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.

Characterization of particle exposure in ferrochromium and stainless steel production.

This study describes workers' exposure to fine and ultrafine particles in the production chain of ferrochromium and stainless steel during sintering, ferrochromium smelting, stainless steel melting, and hot and cold rolling operations. Workers' personal exposure to inhalable dust was assessed using IOM sampler with a cellulose acetate filter (AAWP, diameter 25 mm; Millipore, Bedford, MA). Filter sampling methods were used to measure particle mass concentrations in fixed locations. Particle number concentrations and size distributions were examined using an SMPS+C sequential mobile particle sizer and counter (series 5.400, Grimm Aerosol Technik, Ainring, Germany), and a hand-held condensation particle counter (CPC, model 3007, TSI Incorporated, MN). The structure and elemental composition of particles were analyzed using TEM-EDXA (TEM: JEM-1220, JEOL, Tokyo, Japan; EDXA: Noran System Six, Thermo Fisher Scientific Inc., Madison,WI). Workers' personal exposure to inhalable dust averaged 1.87, 1.40, 2.34, 0.30, and 0.17 mg m(-3) in sintering plant, ferrochromium smelter, stainless steel melting shop, hot rolling mill, and the cold rolling mill, respectively. Particle number concentrations measured using SMPS+C varied from 58 × 10(3) to 662 × 10(3) cm(-3) in the production areas, whereas concentrations measured using SMPS+C and CPC3007 in control rooms ranged from 24 × 10(3) to 243 × 10(3) cm(-3) and 5.1 × 10(3) to 97 × 10(3) cm(-3), respectively. The elemental composition and the structure of particles in different production phases varied. In the cold-rolling mill non-process particles were abundant. In other sites, chromium and iron originating from ore and recycled steel scrap were the most common elements in the particles studied. Particle mass concentrations were at the same level as that reported earlier. However, particle number measurements showed a high amount of ultrafine particles, especially in sintering, alloy smelting and melting, and tapping operations. Particle number concentration and size distribution measurements provide important information regarding exposure to ultrafine particles, which cannot be seen in particle mass measurements.

Characterization of exposure to carbon nanotubes in an industrial setting.

While production and use of carbon nanotubes (CNTs) is increasing, workers exposure to CNTs is expected to increase as well, with inhalation being potentially the main pathway for uptake. However, there have been few studies reporting results about workers' personal exposure to CNTs. In this study, worker exposure to single-walled CNTs (SWCNTs) during the production of conductive films in a modern up-scaling factory was assessed. Particulate matter concentrations (2.5-10 µm) and concentrations of CO and CO2 were monitored by using real-time instruments. Workers' exposure levels to SWCNTs were qualitatively estimated by analyzing particle samples by transmission electron microscopy (TEM). TEM samples identified high aspect ratio (length/width > 500) SWCNTs in workplace air. SWCNT concentrations estimated from micrographs varied during normal operation, reactor use without local exhaust ventilation (LEV), and cleaning between 1.7×10(-3), 5.6 and 6.0×10(-3) SWCNT cm(-3), respectively. However, during cleaning it was unclear whether the SWCNTs originated from the cleaning itself or from other reactor openings. We were unable to quantify the SWCNT emissions with online particle instrumentation due to the SWCNT low concentrations compared to background particle concentrations, which were on average 2.6±1.1×10(3)cm(-3). However, CO concentrations were verified as a good indicator of fugitive emissions of SWCNTs. During normal operation, exposure levels were well below proposed limit values (1.0×10(-2) fibers cm(-3) and 1 µg m(-3)) when LEV was used. Based on the results in this study, the analysis of TEM grids seems to be the only direct method to detect SWCNTs in workplace air.

Inhalation of rod-like carbon nanotubes causes unconventional allergic airway inflammation.

BACKGROUND: Carbon nanotubes (CNT) represent a great promise for technological and industrial development but serious concerns on their health effects have also emerged. Rod-shaped CNT are, in fact, able to induce asbestos-like pathogenicity in mice including granuloma formation in abdominal cavity and sub-pleural fibrosis. Exposure to CNT, especially in the occupational context, happens mainly by inhalation. However, little is known about the possible effects of CNT on pulmonary allergic diseases, such as asthma. METHODS: We exposed mice by inhalation to two types of multi-walled CNT, rigid rod-like and flexible tangled CNT, for four hours a day once or on four consecutive days. Early events were monitored immediately and 24 hours after the single inhalation exposure and the four day exposure mimicked an occupational work week. Mast cell deficient mice were used to evaluate the role of mast cells in the occurring inflammation. RESULTS: Here we show that even a short-term inhalation of the rod-like CNT induces novel innate immunity-mediated allergic-like airway inflammation in healthy mice. Marked eosinophilia was accompanied by mucus hypersecretion, AHR and the expression of Th2-type cytokines. Exploration of the early events by transcriptomics analysis reveals that a single 4-h exposure to rod-shaped CNT, but not to tangled CNT, causes a radical up-regulation of genes involved in innate immunity and cytokine/chemokine pathways. Mast cells were found to partially regulate the inflammation caused by rod-like CNT, but also alveaolar macrophages play an important role in the early stages. CONCLUSIONS: These observations emphasize the diverse abilities of CNT to impact the immune system, and they should be taken into account for hazard assessment.

Genotoxicity of inhaled nanosized TiO(2) in mice.

In vitro studies have suggested that nanosized titanium dioxide (TiO(2)) is genotoxic. The significance of these findings with respect to in vivo effects is unclear, as few in vivo studies on TiO(2) genotoxicity exist. Recently, nanosized TiO(2) administered in drinking water was reported to increase, e.g., micronuclei (MN) in peripheral blood polychromatic erythrocytes (PCEs) and DNA damage in leukocytes. Induction of micronuclei in mouse PCEs was earlier also described for pigment-grade TiO(2) administered intraperitoneally. The apparent systemic genotoxic effects have been suggested to reflect secondary genotoxicity of TiO(2) due to inflammation. However, a recent study suggested that induction of DNA damage in mouse bronchoalveolar lavage (BAL) cells after intratracheal instillation of nanosized or fine TiO(2) is independent of inflammation. We examined here, if inhalation of freshly generated nanosized TiO(2) (74% anatase, 26% brookite; 5 days, 4 h/day) at 0.8, 7.2, and (the highest concentration allowing stable aerosol production) 28.5 mg/m(3) could induce genotoxic effects in C57BL/6J mice locally in the lungs or systematically in peripheral PCEs. DNA damage was assessed by the comet assay in lung epithelial alveolar type II and Clara cells sampled immediately following the exposure. MN were analyzed by acridine orange staining in blood PCEs collected 48 h after the last exposure. A dose-dependent deposition of Ti in lung tissue was seen. Although the highest exposure level produced a clear increase in neutrophils in BAL fluid, indicating an inflammatory effect, no significant effect on the level of DNA damage in lung epithelial cells or micronuclei in PCEs was observed, suggesting no genotoxic effects by the 5-day inhalation exposure to nanosized TiO(2) anatase. Our inhalation exposure resulted in much lower systemic TiO(2) doses than the previous oral and intraperitoneal treatments, and lung epithelial cells probably received considerably less TiO(2) than BAL cells in the earlier intratracheal study.

Inhalation exposure to nanosized and fine TiO2 particles inhibits features of allergic asthma in a murine model.

BACKGROUND: Nanotechnology and engineered nanomaterials (ENM) are here to stay. Recent evidence suggests that exposure to environmental particulate matter exacerbates symptoms of asthma. In the present study we investigated the modulatory effects of titanium dioxide particle exposure in an experimental allergic asthma. METHODS: Nonallergic (healthy) and ovalbumin-sensitized (asthmatic) mice were exposed via inhalation to two different sizes of titanium dioxide particles, nanosized (nTiO2) and fine (fTiO2), for 2 hours a day, three days a week, for four weeks at a concentration of 10 mg/m3. Different endpoints were analysed to evaluate the immunological status of the mice. RESULTS: Healthy mice elicited pulmonary neutrophilia accompanied by significantly increased chemokine CXCL5 expression when exposed to nTiO2. Surprisingly, allergic pulmonary inflammation was dramatically suppressed in asthmatic mice which were exposed to nTiO2 or fTiO2 particles - i.e. the levels of leucocytes, cytokines, chemokines and antibodies characteristic to allergic asthma were substantially decreased. CONCLUSIONS: Our results suggest that repeated airway exposure to TiO2 particles modulates the airway inflammation depending on the immunological status of the exposed mice.

Modeling of High Nanoparticle Exposure in an Indoor Industrial Scenario with a One-Box Model.

Mass balance models have proved to be effective tools for exposure prediction in occupational settings. However, they are still not extensively tested in real-world scenarios, or for particle number concentrations. An industrial scenario characterized by high emissions of unintentionally-generated nanoparticles (NP) was selected to assess the performance of a one-box model. Worker exposure to NPs due to thermal spraying was monitored, and two methods were used to calculate emission rates: the convolution theorem, and the cyclic steady state equation. Monitored concentrations ranged between 4.2 × 104-2.5 × 105 cm-3. Estimated emission rates were comparable with both methods: 1.4 × 1011-1.2 × 1013 min-1 (convolution) and 1.3 × 1012-1.4 × 1013 min-1 (cyclic steady state). Modeled concentrations were 1.4-6 × 104 cm-3 (convolution) and 1.7-7.1 × 104 cm-3 (cyclic steady state). Results indicated a clear underestimation of measured particle concentrations, with ratios modeled/measured between 0.2-0.7. While both model parametrizations provided similar results on average, using convolution emission rates improved performance on a case-by-case basis. Thus, using cyclic steady state emission rates would be advisable for preliminary risk assessment, while for more precise results, the convolution theorem would be a better option. Results show that one-box models may be useful tools for preliminary risk assessment in occupational settings when room air is well mixed.

Testing the performance of one and two box models as tools for risk assessment of particle exposure during packing of inorganic fertilizer.

Modelling of particle exposure is a useful tool for preliminary exposure assessment in workplaces with low and high exposure concentrations. However, actual exposure measurements are needed to assess models reliability. Worker exposure was monitored during packing of an inorganic granulate fertilizer at industrial scale using small and big bags. Particle concentrations were modelled with one and two box models, where the emission source was estimated with the fertilizer's dustiness index. The exposure levels were used to calculate inhaled dose rates and test accuracy of the exposure modellings. The particle number concentrations were measured from worker area by using a mobility and optical particle sizer which were used to calculate surface area and mass concentrations. The concentrations in the worker area during pre-activity ranged 63,797-81,073 cm-3, 4.6 × 106 to 7.5 × 106 µm2 cm-3, and 354 to 634 µg m-3 (respirable mass fraction) and during packing 50,300 to 85,949 cm-3, 4.3 × 106 to 7.6 × 106 µm2 cm-3, and 279 to 668 µg m-3 (respirable mass fraction). Thus, the packing process did not significantly increase the exposure levels. Chemical exposure was also under control based on REACH standards. The particle surface area deposition rate in respiratory tract was up to 7.6 × 106 µm2 min-1 during packing, with 52%-61% of deposition occurring in the alveolar region. Ratios of the modelled and measured concentrations were 0.98 ±â€¯0.19 and 0.84 ±â€¯0.12 for small and big bags, respectively, when using the one box model, and 0.88 ±â€¯0.25 and 0.82 ±â€¯0.12, when using the two box model. The modelling precision improved for both models when outdoor particle concentrations were included. This study shows that exposure concentrations in a low emission industrial scenario, e.g. during packing of a fertilizer, can be predicted with a reasonable accuracy by using the concept of dustiness and mass balance models.

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.

Safety Assessment of Graphene-Based Materials: Focus on Human Health and the Environment.

Graphene and its derivatives are heralded as "miracle" materials with manifold applications in different sectors of society from electronics to energy storage to medicine. The increasing exploitation of graphene-based materials (GBMs) necessitates a comprehensive evaluation of the potential impact of these materials on human health and the environment. Here, we discuss synthesis and characterization of GBMs as well as human and environmental hazard assessment of GBMs using in vitro and in vivo model systems with the aim to understand the properties that underlie the biological effects of these materials; not all GBMs are alike, and it is essential that we disentangle the structure-activity relationships for this class of materials.

Workplace Measurements of Ultrafine Particles-A Literature Review.

Workers are exposed to ultrafine particles (UFP) in a number of occupations. In order to summarize the current knowledge regarding occupational exposure to UFP (excluding engineered nanoparticles), we gathered information on UFP concentrations from published research articles. The aim of our study was to create a basis for future epidemiological studies that treat UFP as an exposure factor. The literature search found 72 publications regarding UFP measurements in work environments. These articles covered 314 measurement results and tabled concentrations. Mean concentrations were compared to typical urban UFP concentration level, which was considered non-occupational background concentration. Mean concentrations higher than the typical urban UFP concentration were reported in 240 workplace measurements. The results showed that workers' exposure to UFP may be significantly higher than their non-occupational exposure to background concentration alone. Mean concentrations of over 100 times the typical urban UFP concentration were reported in welding and metal industry. However, according to the results of the review, measurements of the UFP in work environments are, to date, too limited and reported too heterogeneous to allow us to draw general conclusions about workers' exposure. Harmonization of measurement strategies is essential if we are to generate more reliable and comparable data in the future.

In vitro and in vivo genotoxic effects of straight versus tangled multi-walled carbon nanotubes.

Some multi-walled carbon nanotubes (MWCNTs) induce mesothelioma in rodents, straight MWCNTs showing a more pronounced effect than tangled MWCNTs. As primary and secondary genotoxicity may play a role in MWCNT carcinogenesis, we used a battery of assays for DNA damage and micronuclei to compare the genotoxicity of straight (MWCNT-S) and tangled MWCNTs (MWCNT-T) in vitro (primary genotoxicity) and in vivo (primary or secondary genotoxicity). C57Bl/6 mice showed a dose-dependent increase in DNA strand breaks, as measured by the comet assay, in lung cells 24 h after a single pharyngeal aspiration of MWCNT-S (1-200 µg/mouse). An increase was also observed for DNA strand breaks in lung and bronchoalveolar lavage (BAL) cells and for micronucleated alveolar type II cells in mice exposed to aerosolized MWCNT-S (8.2-10.8 mg/m(3)) for 4 d, 4 h/d. No systemic genotoxic effects, assessed by the γ-H2AX assay in blood mononuclear leukocytes or by micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow or blood, were observed for MWCNT-S by either exposure technique. MWCNT-T showed a dose-related decrease in DNA damage in BAL and lung cells of mice after a single pharyngeal aspiration (1-200 µg/mouse) and in MNPCEs after inhalation exposure (17.5 mg/m(3)). In vitro in human bronchial epithelial BEAS-2B cells, MWCNT-S induced DNA strand breaks at low doses (5 and 10 µg/cm(2)), while MWCNT-T increased strand breakage only at 200 µg/cm(2). Neither of the MWCNTs was able to induce micronuclei in vitro. Our findings suggest that both primary and secondary mechanisms may be involved in the genotoxicity of straight MWCNTs.

Range-finding risk assessment of inhalation exposure to nanodiamonds in a laboratory environment.

This study considers fundamental methods in occupational risk assessment of exposure to airborne engineered nanomaterials. We discuss characterization of particle emissions, exposure assessment, hazard assessment with in vitro studies, and risk range characterization using calculated inhaled doses and dose-response translated to humans from in vitro studies. Here, the methods were utilized to assess workers' risk range of inhalation exposure to nanodiamonds (NDs) during handling and sieving of ND powder. NDs were agglomerated to over 500 nm particles, and mean exposure levels of different work tasks varied from 0.24 to 4.96 µg·m(-3) (0.08 to 0.74 cm(-3)). In vitro-experiments suggested that ND exposure may cause a risk for activation of inflammatory cascade. However, risk range characterization based on in vitro dose-response was not performed because accurate assessment of delivered (settled) dose on the cells was not possible. Comparison of ND exposure with common pollutants revealed that ND exposure was below 5 µg·m(-3), which is one of the proposed exposure limits for diesel particulate matter, and the workers' calculated dose of NDs during the measurement day was 74 ng which corresponded to 0.02% of the modeled daily (24 h) dose of submicrometer urban air particles.

Concept to estimate regional inhalation dose of industrially synthesized nanoparticles.

The use of nanoparticles (NPs) in industry is increasing rapidly, but knowledge of the occupational health and safety aspects of NPs is still limited. This is because quantitative NP exposure levels are scarce, and the metrics to describe doses are unclear. This study presents one method for estimating workers' calculated regional inhalation dose of deposited particles from size-fractionated concentrations. It was applied to estimate workers' regional inhalation dose rates and doses separately for NPs and NPs with background particles during NP synthesis. Dose analysis was performed in units of particle number (particles and particles min(-1)), active surface area (µm(2) and µm(2) min(-1)), and mass (ng and ng min(-1)) for three respiratory regions: head airways, tracheobronchial, and alveolar. It was found that in NP synthesis NPs were deposited mainly in the alveolar region in all units. However, when the dose of all particles was examined, it was found that dose and the main deposition region were mainly defined by the synthesized NPs for particle number, as active surface area was described by both NPs and background particles, and mass by background particles. This study provides fundamental data for NP inhalation exposure risk assessment, regulations, dose metrics for NP synthesis, and a basis for defining metrics of dose-biological response and helps us understand the magnitude of doses in NP synthesis. It also illustrates the necessity to obtain size-fractionated measurements of NP concentrations to support accurate dose estimation.

Airway exposure to silica-coated TiO2 nanoparticles induces pulmonary neutrophilia in mice.

The importance of nanotechnologies and engineered nanoparticles has grown rapidly. It is therefore crucial to acquire up-to-date knowledge of the possible harmful health effects of these materials. Since a multitude of different types of nanosized titanium dioxide (TiO(2)) particles are used in industry, we explored their inflammatory potential using mouse and cell models. BALB/c mice were exposed by inhalation for 2 h, 2 h on 4 consecutive days, or 2 h on 4 consecutive days for 4 weeks to several commercial TiO(2) nanoparticles, SiO(2) nanoparticles, and to nanosized TiO(2) generated in a gas-to-particle conversion process at 10 mg/m(3). In addition, effects of in vitro exposure of human macrophages and fibroblasts (MRC-9) to the different particles were assessed. SiO(2)-coated rutile TiO(2) nanoparticles (cnTiO(2)) was the only sample tested that elicited clear-cut pulmonary neutrophilia. Uncoated rutile and anatase as well as nanosized SiO(2) did not induce significant inflammation. Pulmonary neutrophilia was accompanied by increased expression of tumor necrosis factor-alpha (TNF-alpha) and neutrophil-attracting chemokine CXCL1 in the lung tissue. TiO(2) particles accumulated almost exclusively in the alveolar macrophages. In vitro exposure of murine and human macrophages to cnTiO(2) elicited significant induction of TNF-alpha and neutrophil-attracting chemokines. Stimulation of human fibroblasts with cnTiO(2)-activated macrophage supernatant induced high expression of neutrophil-attracting chemokines, CXCL1 and CXCL8. Interestingly, the level of lung inflammation could not be explained by the surface area of the particles, their primary or agglomerate particle size, or radical formation capacity but is rather explained by the surface coating. Our findings emphasize that it is vitally important to take into account in the risk assessment that alterations of nanoparticles, e.g., by surface coating, may drastically change their toxicological potential.