations and performance departure from regulatory criteria for risk assessment models, it is recommended that STOFFENMANAGER® and ART regulatory acceptance for chemical safety decision making should be explicitly qualified as to their current deficiencies.

Particle emission rates during electrostatic spray deposition of TiO2 nanoparticle-based photoactive coating.

Here, we studied the particle release rate during Electrostatic spray deposition of anatase-(TiO2)-based photoactive coating onto tiles and wallpaper using a commercially available electrostatic spray device. Spraying was performed in a 20.3m3 test chamber while measuring concentrations of 5.6nm to 31µm-size particles and volatile organic compounds (VOC), as well as particle deposition onto room surfaces and on the spray gun user hand. The particle emission and deposition rates were quantified using aerosol mass balance modelling. The geometric mean particle number emission rate was 1.9×1010s-1 and the mean mass emission rate was 381µgs-1. The respirable mass emission-rate was 65% lower than observed for the entire measured size-range. The mass emission rates were linearly scalable (±ca. 20%) to the process duration. The particle deposition rates were up to 15h-1 for <1µm-size and the deposited particles consisted of mainly TiO2, TiO2 mixed with Cl and/or Ag, TiO2 particles coated with carbon, and Ag particles with size ranging from 60nm to ca. 5µm. As expected, no significant VOC emissions were observed as a result of spraying. Finally, we provide recommendations for exposure model parameterization.

Particle release and control of worker exposure during laboratory-scale synthesis, handling and simulated spills of manufactured nanomaterials in fume hoods.

Fume hoods are one of the most common types of equipment applied to reduce the potential of particle exposure in laboratory environments. A number of previous studies have shown particle release during work with nanomaterials under fume hoods. Here, we assessed laboratory workers' inhalation exposure during synthesis and handling of CuO, TiO2 and ZnO in a fume hood. In addition, we tested the capacity of a fume hood to prevent particle release to laboratory air during simulated spillage of different powders (silica fume, zirconia TZ-3Y and TiO2). Airborne particle concentrations were measured in near field, far field, and in the breathing zone of the worker. Handling CuO nanoparticles increased the concentration of small particles (< 58 nm) inside the fume hood (up to 1 × 105 cm-3). Synthesis, handling and packaging of ZnO and TiO2 nanoparticles did not result in detectable particle release to the laboratory air. Simulated powder spills showed a systematic increase in the particle concentrations inside the fume hood with increasing amount of material and drop height. Despite powder spills were sometimes observed to eject into the laboratory room, the spill events were rarely associated with notable release of particles from the fume hood. Overall, this study shows that a fume hood generally offers sufficient exposure control during synthesis and handling of nanomaterials. An appropriate fume hood with adequate sash height and face velocity prevents 98.3% of particles release into the surrounding environment. Care should still be made to consider spills and high cleanliness to prevent exposure via resuspension and inadvertent exposure by secondary routes.

Bile salt enhancers for inhalation: Correlation between in vitro and in vivo lung effects.

The lungs have potential as a means of systemic drug delivery of macromolecules. Systemic delivery requires crossing of the air-blood barrier, however with molecular size-dependent limitations in lung absorption of large molecules. Systemic availability after inhalation can be improved by absorption enhancers, such as bile salts. Enhancers may potentially interfere with the different constituents of the lungs, e.g. the lung surfactant lining the alveoli or the lung epithelium. We used two in vitro models to investigate the potential effects of bile salts on lung surfactant function (with the constrained drop surfactometer) and on the epithelium in the proximal airways (with the MucilAir™ cell system), respectively. In addition, we measured direct effects on respiration in mice inhaling bile salt aerosols. The bile salts inhibited lung surfactant function at different dose levels, however they did not affect the integrity of ciliated cells at the tested doses. Furthermore, the bile salt aerosols induced changes in the breathing pattern of mice indicative of pulmonary irritation. The bile salts were ranked according to potency in vitro for surfactant function disruption and in vivo for induction of pulmonary irritation. The ranking was the same, suggesting a correlation between the interference with lung surfactant and the respiratory response.

A simple procedure for correcting loading effects of aethalometer data.

A simple method for correcting for the loading effects of aethalometer data is presented. The formula BC(CORRECTED) = (1 + k x ATN) x BC(NONCORRECTED), where ATN is the attenuation and BC is black carbon, was used for correcting aethalometer data obtained from measurements at three different sites: a subway station in Helsinki, an urban background measurement station in Helsinki, and a rural station in Hyytiälä in central Finland. The BC data were compared with simultaneously measured aerosol volume concentrations (V). After the correction algorithm, the BC-to-V ratio remained relatively stable between consequent filter spots, which can be regarded as indirect evidence that the correction algorithm works. The k value calculated from the outdoor sites had a clear seasonal cycle that could be explained by darker aerosol in winter than in summer. When the contribution of BC to the total aerosol volume was high, the k factor was high and vice versa. In winter, the k values at all wavelengths were very close to that obtained from the subway station data. In summer, the k value was wavelength dependent and often negative. When the k value is negative, the noncorrected BC concentrations overestimated the true concentrations.

Pulmonary injury associated with spray of a water-based nano-sized waterproofing product: a case study.

BACKGROUND: In most reported cases of lung trauma with water proofing products, volatile organic compounds (VOC) have a prominent role. Here we report on a case involving ten workers exposed to a sprayed product containing nanoparticles in a water solution with only a few percent VOC. CASE PRESENTATION: Ten workers suffered from respiratory symptoms following spray impregnation of hardwood furniture using a waterproofing product that contained positively charged fluorinated acrylate copolymer solid cores with a median diameter of 70 nm (1.3 w%) in aqueous suspension with 3.3 w% VOC and 0.3 w% quaternary ammonium. The worker who applied one liter of the product in a wood workshop, using an air mix spray gun, did not report any health complaints. Another worker, who entered the workshop 3 h later and had rolled and smoked two cigarettes, was hospitalized with severe chemical pneumonitis. A chest X-ray (CXR) showed bilateral infiltrative impairment in the lower lobe regions. On the next day a second CXR showed increased patchiness marking in all fields. A high-resolution Computer Tomography (CT)-scan demonstrated extensive bilateral areas of ground-glass opacities predominantly in the lower regions of the upper lobes, the right middle lobe and the apical regions of the lower lobes, compatible with severe chemical pneumonitis. On the following morning, nine workers in an adjacent workplace in the same building, experienced dry cough, chest tightness and substernal pain upon physical exercise. Reconstruction of the spray application in a climate chamber confirmed trimethyl silanol, glycol ethers and fluoroalkenes in the gas phase. Immediately after the spray application, aerosols were observed at a maximum concentration of 6.3 × 104 cm-3. Mass concentrations were 0.095 and 10 mg/m3 in the size ranges 5.6-560 nm and 0.22-30 µm, respectively, decreasing to less than 10 µg/m3 in both size ranges after 15 h. CONCLUSION: The hospitalized worker had smoked cigarettes contaminated with fluoropolymers which is a plausible explanation for the lung trauma. Respiratory symptoms in the nine workers may be caused by inhalation of particles that became airborne by resuspension from surfaces when workers entered the adjacent workplace the next day. A contribution from VOC appears less likely because measurements and modelling showed that concentrations in the mg/m3 range could have occurred only if the building was assumed to be completely airtight.

Differences in inflammation and acute phase response but similar genotoxicity in mice following pulmonary exposure to graphene oxide and reduced graphene oxide.

We investigated toxicity of 2-3 layered >1 µm sized graphene oxide (GO) and reduced graphene oxide (rGO) in mice following single intratracheal exposure with respect to pulmonary inflammation, acute phase response (biomarker for risk of cardiovascular disease) and genotoxicity. In addition, we assessed exposure levels of particulate matter emitted during production of graphene in a clean room and in a normal industrial environment using chemical vapour deposition. Toxicity was evaluated at day 1, 3, 28 and 90 days (18, 54 and 162 µg/mouse), except for GO exposed mice at day 28 and 90 where only the lowest dose was evaluated. GO induced a strong acute inflammatory response together with a pulmonary (Serum-Amyloid A, Saa3) and hepatic (Saa1) acute phase response. rGO induced less acute, but a constant and prolonged inflammation up to day 90. Lung histopathology showed particle agglomerates at day 90 without signs of fibrosis. In addition, DNA damage in BAL cells was observed across time points and doses for both GO and rGO. In conclusion, pulmonary exposure to GO and rGO induced inflammation, acute phase response and genotoxicity but no fibrosis.