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Objective: In this study, we compared in vitro and in vivo bioactivity of nitrogen-doped multi-walled carbon nanotubes (NDMWCNT) to MWCNT to test the hypothesis that nitrogen doping would alter bioactivity. Materials and Methods: High-resolution transmission electron microscopy (TEM) confirmed the multilayer structure of MWCNT with an average layer distance of 0.36 nm, which was not altered by nitrogen doping: the nanomaterials had similar widths and lengths. In vitro studies with THP-1 cells and alveolar macrophages from C57BL/6 mice demonstrated that NDMWCNT were less cytotoxic and stimulated less IL-1β release compared to MWCNT. For in vivo studies, male C57BL/6J mice received a single dose of dispersion medium (DM), 2.5, 10 or 40 µg/mouse of NDMWCNT, or 40 µg/mouse of MWCNT by oropharyngeal aspiration. Animals were euthanized between 1 and 7 days post-exposure for whole lung lavage (WLL) studies. Results and Discussion: NDMWCNT caused time- and dose-dependent pulmonary inflammation. However, it was less than that caused by MWCNT. Activation of the NLRP3 inflammasome was assessed in particle-exposed mice by determining cytokine production in WLL fluid at 1 day post-exposure. Compared to DM-exposed mice, IL-1β and IL-18 were significantly increased in MWCNT- and NDMWCNT-exposed mice, but the increase caused by NDMWCNT was less than MWCNT. At 56 days post-exposure, histopathology determined lung fibrosis in MWCNT-exposed mice was greater than NDMWCNT-exposed mice. Conclusions: These data indicate nitrogen doping of MWCNT decreases their bioactivity, as reflected with lower in vitro and in vivo toxicity inflammation and lung disease. The lower activation of the NLRP3 inflammasome may be responsible. Abbreviations: NDMWCNT: nitrogen-doped multi-walled carbon nanotubes; MWCNT: multi-walled carbon nanotubes; TEM: transmission electron microscopy; HRTEM: high resolution transmission electron microscopy; IL-1ß: interleukin-1ß; DM: dispersion medium; WLL: whole lung lavage; IL-18: interleukin-18; GSD: geometric standard deviation; XPS: X-ray photoelectron spectroscopy; SEM: standard error of the mean; PMA: phorbol 12-myristate 13-acetate; LPS: lipopolysacharride; LDH: lactate dehydrogenase; AM: alveolar macrophage; PMN: polymorphonuclear leukocyte [ABSTRACT FROM AUTHOR] more...

Boron nitride nanotubes (BNNTs) are an emerging engineered nanomaterial attracting significant attention due to superior electrical, chemical and thermal properties. Currently, the toxicity profile of this material is largely unknown. Commercial grade BNNTs are composed of a mixture (BNNT-M) of ∼50–60% BNNTs, and ∼40–50% impurities of boron and hexagonal boron nitride. We performed acutein vitroandin vivostudies with commercial grade BNNT-M, dispersed by sonication in vehicle, in comparison to the extensively studied multiwalled carbon nanotube-7 (MWCNT-7). THP-1 wild-type and NLRP3-deficient human monocytic cells were exposed to 0–100 µg/ml and C57BL/6 J male mice were treated with 40 µg of BNNT-M forin vitroandin vivostudies, respectively.In vitro, BNNT-M induced a dose-dependent increase in cytotoxicity and oxidative stress. This was confirmedin vivofollowing acute exposure increase in bronchoalveolar lavage levels of lactate dehydrogenase, pulmonary polymorphonuclear cell influx, loss in mitochondrial membrane potential and augmented levels of 4-hydroxynonenal. Uptake of this material caused lysosomal destabilization, pyroptosis and inflammasome activation, corroborated by an increase in cathepsin B, caspase 1, increased protein levels of IL-1β and IL-18 bothin vitroandin vivo. Attenuation of these effects in NLRP3-deficient THP-1 cells confirmed NLRP3-dependent inflammasome activation by BNNT-M. BNNT-M induced a similar profile of inflammatory pulmonary protein production when compared to MWCNT-7. Functionally, pretreatment with BNNT-M caused suppression in bacterial uptake by THP-1 cells, an effect that was mirrored in challenged alveolar macrophages collected from exposed mice and attenuated with NLRP3 deficiency. Analysis of cytokines secreted by LPS-challenged alveolar macrophages collected afterin vivoexposure to dispersions of BNNT-M showed a differential macrophage response. The observed results demonstrated acute inflammation and toxicityin vitroandin vivofollowing exposure to sonicated BNNT-M was in part due to NLRP3 inflammasome activation. [ABSTRACT FROM PUBLISHER] more...

Printing devices are known to emit chemicals into the indoor atmosphere. Understanding factors that influence release of chemical contaminants from printers is necessary to develop effective exposure assessment and control strategies. In this study, a desktop fused deposition modeling (FDM) 3-dimensional (3-D) printer using acrylonitrile butadiene styrene (ABS) or polylactic acid (PLA) filaments and two monochrome laser printers were evaluated in a 0.5 m3chamber. During printing, chamber air was monitored for vapors using a real-time photoionization detector (results expressed as isobutylene equivalents) to measure total volatile organic compound (TVOC) concentrations, evacuated canisters to identify specific VOCs by off-line gas chromatography-mass spectrometry (GC-MS) analysis, and liquid bubblers to identify carbonyl compounds by GC-MS. Airborne particles were collected on filters for off-line analysis using scanning electron microscopy with an energy dispersive x-ray detector to identify elemental constituents. For 3-D printing, TVOC emission rates were influenced by a printer malfunction, filament type, and to a lesser extent, by filament color; however, rates were not influenced by the number of printer nozzles used or the manufacturer's provided cover. TVOC emission rates were significantly lower for the 3-D printer (49–3552 µg h−1) compared to the laser printers (5782–7735 µg h−1). A total of 14 VOCs were identified during 3-D printing that were not present during laser printing. 3-D printed objects continued to off-gas styrene, indicating potential for continued exposure after the print job is completed. Carbonyl reaction products were likely formed from emissions of the 3-D printer, including 4-oxopentanal. Ultrafine particles generated by the 3-D printer using ABS and a laser printer contained chromium. Consideration of the factors that influenced the release of chemical contaminants (including known and suspected asthmagens such as styrene and 4-oxopentanal) from a FDM 3-D printer should be made when designing exposure assessment and control strategies. [ABSTRACT FROM PUBLISHER] more...

The effects of acute pulmonary coexposures to silica and diesel particulate matter (DPM), which may occur in various mining operations, were investigatedin vivo. Rats were exposed by intratracheal instillation (IT) to silica (50 or 233 µg), DPM (7.89 or 50 µg) or silica and DPM combined in phosphate-buffered saline (PBS) or to PBS alone (control). At one day, one week, one month, two months and three months postexposure bronchoalveolar lavage and histopathology were performed to assess lung injury, inflammation and immune response. While higher doses of silica caused inflammation and injury at all time points, DPM exposure alone did not. DPM (50 µg) combined with silica (233 µg) increased inflammation at one week and one-month postexposure and caused an increase in the incidence of fibrosis at one month compared with exposure to silica alone. To assess susceptibility to lung infection following coexposure, rats were exposed by IT to 233 µg silica, 50 µg DPM, a combination of the two or PBS control one week before intratracheal inoculation with 5 × 105Listeria monocytogenes. At 1, 3, 5, 7 and 14 days following infection, pulmonary immune response and bacterial clearance from the lung were evaluated. Coexposure to DPM and silica did not alter bacterial clearance from the lung compared to control. Although DPM and silica coexposure did not alter pulmonary susceptibility to infection in this model, the study showed that noninflammatory doses of DPM had the capacity to increase silica-induced lung injury, inflammation and onset/incidence of fibrosis. [ABSTRACT FROM PUBLISHER] more...

Moisture-damaged indoor environments are thought to increase the toxicity of indoor air particulate matter (PM), indicating that a toxicological assay could be used as a method for recognizing buildings with indoor air problems. We aimed to test if our approach of analyzing the toxicity of actively collected indoor air PMin vitrodifferentiates moisture-damaged from non-damaged school buildings. We collected active air samples with NIOSH Bioaerosol Cyclone Samplers from moisture-damaged (index) and non-damaged (reference) school buildings (4 + 4). The teachers and pupils of the schools were administered a symptom questionnaire. Five samples of two size fractions [Stage 1 (>1.9 μm) and Stage 2 (1–1.9 μm)] were collected from each school. Mouse RAW264.7 macrophages were exposed to the collected PM for 24 h and subsequently analyzed for changes in cell metabolic activity, production of nitric oxide (NO), tumor necrosis factor (TNF)-α and interleukin (IL)-6. The teachers working in the moisture-damaged schools reported respiratory symptoms such as cough (p = 0.01) and shortness of breath (p = 0.01) more often than teachers from reference schools. Toxicity of the PM sample as such did not differentiate index from reference building,s but the toxicity adjusted for the amount of the particles tended to be higher in moisture-damaged schools. Further development of the method will require identification of other confounding factors in addition to the necessity to adjust for differences in particle counts between samples. [ABSTRACT FROM PUBLISHER] more...

An understanding of the mechanisms underlying diseases is critical for their prevention. Excessive exposure to crystalline silica is a risk factor for silicosis, a potentially fatal pulmonary disease. Male Fischer 344 rats were exposed by inhalation to crystalline silica (15 mg/m3, six hours/day, five days) and pulmonary response was determined at 44 weeks following termination of silica exposure. Additionally, global gene expression profiling in lungs and BAL cells and bioinformatic analysis of the gene expression data were done to understand the molecular mechanisms underlying the progression of pulmonary response to silica. A significant increase in lactate dehydrogenase activity and albumin content in BAL fluid (BALF) suggested silica-induced pulmonary toxicity in the rats. A significant increase in the number of alveolar macrophages and infiltrating neutrophils in the lungs and elevation in monocyte chemoattractant protein-1 (MCP-1) in BALF suggested the induction of pulmonary inflammation in the silica exposed rats. Histological changes in the lungs included granuloma formation, type II pneumocyte hyperplasia, thickening of alveolar septa and positive response to Masson’s trichrome stain. Microarray analysis of global gene expression detected 94 and 225 significantly differentially expressed genes in the lungs and BAL cells, respectively. Bioinformatic analysis of the gene expression data identified significant enrichment of several disease and biological function categories and canonical pathways related to pulmonary toxicity, especially inflammation. Taken together, these data suggested the involvement of chronic inflammation as a mechanism underlying the progression of pulmonary response to exposure of rats to crystalline silica at 44 weeks following termination of exposure. [ABSTRACT FROM PUBLISHER] more...

There is a need for toxicity tests capable of recognizing indoor environments with compromised air quality, especially in the context of moisture damage. One of the key issues is sampling, which should both provide meaningful material for analyses and fulfill requirements imposed by practitioners using toxicity tests for health risk assessment. We aimed to evaluate different existing methods of sampling indoor particulate matter (PM) to develop a suitable sampling strategy for a toxicological assay. During three sampling campaigns in moisture-damaged and non-damaged school buildings, we evaluated one passive and three active sampling methods: the Settled Dust Box (SDB), the Button Aerosol Sampler, the Harvard Impactor and the National Institute for Occupational Safety and Health (NIOSH) Bioaerosol Cyclone Sampler. Mouse RAW264.7 macrophages were exposed to particle suspensions and cell metabolic activity (CMA), production of nitric oxide (NO) and tumor necrosis factor (TNFα) were determined after 24 h of exposure. The repeatability of the toxicological analyses was very good for all tested sampler types. Variability within the schools was found to be high especially between different classrooms in the moisture-damaged school. Passively collected settled dust and PM collected actively with the NIOSH Sampler (Stage 1) caused a clear response in exposed cells. The results suggested the higher relative immunotoxicological activity of dust from the moisture-damaged school. The NIOSH Sampler is a promising candidate for the collection of size-fractionated PM to be used in toxicity testing. The applicability of such sampling strategy in grading moisture damage severity in buildings needs to be developed further in a larger cohort of buildings. [ABSTRACT FROM PUBLISHER] more...

Background: Although classified as metal oxides, cobalt monoxide (CoO) and lanthanum oxide (La2O3) nanoparticles, as representative transition and rare earth oxides, exhibit distinct material properties that may result in different hazardous potential in the lung. The current study was undertaken to compare the pulmonary effects of aerosolized whole body inhalation of these nanoparticles in mice. Results: Mice were exposed to filtered air (control) and 10 or 30 mg/m3 of each particle type for 4 days and then examined at 1 h, 1, 7 and 56 days post-exposure. The whole lung burden 1 h after the 4 day inhalation of CoO nanoparticles was 25 % of that for La2O3 nanoparticles. At 56 days post exposure, < 1 % of CoO nanoparticles remained in the lungs; however, 22–50 % of the La2O3 nanoparticles lung burden 1 h post exposure was retained at 56 days post exposure for low and high exposures. Significant accumulation of La2O3 nanoparticles in the tracheobronchial lymph nodes was noted at 56 days post exposure. When exposed to phagolysosomal simulated fluid, La nanoparticles formed urchin-shaped LaPO4 structures, suggesting that retention of this rare earth oxide nanoparticle may be due to complexation of cellular phosphates within lysosomes. CoO nanoparticles caused greater lactate dehydrogenase release in the bronchoalveolar fluid (BALF) compared to La2O3 nanoparticles at 1 day post exposure, while BAL cell differentials indicate that La2O3 nanoparticles generated more inflammatory cell infiltration at all doses and exposure points. Histopathological analysis showed acute inflammatory changes at 1 day after inhalation of either CoO or La2O3 nanoparticles. Only the 30 mg/m3 La2O3 nanoparticles exposure caused chronic inflammatory changes and minimal fibrosis at day 56 post exposure. This is in agreement with activation of the NRLP3 inflammasome after in vitro exposure of differentiated THP-1 macrophages to La2O3 but not after CoO nanoparticles exposure. Conclusion: Taken together, the inhalation studies confirmed the trend of our previous sub-acute aspiration study, which reported that CoO nanoparticles induced more acute pulmonary toxicity, while La2O3 nanoparticles caused chronic inflammatory changes and minimal fibrosis. [ABSTRACT FROM AUTHOR] more...

Direct-reading instruments have been widely used for characterizing airborne nanoparticles in inhalation toxicology and industrial hygiene studies for exposure/risk assessments. Instruments using electrical mobility sizing followed by optical counting, e.g., scanning or sequential mobility particle spectrometers (SMPS), have been considered as the "gold standard" for characterizing nanoparticles. An SMPS has the advantage of rapid response and has been widely used, but there is little information on its performance in assessing the full spectrum of nanoparticles encountered in the workplace. In this study, an SMPS was evaluated for its effectiveness in producing "monodisperse" aerosol and its adequacy in characterizing overall particle size distribution using three test aerosols, each mimicking a unique class of real-life nanoparticles: singlets of nearly spherical titanium dioxide (TiO2), agglomerates of fiber-like multi-walled carbon nanotube (MWCNT),and aggregates that constitutes welding fume (WF). These aerosols were analyzed by SMPS, cascade impactor, and by counting and sizing of discrete particles by scanning and transmission electron microscopy. The effectiveness of the SMPS to produce classified particles (fixed voltage mode) was assessed by examination of the resulting geometric standard deviation (GSD) from the impactor measurement. Results indicated that SMPS performed reasonably well for TiO2 (GSD = 1.3), but not for MWCNT and WF as evidenced by the large GSD values of 1.8 and 1.5, respectively. For overall characterization, results from SMPS (scanning voltage mode) exhibited particle-dependent discrepancies in the size distribution and total number concentration compared to those from microscopic analysis. Further investigation showed that use of a single-stage impactor at the SMPS inlet could distort the size distribution and underestimate the concentration as shown by the SMPS, whereas the presence of vapor molecules or atom clusters in some test aerosols might cause artifacts by counting "phantom particles." Overall, the information obtained from this study will help understand the limitations of the SMPS in measuring nanoparticles so that one can adequately interpret the results for risk assessments and exposure prevention in an occupational or ambient environment. [ABSTRACT FROM AUTHOR] more...

Desktop three-dimensional (3D) printers are becoming commonplace in business offices, public libraries, university labs and classrooms, and even private homes; however, these settings are generally not designed for exposure control. Prior experience with a variety of office equipment devices such as laser printers that emit ultrafine particles (UFP) suggests the need to characterize 3D printer emissions to enable reliable risk assessment. The aim of this study was to examine factors that influence particulate emissions from 3D printers and characterize their physical properties to inform risk assessment. Emissions were evaluated in a 0.5-m3chamber and in a small room (32.7 m3) using real-time instrumentation to measure particle number, size distribution, mass, and surface area. Factors evaluated included filament composition and color, as well as the manufacturer-provided printer emissions control technologies while printing an object. Filament type significantly influenced emissions, with acrylonitrile butadiene styrene (ABS) emitting larger particles than polylactic acid (PLA), which may have been the result of agglomeration. Geometric mean particle sizes and total particle (TP) number and mass emissions differed significantly among colors of a given filament type. Use of a cover on the printer reduced TP emissions by a factor of 2. Lung deposition calculations indicated a threefold higher PLA particle deposition in alveoli compared to ABS. Desktop 3D printers emit high levels of UFP, which are released into indoor environments where adequate ventilation may not be present to control emissions. Emissions in nonindustrial settings need to be reduced through the use of a hierarchy of controls, beginning with device design, followed by engineering controls (ventilation) and administrative controls such as choice of filament composition and color. [ABSTRACT FROM AUTHOR] more...

Nine gas metal arc welding (GMAW) processes for stainless steel were assessed for fume generation rates, fume generation rates per g of electrode consumed, and emission rates for hexavalent chromium (Cr6+). Elemental manganese, nickel, chromium, iron emissions per unit length of weld, and labor plus consumables costs were similarly measured. Flux-cored arc welding and shielded metal arc (SMAW) processes were also studied. The objective was to identify the best welding processes for reducing workplace exposures, and estimate costs for all processes. Using a conical chamber, fumes were collected, weighed, recovered, and analyzed by inductively coupled atomic emission spectroscopy for metals, and by ion chromatography for Cr6+. GMAW processes used were Surface Tension Transfer, Regulated Metal Deposition, Cold Metal Transfer, short-circuit, axial spray, and pulsed spray modes. Flux-cored welding used gas shielding; SMAW used E308 rods. Costs were estimated as dollars per m length of a ¼ in (6.3 mm) thick horizontal butt weld; equipment costs were estimated as ratios of new equipment costs to a 250 ampere capacity SMAW welding machine. Results indicate a broad range of fume emission factors for the processes studied. Fume emission rates per g of electrode were lowest for GMAW processes such as pulsed-spray mode (0.2 mg/g), and highest for SMAW (8 mg fume/g electrode). Emission rates of Cr6+ ranged from 50–7800 µg/min, and Cr6+ generation rates per g electrode ranged from 1–270 µg/g. Elemental Cr generation rates spanned 13–330 µg/g. Manganese emission rates ranged from 50–300 µg/g. Nickel emission rates ranged from 4–140 µg/g. Labor and consumables costs ranged from $3.15 (GMAW pulsed spray) to $7.40 (SMAW) per meter of finished weld, and were measured or estimated for all 11 processes tested. Equipment costs for some processes may be as much as five times the cost of a typical SMAW welding machine. The results show that all of the GMAW processes in this study can substantially reduce fume, Cr6+, manganese and costs relative to SMAW, the most commonly used welding process, and several have exceptional capabilities for reducing emissions. [ABSTRACT FROM AUTHOR] more...

Inhalation exposure to multi-walled carbon nanotubes (MWCNT) in mice results in inflammation, fibrosis and the promotion of lung adenocarcinoma; however, the molecular basis behind these pathologies is unknown. This study determined global mRNA and miRNA profiles in whole blood from mice exposed by inhalation to MWCNT that correlated with the presence of lung hyperplasia, fibrosis, and bronchiolo-alveolar adenoma and adenocarcinoma. Six-week-old, male, B6C3F1 mice received a single intraperitoneal injection of either the DNA-damaging agent methylcholanthrene (MCA, 10 µg g-1 body weight) or vehicle (corn oil). One week after injections, mice were exposed by inhalation to MWCNT (5mgm-3, 5 hours per day, 5 days per week) or filtered air (control) for a total of 15days. At 17months post-exposure, mice were euthanized and examined for the development of pathological changes in the lung, and whole blood was collected and analyzed using microarray analysis for global mRNA and miRNA expression. Numerous mRNAs and miRNAs in the blood were significantly up- or down-regulated in animals developing pathological changes in the lung after MCA/corn oil administration followed by MWCNT/air inhalation, including fcrl5 and miR-122-5p in the presence of hyperplasia, mthfd2 and miR-206-3p in the presence of fibrosis, fam178a and miR-130a-3p in the presence of bronchiolo-alveolar adenoma, and il7r and miR-210-3p in the presence of bronchiolo-alveolar adenocarcinoma, among others. The changes in miRNA and mRNA expression, and their respective regulatory networks, identified in this study may potentially serve as blood biomarkers for MWCNT-induced lung pathological changes. [ABSTRACT FROM AUTHOR] more...

Ambient bioaerosols are ubiquitous in the daily environment and can affect health in various ways. However, few studies have been conducted to comprehensively evaluate personal bioaerosol exposure in occupational and indoor environments because of the complex composition of bioaerosols and the lack of standardized sampling/analysis methods. We conducted a study to determine the most efficient collection/analysis method for the personal exposure assessment of multiple bioaerosols. The sampling efficiencies of three filters and four samplers were compared. According to our results, polycarbonate (PC) filters had the highest relative efficiency, particularly for bacteria. Side-by-side sampling was conducted to evaluate the three filter samplers (with PC filters) and the NIOSH Personal Bioaerosol Cyclone Sampler. According to the results, the Button Aerosol Sampler and the IOM Inhalable Dust Sampler had the highest relative efficiencies for fungi and bacteria, followed by the NIOSH sampler. Personal sampling was performed in a pig farm to assess occupational bioaerosol exposure and to evaluate the sampling/analysis methods. The Button and IOM samplers yielded a similar performance for personal bioaerosol sampling at the pig farm. However, the Button sampler is more likely to be clogged at high airborne dust concentrations because of its higher flow rate (4 L/min). Therefore, the IOM sampler is a more appropriate choice for performing personal sampling in environments with high dust levels. In summary, the Button and IOM samplers with PC filters are efficient sampling/analysis methods for the personal exposure assessment of multiple bioaerosols. [ABSTRACT FROM AUTHOR] more...

A laboratory study was conducted to determine the mass of total Cr, Cr(VI), Mn, and Ni in 15 size fractions for mild and stainless steel gas-metal arc welding (GMAW) fumes. Samples were collected using a nano multi orifice uniform deposition impactor (MOUDI) with polyvinyl chloride filters on each stage. The filters were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography. Limits of detection (LODs) and quantitation (LOQs) were experimentally calculated and percent recoveries were measured from spiked metals in solution and dry, certified welding-fume reference material. The fraction of Cr(VI) in total Cr was estimated by calculating the ratio of Cr(VI) to total Cr mass for each particle size range. Expected, regional deposition of each metal was estimated according to respiratory-deposition models. The weight percent (standard deviation) of Mn in mild steel fumes was 9.2% (6.8%). For stainless steel fumes, the weight percentages were 8.4% (5.4%) for total Cr, 12.2% (6.5%) for Mn, 2.1% (1.5%) for Ni and 0.5% (0.4%) for Cr(VI). All metals presented a fraction between 0.04 and 0.6 μm. Total Cr and Ni presented an additional fraction <0.03 μm. On average 6% of the Cr was found in the Cr(VI) valence state. There was no statistical difference between the smallest and largest mean Cr(VI) to total Cr mass ratio (p-value = 0.19), hence our analysis does not show that particle size affects the contribution of Cr(VI) to total Cr. The predicted total respiratory deposition for the metal particles was ∼25%. The sites of principal deposition were the head airways (7–10%) and the alveolar region (11–14%). Estimated Cr(VI) deposition was highest in the alveolar region (14%). [ABSTRACT FROM AUTHOR] more...

Limited information exists regarding the health risks associated with inhaling aerosols that are generated during resistance spot welding of metals treated with adhesives. Toxicology studies evaluating spot welding aerosols are non-existent. A resistance spot welding aerosol generator and inhalation exposure system was developed. The system was designed by directing strips of sheet metal that were treated with an adhesive to two electrodes of a spot welder. Spot welds were made at a specified distance from each other by a computer-controlled welding gun in a fume collection chamber. Different target aerosol concentrations were maintained within the exposure chamber during a 4-h exposure period. In addition, the exposure system was run in two modes, spark and no spark, which resulted in different chemical profiles and particle size distributions. Complex aerosols were produced that contained both metal particulates and volatile organic compounds (VOCs). Size distribution of the particles was multi-modal. The majority of particles were chain-like agglomerates of ultrafine primary particles. The submicron mode of agglomerated particles accounted for the largest portion of particles in terms of particle number. Metal expulsion during spot welding caused the formation of larger, more spherical particles (spatter). These spatter particles appeared in the micron size mode and accounted for the greatest amount of particles in terms of mass. With this system, it is possible to examine potential mechanisms by which spot welding aerosols can affect health, as well as assess which component of the aerosol may be responsible for adverse health outcomes. [ABSTRACT FROM AUTHOR] more...

Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland fire fighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 μm and a fine particle mode with a mass median aerodynamic diameter < 0.5 μm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p < 0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are available for this article. Go to the publisher's online edition ofJournal of Occupational and Environmental Hygienefor the following free supplemental resources: a file containing additional information on historical studies of wildland fire exposures, a file containing the daily-exposure-severity questionnaire completed by wildland firefighter participants at the end of each day, and a file containing additional details of the investigation of correlations between carbon monoxide concentrations and other measured exposure factors in the current study.] [ABSTRACT FROM PUBLISHER] more...

To provide quantitative information to choose the best welding processes for minimizing workplace emissions, nine gas metal arc welding (GMAW) processes for mild steel were assessed for fume generation rates, normalized fume generation rates (milligram fume per gram of electrode consumed), and normalized generation rates for elemental manganese, nickel, and iron. Shielded metal arc welding (SMAW) and flux-cored arc-welding (FCAW) processes were also profiled. The fumes were collected quantitatively in an American Welding Society-type fume chamber and weighed, recovered, homogenized, and analyzed by inductively coupled atomic emission spectroscopy for total metals. The processes included GMAW with short circuit, globular transfer, axial spray, pulsed spray, Surface Tension Transfer™, Regulated Metal Deposition™, and Cold Metal Transfer™ (CMT) modes. Flux-cored welding was gas shielded, and SMAW was a single rod type. Results indicate a wide range of fume emission factors for the process variations studied. Fume emission rates per gram of electrode consumed were highest for SMAW (~13mg fume g−1 electrode) and lowest for GMAW processes such as pulsed spray (~1.5mg g−1) and CMT (~1mg g−1). Manganese emission rates per gram of electrode consumed ranged from 0.45mg g−1 (SMAW) to 0.08mg g−1 (CMT). Nickel emission rates were generally low and ranged from ~0.09 (GMAW short circuit) to 0.004mg g−1 (CMT). Iron emission rates ranged from 3.7 (spray-mode GMAW) to 0.49mg g−1 (CMT). The processes studied have significantly different costs, and cost factors are presented based on a case study to allow comparisons between processes in specific cost categories. Costs per linear meter of weld were $31.07 (SMAW), $12.37 (GMAW short circuit), and $10.89 (FCAW). Although no single process is the best for minimizing fume emissions and costs while satisfying the weld requirements, there are several processes that can minimize emissions. This study provides information to aid in those choices. Suggestions for overcoming barriers to utilizing new and less hazardous welding processes are also discussed. [ABSTRACT FROM AUTHOR] more...

Background Engineered carbon nanotubes are currently used in many consumer and industrial products such as paints, sunscreens, cosmetics, toiletries, electronic processes and industrial lubricants. Carbon nanotubes are among the more widely used nanoparticles and come in two major commercial forms, single-walled carbon nanotubes (SWCNT) and the more rigid, multiwalled carbon nanotubes (MWCNT). The low density and small size of these particles makes respiratory exposures likely. Many of the potential health hazards have not been investigated, including their potential for carcinogenicity. We, therefore, utilized a two stage initiation/promotion protocol to determine whether inhaled MWCNT act as a complete carcinogen and/or promote the growth of cells with existing DNA damage. Six week old, male, B6C3F1 mice received a single intraperitoneal (ip) injection of either the initiator methylcholanthrene(MCA, 10 μg/g BW, i.p.), or vehicle (corn oil). One week after i.p. injections, mice were exposed by inhalation to MWCNT (5 mg/m3, 5 hours/day, 5 days/week) or filtered air (controls) for a total of 15 days. At 17 months post-exposure, mice were euthanized and examined for lung tumor formation. Results Twenty-three percent of the filtered air controls, 26.5% of the MWCNT-exposed, and 51.9% of the MCA-exposed mice, had lung bronchiolo-alveolar adenomas and lung adenocarcinomas. The average number of tumors per mouse was 0.25, 0.81 and 0.38 respectively. By contrast, 90.5% of the mice which received MCA followed by MWCNT had bronchiolo-alveolar adenomas and adenocarcinomas with an average of 2.9 tumors per mouse 17months after exposure. Indeed, 62% of the mice exposed to MCA followed by MWCNT had bronchiolo-alveolar adenocarcinomas compared to 13% of the mice that received filtered air, 22% of the MCA-exposed, or 14% of the MWCNT-exposed. Mice with early morbidity resulting in euthanasia had the highest rate of metastatic disease. Three mice exposed to both MCA and MWCNT that were euthanized early had lung adenocarcinoma with evidence of metastasis (5.5%). Five mice (9%) exposed to MCA and MWCNT and 1 (1.6%) exposed to MCA developed serosal tumors morphologically consistent with sarcomatous mesotheliomas, whereas mice administered MWCNT or air alone did not develop similar neoplasms. Conclusions These data demonstrate that some MWCNT exposures promote the growth and neoplastic progression of initiated lung cells in B6C3F1 mice. In this study, the mouse MWCNT lung burden of 31.2 μg/mouse approximates feasible human occupational exposures. Therefore, the results of this study indicate that caution should be used to limit human exposures to MWCNT. [ABSTRACT FROM AUTHOR] more...

This study investigated the in vivo pulmonary toxicity of inhaled multi-walled carbon nanotubes (MWCNT). Mice-inhaled aerosolized MWCNT (10 mg/m3, 5 h/day) for 2, 4, 8 or 12 days. MWCNT lung burden was linearly related to exposure duration. MWCNT-induced pulmonary inflammation was assessed by determining whole lung lavage (WLL) polymorphonuclear leukocytes (PMN). Lung cytotoxicity was assessed by WLL fluid LDH activities. WLL fluid albumin concentrations were determined as a marker of alveolar air-blood barrier integrity. These parameters significantly increased in MWCNT-exposed mice versus controls and were dose-dependent. Histopathologic alterations identified in the lung included (1) bronciolocentric inflammation, (2) bronchiolar epithelial hyperplasia and hypertrophy, (3) fibrosis, (4) vascular changes and (5) rare pleural penetration. MWCNT translocated to the lymph node where the deep paracortex was expanded after 8 or 12 days. Acute inhalation of MWCNT induced dose-dependent pulmonary inflammation and damage with rapid development of pulmonary fibrosis, and also demonstrated that MWCNT can reach the pleura after inhalation exposure. [ABSTRACT FROM AUTHOR] more...

Humans will again set foot on the moon. The moon is covered by a layer of fine dust, which can pose a respiratory hazard. We investigated the pulmonary toxicity of lunar dust in rats exposed to 0, 2.1, 6.8, 20.8 and 60.6 mg/m3 of respirable-size lunar dust for 4 weeks (6 h/day, 5 days/week); the aerosols in the nose-only exposure chambers were generated from a jet-mill ground preparation of a lunar soil collected during the Apollo 14 mission. After 4 weeks of exposure to air or lunar dust, groups of five rats were euthanized 1 day, 1 week, 4 weeks or 13 weeks after the last exposure for assessment of pulmonary toxicity. Biomarkers of toxicity assessed in bronchoalveolar fluids showed concentration-dependent changes; biomarkers that showed treatment effects were total cell and neutrophil counts, total protein concentrations and cellular enzymes (lactate dehydrogenase, glutamyl transferase and aspartate transaminase). No statistically significant differences in these biomarkers were detected between rats exposed to air and those exposed to the two low concentrations of lunar dust. Dose-dependent histopathology, including inflammation, septal thickening, fibrosis and granulomas, in the lung was observed at the two higher exposure concentrations. No lesions were detected in rats exposed to ≤6.8 mg/m3. This 4-week exposure study in rats showed that 6.8 mg/m3 was the highest no-observable-adverse-effect level (NOAEL). These results will be useful for assessing the health risk to humans of exposure to lunar dust, establishing human exposure limits and guiding the design of dust mitigation systems in lunar landers or habitats. [ABSTRACT FROM AUTHOR] more...

ABSTRACT Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with exposure to silica. Rats were exposed to crystalline silica by inhalation (15 mg m−3, 6 h per day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8 and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5-fold change and <0.01 false discovery rate P-value) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats. Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The number of biological functions, canonical pathways and molecular networks significantly affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes detected during the post-exposure time intervals, also exhibited a steady increase similar to the silica-induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved inflammation was the single most significant biological response to pulmonary exposure to silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a potential novel mechanism for silica-induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat. Published 2012. This article is a US Government work and is in the public domain in the USA. [ABSTRACT FROM AUTHOR] more...

Nanotechnology involves technology, science, and engineering in dimensions less than 100 nm. A virtually infinite number of potential nanoscale products can be produced from many different molecules and their combinations. The exponentially increasing number of nanoscale products will solve critical needs in engineering, science, and medicine. However, the virtually infinite number of potential nanotechnology products is a challenge for toxicologic pathologists. Because of their size, nanoparticulates can have therapeutic and toxic effects distinct from micron-sized particulates of the same composition. In the nanoscale, distinct intercellular and intracellular translocation pathways may provide a different distribution than that obtained by micron-sized particulates. Nanoparticulates interact with subcellular structures including microtubules, actin filaments, centrosomes, and chromatin; interactions that may be facilitated in the nanoscale. Features that distinguish nanoparticulates from fine particulates include increased surface area per unit mass and quantum effects. In addition, some nanotechnology products, including the fullerenes, have a novel and reactive surface. Augmented microscopic procedures including enhanced dark-field imaging, immunofluorescence, field-emission scanning electron microscopy, transmission electron microscopy, and confocal microscopy are useful when evaluating nanoparticulate toxicologic pathology. Thus, the pathology assessment is facilitated by understanding the unique features at the nanoscale and the tools that can assist in evaluating nanotoxicology studies. [ABSTRACT FROM PUBLISHER] more...

The widespread increase in the production and use of nanomaterials has increased the potential for nanoparticle exposure; however, the biological effects of nanoparticle inhalation are poorly understood. Rats were exposed to nanosized titanium dioxide aerosols (10 μg lung burden); at 24 h post-exposure, the spinotrapezius muscle was prepared for intravital microscopy. Nanoparticle exposure did not alter perivascular nerve stimulation (PVNS)-induced arteriolar constriction under normal conditions; however, adrenergic receptor inhibition revealed a more robust effect. Nanoparticle inhalation reduced arteriolar dilation in response to active hyperaemia (AH). In both PVNS and AH experiments, nitric oxide synthase (NOS) inhibition affected only controls. Whereas cyclooxygenase (COX) inhibition only attenuated AH-induced arteriolar dilation in nanoparticle-exposed animals. This group displayed an enhanced U46619 constriction and attenuated iloprost-induced dilation. Collectively, these studies indicate that nanoparticle exposure reduces microvascular NO bioavailability and alters COX-mediated vasoreactivity. Furthermore, the enhanced adrenergic receptor sensitivity suggests an augmented sympathetic responsiveness. [ABSTRACT FROM AUTHOR] more...

Engineered nanomaterials have been developed for widespread applications due to many highly unique and desirable characteristics. The purpose of this study was to assess pulmonary inflammation and subepicardial arteriolar reactivity in response to multi-walled carbon nanotube (MWCNT) inhalation and evaluate the time course of vascular alterations. Rats were exposed to MWCNT aerosols producing pulmonary deposition. Pulmonary inflammation via bronchoalveolar lavage and MWCNT translocation from the lungs to systemic organs was evident 24 h post-inhalation. Coronary arterioles were evaluated 24-168 h post-exposure to determine microvascular response to changes in transmural pressure, endothelium-dependent and -independent reactivity. Myogenic responsiveness, vascular smooth muscle reactivity to nitric oxide, and a-adrenergic responses all remained intact. However, a severe impact on endothelium-dependent dilation was observed within 24 h after MWCNT inhalation, a condition which improved, but did not fully return to control after 168 h. In conclusion, results indicate that MWCNT inhalation not only leads to pulmonary inflammation and cytotoxicity at low lung burdens, but also a low level of particle translocation to systemic organs. MWCNT inhalation also leads to impairments of endothelium-dependent dilation in the coronary microcirculation within 24 h, a condition which does not fully dissipate within 168 h. The innovations within the field of nanotechnology, while exciting and novel, can only reach their full potential if toxicity is first properly assessed. [ABSTRACT FROM AUTHOR] more...

This study intends to develop protocols for sampling and characterizing multi-walled carbon nanotube (MWCNT) aerosols in workplaces or during inhalation studies. Manufactured dry powder containing MWCNT's, combined with soot and metal catalysts, form complex morphologies and diverse shapes. The aerosols, examined in this study, were produced using an acoustical generator. Representative samples were collected from an exposure chamber using filters and a cascade impactor for microscopic and gravimetric analyses. Results from filters showed that a density of 0.008-0.10 particles per µm2 filter surface provided adequate samples for particle counting and sizing. Microscopic counting indicated that MWCNT's, resuspended at a concentration of 10 mg/m3, contained 2.7 × 104 particles/cm3. Each particle structure contained an average of 18 nanotubes, resulting in a total of 4.9 × 105 nanotubes/cm3. In addition, fibrous particles within the aerosol had a count median length of 3.04 µm and a width of 100.3 nm, while the isometric particles had a count median diameter of 0.90 µm. A combination of impactor and microscopic measurements established that the mass median aerodynamic diameter of the mixture was 1.5 µm. It was also determined that the mean effective density of well-defined isometric particles was between 0.71 and 0.88 g/cm3, and the mean shape factor of individual nanotubes was between 1.94 and 2.71. The information obtained from this study can be used for designing animal inhalation exposure studies and adopted as guidance for sampling and characterizing MWCNT aerosols in workplaces. The measurement scheme should be relevant for any carbon nanotube aerosol. [ABSTRACT FROM AUTHOR] more...

The need to determine occupational exposure to bioaerosols has notably increased in the past decade, especially for microbiology-related workplaces and laboratories. Recently, two new cyclone-based personal bioaerosol samplers were developed by the National Institute for Occupational Safety and Health (NIOSH) in the USA and the Research Center for Toxicology and Hygienic Regulation of Biopreparations (RCT & HRB) in Russia to monitor bioaerosol exposure in the workplace. Here, a series of wind tunnel experiments were carried out to evaluate the physical sampling performance of these two samplers in moving air conditions, which could provide information for personal biological monitoring in a moving air environment. The experiments were conducted in a small wind tunnel facility using three wind speeds (0.5, 1.0 and 2.0 m s−1) and three sampling orientations (0°, 90°, and 180°) with respect to the wind direction. Monodispersed particles ranging from 0.5 to 10 μm were employed as the test aerosols. The evaluation of the physical sampling performance was focused on the aspiration efficiency and capture efficiency of the two samplers. The test results showed that the orientation-averaged aspiration efficiencies of the two samplers closely agreed with the American Conference of Governmental Industrial Hygienists (ACGIH) inhalable convention within the particle sizes used in the evaluation tests, and the effect of the wind speed on the aspiration efficiency was found negligible. The capture efficiencies of these two samplers ranged from 70% to 80%. These data offer important information on the insight into the physical sampling characteristics of the two test samplers. [ABSTRACT FROM AUTHOR] more...

Minimally invasive approaches to detect/predict target organ toxicity have significant practical applications in occupational toxicology. The potential application of peripheral blood transcriptomics as a practical approach to study the mechanisms of silica-induced pulmonary toxicity was investigated. Rats were exposed by inhalation to crystalline silica (15 mg/m3, 6 h/day, 5 days) and pulmonary toxicity and global gene expression profiles of lungs and peripheral blood were determined at 32 weeks following termination of exposure. A significant elevation in bronchoalveolar lavage fluid lactate dehydrogenase activity and moderate histological changes in the lungs, including type II pneumocyte hyperplasia and fibrosis, indicated pulmonary toxicity in the rats. Similarly, significant infiltration of neutrophils and elevated monocyte chemotactic protein-1 levels in the lungs showed pulmonary inflammation in the rats. Microarray analysis of global gene expression profiles identified significant differential expression [>1.5-fold change and false discovery rate (FDR) p < 0.01] of 520 and 537 genes, respectively, in the lungs and blood of the exposed rats. Bioinformatics analysis of the differentially expressed genes demonstrated significant similarity in the biological processes, molecular networks, and canonical pathways enriched by silica exposure in the lungs and blood of the rats. Several genes involved in functions relevant to silica-induced pulmonary toxicity such as inflammation, respiratory diseases, cancer, cellular movement, fibrosis, etc, were found significantly differentially expressed in the lungs and blood of the silica-exposed rats. The results of this study suggested the potential application of peripheral blood gene expression profiling as a toxicologically relevant and minimally invasive surrogate approach to study the mechanisms underlying silica-induced pulmonary toxicity. [ABSTRACT FROM AUTHOR] more...

Background: Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc -- stainless steel (GMA-SS) welding fume at 40 mg/m3 for 3 hr/d for 10 d and sacrificed 4 hr, 14 d and 28 d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. Results: The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28 d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10). In addition, pulmonary expression of interferon α and β and Irf7 specific pattern recognition receptors (PRR) and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3) were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88) to inhalation of GMA-SS. Conclusion: This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure. [ABSTRACT FROM AUTHOR] more...

Measurement of the surface area of airborne nanoparticles as administered to an experimental subject is critical for characterizing exposures during inhalation experiments. A filter-based surface area measurement methodology is described herein that allows for such determinations. Krypton gas adsorption was used to determine total particle surface area. Track-etched polycarbonate 0.4 μm pore filters were chosen as the collection substrate for metal oxide particles due to their highly reproducible surface areas and low background weights. The subject nanomaterials included two different batches of ultrafine TiO2, TiO2 nanorods, and SiO2. The instrument detection limit for surface area was 200 cm2 (0.02 m2). Ninety percent confidence interval estimates of method accuracy were 17.7-23.5% with a point estimate of 20.8%. The filter-based surface area measurement strategy is demonstrated to be a viable sampling and analysis methodology that provides much needed physical characterization information of particles as administered in an animal inhalation chamber. [ABSTRACT FROM AUTHOR] more...

The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m3 (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile. [ABSTRACT FROM AUTHOR] more...

Fine- and coarse-sized titanium dioxide (TiO2) particles are considered to be relatively inert when inhaled. The goal of this study was to assess potential lung toxicity associated with well-characterized, non-dispersed rutile TiO2 nanorods (10 × 40 nm). In vitro bioreactivity of TiO2 nanorods was determined by electron spin resonance (ESR) to measure free radical production. To assess pulmonary effects in vivo, Sprague-Dawley rats were intratracheally instilled with saline, silica, or TiO2 nanorods (10 μg, 100 μg, or 1 mg/rat). On d 1, 3, and 6 posttreatment, left lungs were preserved for microscopy and histopathology, and lung lavage was performed on right lungs. Additional rats were treated with saline or TiO2 nanorods (100 μg or 1 mg/rat) on d 0, intratracheally inoculated with 5 × 105 Listeria monocytogenes on d 3, and bacterial clearance was assessed. ESR showed a significant concentration-dependent generation of hydroxyl radicals by TiO2 nanorods in the presence and absence of macrophages; however, the hydroxyl radical signals from TiO2 samples were low compared to silica. Rats exposed to 1 mg of TiO2 nanorods had significantly elevated levels of lung injury, inflammation, and lavage fluid monocyte chemoattractant protein (MCP)-1 and macrophage inflammatory protein (MIP)-2 on d 1 and 3 that subsided by d 6, unlike the silica response that persisted. Immune cytokine secretion in the lung and bacterial clearance were not affected by preexposure to TiO2 nanorods. To summarize, non-dispersed TiO2 nanorods were found to induce radical formation and cellular oxidant production, and to generate transient and reversible pneumotoxic effects, and to not markedly alter pulmonary immune function. [ABSTRACT FROM AUTHOR] more...

Welding generates complex metal fumes that vary in composition. The objectives of this study were to compare the persistence of deposited metals and the inflammatory potential of stainless and mild steel welding fumes, the two most common fumes used in US industry. Sprague-Dawley rats were exposed to 40 mg/m of stainless or mild steel welding fumes for 3 h/day for 3 days. Controls were exposed to filtered air. Generated fume was collected, and particle size and elemental composition were determined. Bronchoalveolar lavage was done on days 0, 8, 21, and 42 after the last exposure to assess lung injury/inflammation and to recover lung phagocytes. Non-lavaged lung samples were analyzed for total and specific metal content as a measure of metal persistence. Both welding fumes were similar in particle morphology and size. Following was the chemical composition of the fumes-stainless steel: 57% Fe, 20% Cr, 14% Mn, and 9% Ni; mild steel: 83% Fe and 15% Mn. There was no effect of the mild steel fume on lung injury/inflammation at any time point compared to air control. Lung injury and inflammation were significantly elevated at 8 and 21 days after exposure to the stainless steel fume compared to control. Stainless steel fume exposure was associated with greater recovery of welding fume-laden macrophages from the lungs at all time points compared with the mild steel fume. A higher concentration of total metal was observed in the lungs of the stainless steel welding fume at all time points compared with the mild steel fume. The specific metals present in the two fumes were cleared from the lungs at different rates. The potentially more toxic metals (e.g., Mn, Cr) present in the stainless steel fume were cleared from the lungs more quickly than Fe, likely increasing their translocation from the respiratory system to other organs. [ABSTRACT FROM AUTHOR] more...

Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) welding fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS welding fume at 40 mg/m3 ×× 3 h/day for 6 and 10 days. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-αα (TNF-αα) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice. [ABSTRACT FROM AUTHOR] more...

This is the first report demonstrating that a commercially available household consumer product produces nanoparticles in a respirable range. This report describes a method developed to characterize nanoparticles that were produced under typical exposure conditions when using a consumer spray product. A well-controlled indoor environment was simulated for conducting spray applications approximating a human exposure scenario. Results indicated that, while aerosol droplets were large with a count median diameter of 22 µm during spraying, the final aerosol contained primarily solid TiO2 particles with a diameter of 75 nm. This size reduction was due to the surface deposition of the droplets and the rapid evaporation of the aerosol propellant. In the breathing zone, the aerosol, containing primarily individual particles (>90%), had a mass concentration of 3.4 mg/m3, or 1.6 × 105 particles/cm3, with a nanoparticle fraction limited to 170 µg/m3, or 1.2 × 105 particles/cm3. The results were used to estimate the pulmonary dose in an average human (0.075 µg TiO2 per m2 alveolar epithelium per minute) and rat (0.03 µg TiO2) and, consequently, this information was used to design an inhalation exposure system. The system consisted of a computer-controlled solenoid ''finger'' for generating constant concentrations of spray can aerosols inside a chamber. Test results demonstrated great similarity between the solenoid ''finger''-dispersed aerosol compared to human-generated aerosol. Future investigations will include an inhalation study to obtain information on dose-response relationships in rats and to use it to establish a No Effect Exposure Level for setting guidelines for this consumer product. [ABSTRACT FROM AUTHOR] more...

Exposure to ambient nanoparticles (defined as particulate matter [PM] having one dimension <100 nm) is associated with increased risk of childhood and adult asthma. Nanomaterials feature a smaller aerodynamic diameter and a higher surface area per unit mass ratio compared to fine or coarse-sized particles, resulting in greater lung deposition efficiency and an increased potential for biological interaction. The neurotrophins nerve growth factor and brain-derived neurotrophic factor are key regulatory elements of neuronal development and responsiveness of airway sensory neurons. Changes in their expression are associated with bronchoconstriction, airway hyperresponsiveness, and airway inflammation. The neurogenic-mediated control of airway responses is a key pathophysiological mechanism of childhood asthma. However, the effects of nanoparticle exposure on neurotrophin-driven airway responses and their potential role as a predisposing factor for developing asthma have not been clearly elucidated. In this study, in vivo inhalation exposure to titanium dioxide nanoparticles (12 mg/m3; 5.6 h/d for 3 d) produced upregulation of lung neurotrophins in weanling (2-wk-old) and newborn (2-d-old) rats but not in adult (12-wk-old) animals compared to controls. This effect was associated with increased airway responsiveness and upregulation of growth-related oncogene/keratine-derived chemokine (GRO/KC; CXCL1, rat equivalent of human interleukin [IL]-8) in bronchoalveolar lavage fluid. These data show for the first time that exposure to nanoparticulate upregulates the expression of lung neurotrophins in an age-dependent fashion and that this effect is associated with airway hyperresponsiveness and inflammation. These results suggest the presence of a critical window of vulnerability in earlier stages of lung development, which may lead to a higher risk of developing asthma. [ABSTRACT FROM AUTHOR] more...

Background. Considerable controversy exists with regard to whether influenza virus and respiratory syncytial virus (RSV) are spread by the inhalation of infectious airborne particles and about the importance of this route, compared with droplet or contact transmission. Methods. Airborne particles were collected in an urgent care clinic with use of stationary and personal aerosol samplers. The amounts of airborne influenza A, influenza B, and RSV RNA were determined using real-time quantitative polymerase chain reaction. Health care workers and patients participating in the study were tested for influenza. Results. Seventeen percent of the stationary samplers contained influenza A RNA, 1% contained influenza B RNA, and 32% contained RSV RNA. Nineteen percent of the personal samplers contained influenza A RNA, none contained influenza B RNA, and 38% contained RSV RNA. The number of samplers containing influenza RNA correlated well with the number and location of patients with influenza (r = 0.77). Forty-two percent of the influenza A RNA was in particles ⩽4.1 μm in aerodynamic diameter, and 9% of the RSV RNA was in particles ⩽4.1 μm. Conclusions. Airborne particles containing influenza and RSV RNA were detected throughout a health care facility. The particles were small enough to remain airborne for an extended time and to be inhaled deeply into the respiratory tract. These results support the possibility that influenza and RSV can be transmitted by the airborne route and suggest that further investigation of the potential of these particles to transmit infection is warranted. [ABSTRACT FROM AUTHOR] more...

Background: Welding fumes consist of a wide range of complex metal oxide particles which can be deposited in all regions of the respiratory tract. The welding aerosol is not homogeneous and is generated mostly from the electrode/wire. Over 390,000 welders were reported in the U.S. in 2008 while over 1 million full-time welders were working worldwide. Many health effects are presently under investigation from exposure to welding fumes. Welding fume pulmonary effects have been associated with bronchitis, metal fume fever, cancer and functional changes in the lung. Our investigation focused on the generation of free radicals and reactive oxygen species from stainless and mild steel welding fumes generated by a gas metal arc robotic welder. An inhalation exposure chamber located at NIOSH was used to collect the welding fume particles. Results: Our results show that hydroxyl radicals (.OH) were generated from reactions with H2O2 and after exposure to cells. Catalase reduced the generation of .OH from exposed cells indicating the involvement of H2O2. The welding fume suspension also showed the ability to cause lipid peroxidation, effect O2 consumption, induce H2O2 generation in cells, and cause DNA damage. Conclusion: Increase in oxidative damage observed in the cellular exposures correlated well with .OH generation in size and type of welding fumes, indicating the influence of metal type and transition state on radical production as well as associated damage. Our results demonstrate that both types of welding fumes are able to generate ROS and ROS-related damage over a range of particle sizes; however, the stainless steel fumes consistently showed a significantly higher reactivity and radical generation capacity. The chemical composition of the steel had a significant impact on the ROS generation capacity with the stainless steel containing Cr and Ni causing more damage than the mild steel. Our results suggest that welding fumes may cause acute lung injury. Since type of fume generated, particle size, and elapsed time after generation of the welding exposure are significant factors in radical generation and particle deposition these factors should be considered when developing protective strategies. [ABSTRACT FROM AUTHOR] more...

Many workers worldwide are continually exposed to complex aerosols generated from welding processes. The objective was to assess the effect of inhalation exposure to mild steel (MS) welding fume on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to MS fume at a concentration of 40 mg/m3 × 3 h/day × 3 or 10 days using a robotic welding fume generator. Controls were exposed to filtered air. To assess lung defense responses, a group of animals were intratracheally inoculated with 5 × 104 Listeria monocytogenes 1 day after the last daily exposure. Welding particles were collected during exposure, and chemical composition and particle size were determined. After exposure, lung injury, inflammation, and host defense (bacterial clearance) were measured. The particles were composed of iron (80.6 %) and manganese (14.7 %) with a mass median aerodynamic diameter of 0.31 μ m. No significant difference was observed in lung injury or inflammation after MS fume inhalation at 1, 4, and 11 days after the last exposure. However, there were significantly more bacteria at 3 days after infection in the lungs of the animals exposed to MS fume compared to air controls. Acute exposure of rats to MS fume had no effect on injury and inflammation, but suppressed lung defense responses after infection. More chronic inhalation studies are needed to further examine the immune effects and to elucidate the possible mechanisms of the suppressed lung defense response to infection associated with the inhalation of MS welding fume. [ABSTRACT FROM AUTHOR] more...

Single-walled carbon nanotubes (SWCNT) are being produced in increasing quantities because of high interest in applications resulting from their unique properties. Because of potential respiratory exposures during production and handling, inhalation studies are needed to determine potential toxicity. A generation system was designed to produce respirable aerosol at 5 mg/m3 for a 1-wk animal (mouse) exposure. The starting material used in these experiments was as-produced powder from the high pressure carbon monoxide method that was sieved to number 6 mesh (< 2.3 mm). An acoustic feeder system was developed that handled the SWCNT powder without causing compaction of the material. The feed rate was adjustable, allowing output concentrations as high as 25 mg/m3. The powder particles were reduced in size using a mill that produced high shear forces, tearing the agglomerates apart. The resulting aerosol was size-separated using a settling chamber and two cyclones to produce a respirable aerosol. The mass output efficiency of the entire system for producing a respirable aerosol from bulk material was estimated to be about 10%. [ABSTRACT FROM AUTHOR] more...

Background: We have shown that pulmonary exposure to fine particulate matter (PM) impairs endothelium dependent dilation in systemic arterioles. Ultrafine PM has been suggested to be inherently more toxic by virtue of its increased surface area. The purpose of this study was to determine if ultrafine PM (or nanoparticle) inhalation produces greater microvascular dysfunction than fine PM. Rats were exposed to fine or ultrafine TiO2 aerosols (primary particle diameters of ~1 µm and ~21 nm, respectively) at concentrations which do not alter bronchoalveolar lavage markers of pulmonary inflammation or lung damage. Results: By histopathologic evaluation, no significant inflammatory changes were seen in the lung. However, particle-containing macrophages were frequently seen in intimate contact with the alveolar wall. The spinotrapezius muscle was prepared for in vivo microscopy 24 hours after inhalation exposures. Intraluminal infusion of the Ca2+ ionophore A23187 was used to evaluate endothelium-dependent arteriolar dilation. In control rats, A23187 infusion produced dose-dependent arteriolar dilations. In rats exposed to fine TiO2, A23187 infusion elicited vasodilations that were blunted in proportion to pulmonary particle deposition. In rats exposed to ultrafine TiO2, A23187 infusion produced arteriolar constrictions or significantly impaired vasodilator responses as compared to the responses observed in control rats or those exposed to a similar pulmonary load of fine particles. Conclusion: These observations suggest that at equivalent pulmonary loads, as compared to fine TiO2, ultrafine TiO2 inhalation produces greater remote microvascular dysfunction. [ABSTRACT FROM AUTHOR] more...

Background Influenza virus was used to characterize the efficacy of a cyclone-based, two-stage personal bioaerosol sampler for the collection and size fractionation of aerosolized viral particles. Methods A Collison single-jet nebulizer was used to aerosolize the attenuated FluMist® vaccine into a calm-air settling chamber. Viral particles were captured with bioaerosol samplers that utilize 2 microcentrifuge tubes to collect airborne particulates. The first tube (T1) collects particles greater than 1.8 μm in diameter, while the second tube (T2) collects particles between 1.0 and 1.8 μm, and the back-up filter (F) collects submicron particles. Following aerosolization, quantitative PCR was used to detect and quantify H1N1 and H3N2 influenza strains. Results Based on qPCR results, we demonstrate that aerosolized viral particles were efficiently collected and separated according to aerodynamic size using the two-stage bioaerosol sampler. Most viral particles were collected in T2 (1-1.8 μm) and on the back-up filter (< 1 μm) of the bioaerosol sampler. Furthermore, we found that the detection of viral particles with the two-stage sampler was directly proportional to the collection time. Consequently, viral particle counts were significantly greater at 40 minutes in comparison to 5, 10 and 20 minute aerosol collection points. Conclusions Due to a lack of empirical data, aerosol transmission of influenza is often questioned. Using FluMist®, we demonstrated that a newly developed bioaerosol sampler is able to recover and size fractionate aerosolized viral particles. This sampler should be an important tool for studying viral transmission in clinical settings and may significantly contribute towards understanding the modes of influenza virus transmission. [ABSTRACT FROM AUTHOR] more...

Exposure to fungal aerosols is of concern in indoor environments. However, sampling limitations have previously made it difficult to assess exposures accurately, especially long-term exposures. A prototype personal aerosol sampler, based on cyclone principles and using a 1.5 ml microcentrifuge tube as a particle collection receptacle has been designed and fabricated. Collection efficiency for aerosol particles in the size range of fungal spores has been evaluated for different types of microcentrifuge tubes, together with the effect of a polyethylene glycol coating on the inside of the tube and the effect of adding water to the tube. Monodisperse, fluorescently tagged polymer microspheres with median diameters of 0.5, 1, 2, 3, 6, 11, and 16 µm were used to evaluate sampler performance with particle diameter. The microcentrifuge-tube sampler was tested at flow rates of 2 and 4 liters per minute (l/min). Experimental results indicate that the microcentrifuge-tube sampler has an aspiration efficiency of 100% in calm air for particles up to 16 µm. At 4 l/min, the microcentrifuge-tube sampler is able to collect nearly 100% of particles greater than 3 ìm and >90% of particles between 2.5 and 3 µm. The 50% cutoff size is 1.5 µm. The performance of the sampler did not vary with the different brands of tubes tested or with the presence or absence of a coating on the tube surface. Furthermore, the addition of water to the tube resulted in a slight increase in collection efficiency. A sampling time of 5 h was feasible at 45-50% relative humidity before evaporation led to significant water loss. The cutoff size of 1.5 ìm is comparable to many commercially available bioaerosol samplers. Besides being easy to use, simple to fabricate, and inexpensive, this novel sampler has several advantages over conventional samplers: long-term samples are possible (the limitation of impaction methods); there is no sample transfer loss since the transfer step has been eliminated (the limitation of filter cassettes); laboratory analyses are not dependent solely upon a single analysis method (the limitation of impaction methods), and there is no sampler adherence loss (the limitation of trying to wash microorganisms from filters). In addition, use of the sampler would be applicable in a variety of occupational settings from low bioaerosol concentrations (i.e., indoor environments) to high bioaerosol concentrations (i.e., agricultural setting) by varying sampling time periods and using sensitive analytical methods. [ABSTRACT FROM AUTHOR] more...

A compact, low cost, and easy to operate experimental system was developed for evaluating personal samplers in a calm-air environment. The system can provide uniformly distributed monodisperse microspheres up to 69.7 µm in a quiescent environment for determining sampler efficiencies using a fluorescence method. The reference concentration was measured using one vertical and two horizontal sharp-edged probes. The vertical sampling probe met the criterion for greater than 90% sampling efficiency for upward facing cylindrical probes given by Agarwal and Liu, except at the particle size of 69.7 µm. In addition, the consistent agreement among all three reference sampling probes at all particle sizes tested implied that representative measurements of aerosol concentrations in the test section were achieved. In this study, the RespiCon (Model No. 8522, TSI Inc., St. Paul, MN, USA) and IOM (Cat. No. 225-70, SKC Inc., Eighty Four, PA, USA) personal aerosol samplers were evaluated in the system with air velocities in the sampling region below 1.5 cm/s. The sampling efficiency of the IOM was near 100% at all particle sizes, while the RespiCon matched the conventional respirable and thoracic convention curves but undersampled the inhalable fraction. [ABSTRACT FROM AUTHOR] more...

The purpose of this study was to numerically simulate the performance of an aerosol sampler with a curved, blunt, multi-orificed inlet in order to understand the sampling characteristics of the first prototype of the button personal inhalable aerosol sampler ("button sampler"). Because the button sampler inlet design is too complicated to apply a three-dimensional model, an axisymmetric two-dimensional model was created to be similar in geometry and to simulate the major features of the airflow through the sampler when facing the wind. Particle trajectories were calculated in a variety of wind velocities and were categorized into 5 groups based on their interactions with the curved surface of the sampling plane. Empirical sampling efficiencies of the button sampler for 3 particle sizes were used to adjust the calculated sampling efficiencies in an attempt to improve the accuracy of the two-dimensional axisymmetric model in accounting for interactions between particles and the surface of the inlet of the button sampler. Sampling efficiencies for other particle sizes were then predicted. The results showed that sampling efficiency decreased with increasing particle size up to approximately 40 μm and then remained virtually unchanged at about 35% up to 100 μm. Although the efficiencies were lower than the American Conference of Governmental Industrial Hygienists' (ACGIH) inhalability curve for larger particles, the pattern of the predicted sampling efficiency was quite similar to the ACGIH inhalability curve. Sampling efficiencies for liquid aerosol particles larger than 15 μm were predicted to be noticeably lower than those for solid particles. The results also showed that the multi-orificed curved surface played an important role in establishing a pressure drop with desired flow alignment inside the sampler, thus greatly reducing the wind effect and significantly improving the uniformity of particle deposition on the filter. The less uniform deposition found at high wind velocity can be improved by increasing the sampling flow rate. [ABSTRACT FROM AUTHOR] more...

Historical data on the dust exposures of Chinese workers in metal mines (iron/copper, tin, tungsten) and pottery industries are being used in an ongoing joint Chinese/United States epidemiological study to investigate the exposure–response relationship for the development of silicosis, lung cancer, and other diseases. The historical data include ‘total dust’ concentrations determined by a Chinese method. Information about particle size distribution and the chemical and mineralogical content of airborne particles is generally not available. In addition, the historical Chinese sampling strategy is different from a typical American eight-hour time-weighted average (TWA) sampling strategy, because the Chinese samples were collected for approximately 15 minutes during production so the sample could be compared to their maximum allowable concentration (MAC) standard. Therefore, in order to assess American respirable dust exposure standards in light of the Chinese experience, factors are needed to convert historical Chinese total dust concentrations to respirable dust concentrations. As a part of the joint study to estimate the conversion factors, airborne dust samples were collected in 20 metal mines and 9 pottery factories in China during 1988 and 1989 using three different samplers: 10mm nylon cyclones, multi-stage ‘cassette’ impactors, and the traditional Chinese total dust samplers. More than 100 samples were collected and analysed for each of the three samplers. The study yielded two different estimates of the conversion factor from the Chinese total dust concentrations (measured during production processes) to respirable dust concentrations. The multivariate analysis of variance (MANOVA) reveals that, with a fixed sampling/analysis method, conversion factors were not statistically different among the different job titles within each industry. It also indicates that conversion factors among the industries were not statistically different. However, the two estimates consistently showed that conversion factors were the lowest in the pottery industry. Average conversion factors were then calculated for each of the estimates across the industries studied. A pooled mean conversion factor, 0.25±0.04, was then derived for all the job titles and industries. Respirable dust levels were estimated from the historical ‘total dust’ concentrations collected between 1952 and 1992 by adopting the American standard. [ABSTRACT FROM PUBLISHER] more...