Pulmonary evaluation of whole-body inhalation exposure of polycarbonate (PC) filament 3D printer emissions in rats.

During fused filament fabrication (FFF) 3D printing with polycarbonate (PC) filament, a release of ultrafine particles (UFPs) and volatile organic compounds (VOCs) occurs. This study aimed to determine PC filament printing emission-induced toxicity in rats via whole-body inhalation exposure. Male Sprague Dawley rats were exposed to a single concentration (0.529 mg/m3, 40 nm mean diameter) of the 3D PC filament emissions in a time-course via whole body inhalation for 1, 4, 8, 15, and 30 days (4 hr/day, 4 days/week), and sacrificed 24 hr after the last exposure. Following exposures, rats were assessed for pulmonary and systemic responses. To determine pulmonary injury, total protein and lactate dehydrogenase (LDH) activity, surfactant proteins A and D, total as well as lavage fluid differential cells in bronchoalveolar lavage fluid (BALF) were examined, as well as histopathological analysis of lung and nasal passages was performed. To determine systemic injury, hematological differentials, and blood biomarkers of muscle, metabolic, renal, and hepatic functions were also measured. Results showed that inhalation exposure induced no marked pulmonary or systemic toxicity in rats. In conclusion, inhalation exposure of rats to a low concentration of PC filament emissions produced no significant pulmonary or systemic toxicity.

Multi-instrument assessment of fine and ultrafine titanium dioxide aerosols.

The measurement of fine (diameter: 100 nanometers-2.5 micrometers) and ultrafine (UF: < 100 nanometers) titanium dioxide (TiO2) particles is instrument dependent. Differences in measurements exist between toxicological and field investigations for the same exposure metric such as mass, number, or surface area because of variations in instruments used, operating parameters, or particle-size measurement ranges. Without appropriate comparison, instrument measurements create a disconnect between toxicological and field investigations for a given exposure metric. Our objective was to compare a variety of instruments including multiple metrics including mass, number, and surface area (SA) concentrations for assessing different concentrations of separately aerosolized fine and UF TiO2 particles. The instruments studied were (1) DustTrak™ DRX, (2) personal DataRAMs™ (PDR), (3) GRIMMTM, and (4) diffusion charger (DC). Two devices of each field-study instrument (DRX, PDR, GRIMM, and DC) were used to measure various metrics while adjusting for gravimetric mass concentrations of fine and UF TiO2 particles in controlled chamber tests. An analysis of variance (ANOVA) was used to apportion the variance to inter-instrument (between different instrument-types), inter-device (within instrument), and intra-device components. Performance of each instrument-device was calculated using root mean squared error compared to reference methods: close-faced cassette and gravimetric analysis for mass and scanning mobility particle sizer (SMPS) real-time monitoring for number and SA concentrations. Generally, inter-instrument variability accounted for the greatest (62.6% or more) source of variance for mass, and SA-based concentrations of fine and UF TiO2 particles. However, higher intra-device variability (53.7%) was observed for number concentrations measurements with fine particles compared to inter-instrument variability (40.8%). Inter-device variance range(0.5-5.5%) was similar for all exposure metrics. DRX performed better in measuring mass closer to gravimetric than PDRs for fine and UF TiO2. Number concentrations measured by GRIMMs and SA measurements by DCs were considerably (40.8-86.9%) different from the reference (SMPS) method for comparable size ranges of fine and UF TiO2. This information may serve to aid in interpreting assessments in risk models, epidemiologic studies, and development of occupational exposure limits, relating to health effect endpoints identified in toxicological studies considering similar instruments evaluated in this study.

Influence of Impurities from Manufacturing Process on the Toxicity Profile of Boron Nitride Nanotubes.

The toxicity of boron nitride nanotubes (BNNTs) has been the subject of conflicting reports, likely due to differences in the residuals and impurities that can make up to 30-60% of the material produced based on the manufacturing processes and purification employed. Four BNNTs manufactured by induction thermal plasma process with a gradient of BNNT purity levels achieved through sequential gas purification, water and solvent washing, allowed assessing the influence of these residuals/impurities on the toxicity profile of BNNTs. Extensive characterization including infrared and X-ray spectroscopy, thermogravimetric analysis, size, charge, surface area, and density captured the alteration in physicochemical properties as the material went through sequential purification. The material from each step is screened using acellular and in vitro assays for evaluating general toxicity, mechanisms of toxicity, and macrophage function. As the material increased in purity, there are more high-aspect-ratio particulates and a corresponding distinct increase in cytotoxicity, nuclear factor-κB transcription, and inflammasome activation. There is no alteration in macrophage function after BNNT exposure with all purity grades. The cytotoxicity and mechanism of screening clustered with the purity grade of BNNTs, illustrating that greater purity of BNNT corresponds to greater toxicity.

Developing a Solution for Nasal and Olfactory Transport of Nanomaterials.

With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-Omptm3Mom/MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.

Identification of effective control technologies for additive manufacturing.

Additive manufacturing (AM) refers to several types of processes that join materials to build objects, often layer-by-layer, from a computer-aided design file. Many AM processes release potentially hazardous particles and gases during printing and associated tasks. There is limited understanding of the efficacy of controls including elimination, substitution, administrative, and personal protective technologies to reduce or remove emissions, which is an impediment to implementation of risk mitigation strategies. The Medline, Embase, Environmental Science Collection, CINAHL, Scopus, and Web of Science databases and other resources were used to identify 42 articles that met the inclusion criteria for this review. Key findings were as follows: 1) engineering controls for material extrusion-type fused filament fabrication (FFF) 3-D printers and material jetting printers that included local exhaust ventilation generally exhibited higher efficacy to decrease particle and gas levels compared with isolation alone, and 2) engineering controls for particle emissions from FFF 3-D printers displayed higher efficacy for ultrafine particles compared with fine particles and in test chambers compared with real-world settings. Critical knowledge gaps identified included a need for data: 1) on efficacy of controls for all AM process types, 2) better understanding approaches to control particles over a range of sizes and gas-phase emissions, 3) obtained using a standardized collection approach to facilitate inter-comparison of study results, 4) approaches that go beyond the inhalation exposure pathway to include controls to minimize dermal exposures, and 5) to evaluate not just the engineering tier, but also the prevention-through-design and other tiers of the hierarchy of controls.

Comparison of product safety data sheet ingredient lists with skin irritants and sensitizers present in a convenience sample of light-curing resins used in additive manufacturing.

Material jetting and vat photopolymerization additive manufacturing (AM) processes use liquid resins to build objects. These resins can contain skin irritants and/or sensitizers but product safety data sheets (SDSs) might not declare all ingredients. We characterized elemental and organic skin irritants and sensitizers present in 39 commercial products; evaluated the influence of resin manufacturer, system, color, and AM process type on the presence of irritants and sensitizers; and compared product SDSs to results. Among all products, analyses identified 23 irritant elements, 54 irritant organic substances, 22 sensitizing elements, and 23 sensitizing organic substances; SDSs listed 3, 9, 4, and 6 of these ingredients, respectively. Per product, the number and total mass (an indicator of potential dermal loading) of ingredients varied: five to 17 irritant elements (8.32-4756.65 mg/kg), one to 17 irritant organics (3273 to 356,000 mg/kg), four to 17 sensitizing elements (8.27-4755.63 mg/kg), and one to seven sensitizing organics (15-382,170 mg/kg). Median numbers and concentrations of irritants and sensitizers were significantly influenced by resin system and AM process type. The presence of undeclared irritants and sensitizers in these resins supports the need for more complete information on product SDSs for comprehensive dermal risk assessments.

Evaluation of Pulmonary Effects of 3-D Printer Emissions From Acrylonitrile Butadiene Styrene Using an Air-Liquid Interface Model of Primary Normal Human-Derived Bronchial Epithelial Cells.

This study investigated the inhalation toxicity of the emissions from 3-D printing with acrylonitrile butadiene styrene (ABS) filament using an air-liquid interface (ALI) in vitro model. Primary normal human-derived bronchial epithelial cells (NHBEs) were exposed to ABS filament emissions in an ALI for 4 hours. The mean and mode diameters of ABS emitted particles in the medium were 175 ± 24 and 153 ± 15 nm, respectively. The average particle deposition per surface area of the epithelium was 2.29 × 107 ± 1.47 × 107 particle/cm2, equivalent to an estimated average particle mass of 0.144 ± 0.042 µg/cm2. Results showed exposure of NHBEs to ABS emissions did not significantly affect epithelium integrity, ciliation, mucus production, nor induce cytotoxicity. At 24 hours after the exposure, significant increases in the pro-inflammatory markers IL-12p70, IL-13, IL-15, IFN-γ, TNF-α, IL-17A, VEGF, MCP-1, and MIP-1α were noted in the basolateral cell culture medium of ABS-exposed cells compared to non-exposed chamber control cells. Results obtained from this study correspond with those from our previous in vivo studies, indicating that the increase in inflammatory mediators occur without associated membrane damage. The combination of the exposure chamber and the ALI-based model is promising for assessing 3-D printer emission-induced toxicity.

Towards sustainable additive manufacturing: The need for awareness of particle and vapor releases during polymer recycling, making filament, and fused filament fabrication 3-D printing.

Fused filament fabrication three-dimensional (FFF 3-D) printing is thought to be environmentally sustainable; however, significant amounts of waste can be generated from this technology. One way to improve its sustainability is via distributed recycling of plastics in homes, schools, and libraries to create feedstock filament for printing. Risks from exposures incurred during recycling and reuse of plastics has not been incorporated into life cycle assessments. This study characterized contaminant releases from virgin (unextruded) and recycled plastics from filament production through FFF 3-D printing. Waste polylactic acid (PLA) and acrylonitrile butadiene styrene (ABS) plastics were recycled to create filament; virgin PLA, ABS, high and low density polyethylenes, high impact polystyrene, and polypropylene pellets were also extruded into filament. The release of particles and chemicals into school classrooms was evaluated using standard industrial hygiene methodologies. All tasks released particles that contained hazardous metals (e.g., manganese) and with size capable of depositing in the gas exchange region of the lung, i.e., granulation of waste PLA and ABS (667 to 714 nm) and filament making (608 to 711 nm) and FFF 3-D printing (616 to 731 nm) with waste and virgin plastics. All tasks released vapors, including respiratory irritants and potential carcinogens (benzene and formaldehyde), mucus membrane irritants (acetone, xylenes, ethylbenzene, and methyl methacrylate), and asthmagens (styrene, multiple carbonyl compounds). These data are useful for incorporating risks of exposure to hazardous contaminants in future life cycle evaluations to demonstrate the sustainability and circular economy potential of FFF 3-D printing in distributed spaces.

Particle transfer and adherence to human skin compared with cotton glove and pre-moistened polyvinyl alcohol exposure sampling substrates.

Measurement of skin exposure to particles using interception (e.g., cotton gloves) and removal (e.g., wiping) sampling techniques could be inaccurate because these substrates do not have the same topography and adhesion characteristics as skin. The objective of this study was to compare particle transfer and adherence to cotton gloves, cotton gloves with artificial sebum, and a pre-moistened polyvinyl alcohol (PVA) material with bare human skin (fingertip, palm). Experiments were performed with aluminum oxide powder under standardized conditions for three types of surfaces touched, applied loads, contact times, and powder mass levels. In the final mixed model, the fixed effects of substrate, surface type, applied load, and powder mass and their significant two-way interaction terms explained 71% (transfer) and 74% (adherence) of the observed total variance in measurements. For particle mass transfer, compared with bare skin, bias was -77% (cotton glove with sebum) to +197% (PVA material) and for adherence bias ranged from -40% (cotton glove) to +428% (PVA material), which indicated under- and over-sampling by these substrates, respectively. Dermal exposure assessment would benefit from sampling substrates that better reflect human skin characteristics and more accurately estimate exposures. Mischaracterization of dermal exposure has important implications for exposure and risk assessment.

Particle Size Distributions for Cellulose Nanocrystals Measured by Transmission Electron Microscopy: An Interlaboratory Comparison.

Particle size is a key parameter that must be measured to ensure reproducible production of cellulose nanocrystals (CNCs) and to achieve reliable performance metrics for specific CNC applications. Nevertheless, size measurements for CNCs are challenging due to their broad size distribution, irregular rod-shaped particles, and propensity to aggregate and agglomerate. We report an interlaboratory comparison (ILC) that tests transmission electron microscopy (TEM) protocols for image acquisition and analysis. Samples of CNCs were prepared on TEM grids in a single laboratory, and detailed data acquisition and analysis protocols were provided to participants. CNCs were imaged and the size of individual particles was analyzed in 10 participating laboratories that represent a cross section of academic, industrial, and government laboratories with varying levels of experience with imaging CNCs. The data for each laboratory were fit to a skew normal distribution that accommodates the variability in central location and distribution width and asymmetries for the various datasets. Consensus values were obtained by modeling the variation between laboratories using a skew normal distribution. This approach gave consensus distributions with values for mean, standard deviation, and shape factor of 95.8, 38.2, and 6.3 nm for length and 7.7, 2.2, and 2.9 nm for width, respectively. Comparison of the degree of overlap between distributions for individual laboratories indicates that differences in imaging resolution contribute to the variation in measured widths. We conclude that the selection of individual CNCs for analysis and the variability in CNC agglomeration and staining are the main factors that lead to variations in measured length and width between laboratories.

Biological effects of inhaled hydraulic fracturing sand dust. III. Cytotoxicity and pro-inflammatory responses in cultured murine macrophage cells.

Cultured murine macrophages (RAW 264.7) were used to investigate the effects of fracking sand dust (FSD) for its pro-inflammatory activity, in order to gain insight into the potential toxicity to workers associated with inhalation of FSD during hydraulic fracturing. While the role of respirable crystalline silica in the development of silicosis is well documented, nothing is known about the toxicity of inhaled FSD. The FSD (FSD 8) used in these studies was from an unconventional gas well drilling site. FSD 8was prepared as a 10 mg/ml stock solution in sterile PBS, vortexed for 15 s, and allowed to sit at room temperature for 30 min before applying the suspension to RAW 264.7cells. Compared to PBS controls, cellular viability was significantly decreased after a 24 h exposure to FSD. Intracellular reactive oxygen species (ROS) production and the production of IL-6, TNFα, and endothelin-1 (ET-1) were up-regulated as a result of the exposure, whereas the hydroxyl radical (.OH) was only detected in an acellular system. Immunofluorescent staining of cells against TNFα revealed that FSD 8 caused cellular blebbing, and engulfment of FSD 8 by macrophages was observed with enhanced dark-field microscopy. The observed changes in cellular viability, cellular morphology, free radical generation and cytokine production all confirm that FSD 8 is cytotoxic to RAW 264.7 cells and warrants future studies into the specific pathways and mechanisms by which these toxicities occur.

Pulmonary and systemic toxicity in rats following inhalation exposure of 3-D printer emissions from acrylonitrile butadiene styrene (ABS) filament.

BACKGROUND: Fused filament fabrication 3-D printing with acrylonitrile butadiene styrene (ABS) filament emits ultrafine particulates (UFPs) and volatile organic compounds (VOCs). However, the toxicological implications of the emissions generated during 3-D printing have not been fully elucidated. AIM AND METHODS: The goal of this study was to investigate the in vivo toxicity of ABS-emissions from a commercial desktop 3-D printer. Male Sprague Dawley rats were exposed to a single concentration of ABS-emissions or air for 4 hours/day, 4 days/week for five exposure durations (1, 4, 8, 15, and 30 days). At 24 hours after the last exposure, rats were assessed for pulmonary injury, inflammation, and oxidative stress as well as systemic toxicity. RESULTS AND DISCUSSION: 3-D printing generated particulate with average particle mass concentration of 240 ± 90 µg/m³, with an average geometric mean particle mobility diameter of 85 nm (geometric standard deviation = 1.6). The number of macrophages increased significantly at day 15. In bronchoalveolar lavage, IFN-γ and IL-10 were significantly higher at days 1 and 4, with IL-10 levels reaching a peak at day 15 in ABS-exposed rats. Neither pulmonary oxidative stress responses nor histopathological changes of the lungs and nasal passages were found among the treatments. There was an increase in platelets and monocytes in the circulation at day 15. Several serum biomarkers of hepatic and kidney functions were significantly higher at day 1. CONCLUSIONS: At the current experimental conditions applied, it was concluded that the emissions from ABS filament caused minimal transient pulmonary and systemic toxicity.

Workplace indoor environmental quality and asthma-related outcomes in healthcare workers.

BACKGROUND: Asthma-related health outcomes are known to be associated with indoor moisture and renovations. The objective of this study was to estimate the frequency of these indoor environmental quality (IEQ) factors in healthcare facilities and their association with asthma-related outcomes among workers. METHODS: New York City healthcare workers (n = 2030) were surveyed regarding asthma-related symptoms, and moisture and renovation factors at work and at home during the last 12 months. Questions for workplace moisture addressed water damage (WD), mold growth (MG), and mold odor (MO), while for renovations they addressed painting (P), floor renovations (FR), and wall renovations (WR). Regression models were fit to examine associations between work and home IEQ factors and multiple asthma-related outcomes. RESULTS: Reports of any moisture (n = 728, 36%) and renovations (n = 1412, 70%) at work were common. Workplace risk factors for asthma-related outcomes included the moisture categories of WD by itself, WD with MO (without MG), and WD with MG and MO, and the renovation category with the three factors P, FR, and WR. Reports of home IEQ factors were less frequent and less likely to be associated with health outcomes. Data analyses suggested that MG and/or MO at work and at home had a synergistic effect on the additive scale with a symptom-based algorithm for bronchial hyperresponsiveness. CONCLUSIONS: The current study determined that moisture and renovation factors are common in healthcare facilities, potentially putting workers at risk for asthma-related outcomes. More research is needed to confirm these results, especially prospective studies.

Mitsui-7, heat-treated, and nitrogen-doped multi-walled carbon nanotubes elicit genotoxicity in human lung epithelial cells.

BACKGROUND: The unique physicochemical properties of multi-walled carbon nanotubes (MWCNT) have led to many industrial applications. Due to their low density and small size, MWCNT are easily aerosolized in the workplace making respiratory exposures likely in workers. The International Agency for Research on Cancer designated the pristine Mitsui-7 MWCNT (MWCNT-7) as a Group 2B carcinogen, but there was insufficient data to classify all other MWCNT. Previously, MWCNT exposed to high temperature (MWCNT-HT) or synthesized with nitrogen (MWCNT-ND) have been found to elicit attenuated toxicity; however, their genotoxic and carcinogenic potential are not known. Our aim was to measure the genotoxicity of MWCNT-7 compared to these two physicochemically-altered MWCNTs in human lung epithelial cells (BEAS-2B & SAEC). RESULTS: Dose-dependent partitioning of individual nanotubes in the cell nuclei was observed for each MWCNT material and was greatest for MWCNT-7. Exposure to each MWCNT led to significantly increased mitotic aberrations with multi- and monopolar spindle morphologies and fragmented centrosomes. Quantitative analysis of the spindle pole demonstrated significantly increased centrosome fragmentation from 0.024-2.4 µg/mL of each MWCNT. Significant aneuploidy was measured in a dose-response from each MWCNT-7, HT, and ND; the highest dose of 24 µg/mL produced 67, 61, and 55%, respectively. Chromosome analysis demonstrated significantly increased centromere fragmentation and translocations from each MWCNT at each dose. Following 24 h of exposure to MWCNT-7, ND and/or HT in BEAS-2B a significant arrest in the G1/S phase in the cell cycle occurred, whereas the MWCNT-ND also induced a G2 arrest. Primary SAEC exposed for 24 h to each MWCNT elicited a significantly greater arrest in the G1 and G2 phases. However, SAEC arrested in the G1/S phase after 72 h of exposure. Lastly, a significant increase in clonal growth was observed one month after exposure to 0.024 µg/mL MWCNT-HT & ND. CONCLUSIONS: Although MWCNT-HT & ND cause a lower incidence of genotoxicity, all three MWCNTs cause the same type of mitotic and chromosomal disruptions. Chromosomal fragmentation and translocations have not been observed with other nanomaterials. Because in vitro genotoxicity is correlated with in vivo genotoxic response, these studies in primary human lung cells may predict the genotoxic potency in exposed human populations.

Mouse pulmonary response to dust from sawing Corian®, a solid-surface composite material.

Corian®, a solid-surface composite (SSC), is composed of alumina trihydrate and acrylic polymer. The aim of the present study was to examine the pulmonary toxicity attributed to exposure to SSC sawing dust. Male mice were exposed to either phosphate buffer saline (PBS, control), 62.5, 125, 250, 500, or 1000 µg of SSC dust, or 1000 µg silica (positive control) via oropharyngeal aspiration. Body weights were measured for the duration of the study. Bronchoalveolar lavage fluid (BALF) and tissues were collected for analysis at 1 and 14 days post-exposure. Enhanced-darkfield and histopathologic analysis was performed to assess particle distribution and inflammatory responses. BALF cells and inflammatory cytokines were measured. The geometric mean diameter of SSC sawing dust following suspension in PBS was 1.25 µm. BALF analysis indicated that lactate dehydrogenase (LDH) activity, inflammatory cells, and pro-inflammatory cytokines were significantly elevated in the 500 and 1000 µg SSC exposure groups at days 1 and 14, suggesting that exposure to these concentrations of SSC induced inflammatory responses, in some cases to a greater degree than the silica positive control. Histopathology indicated the presence of acute alveolitis at all doses at day 1, which was largely resolved by day 14. Alveolar particle deposition and granulomatous mass formation were observed in all exposure groups at day 14. The SSC particles were poorly cleared, with 81% remaining at the end of the observation period. These findings demonstrate that SSC sawing dust exposure induces pulmonary inflammation and damage that warrants further investigation. Abbreviations: ANOVA: Analysis of Variance; ATH: Alumina Trihydrate; BALF: Bronchoalveolar Lavage Fluid; Dpg: Geometric Mean Diameter; FE-SEM: Field Emission Scanning Electron Microscopy; IACUC: Institutional Animal Care and Use Committee; IFN-γ: Interferon Gamma; IL-1 Β: Interleukin-1 Beta; IL-10: Interleukin-10; IL-12: Interleukin-12; IL-2: Interleukin-2; IL-4: Interleukin-4; IL-5: Interleukin-5; IL-6: Interleukin-6; KC/GRO: Neutrophil-Activating Protein 3; MMAD: Mass Median Aerodynamic Diameter; PBS: Phosphate-Buffered Saline; PEL: Permissible Exposure Limit; PM: Polymorphonuclear Leukocytes; PNOR: Particles Not Otherwise Regulated; SEM/EDX: Scanning Electron Microscope/Energy-Dispersive X-Ray; SSA: Specific Surface Area; SSC: Solid Surface Composite; TNFα: Tumor Necrosis Factor-Alpha; VOC: Volatile Organic Compounds; σg: Geometric Standard Deviation.

Surface area- and mass-based comparison of fine and ultrafine nickel oxide lung toxicity and augmentation of allergic response in an ovalbumin asthma model.

Background: The correlation of physico-chemical properties with mechanisms of toxicity has been proposed as an approach to predict the toxic potential of the vast number of emerging nanomaterials. Although relationships have been established between properties and the acute pulmonary inflammation induced by nanomaterials, properties' effects on other responses, such as exacerbation of respiratory allergy, have been less frequently explored.Methods: In this study, the role of nickel oxide (NiO) physico-chemical properties in the modulation of ovalbumin (OVA) allergy was examined in a murine model. Results: 181 nm fine (NiO-F) and 42 nm ultrafine (NiO-UF) particles were characterized and incorporated into a time course study where measured markers of pulmonary injury and inflammation were associated with NiO particle surface area. In the OVA model, exposure to NiO, irrespective of any metric was associated with elevated circulating total IgE levels. Serum and lung cytokine levels were similar with respect to NiO surface area. The lower surface area was associated with an enhanced Th2 profile, whereas the higher surface area was associated with a Th1-dominant profile. Surface area-normalized groups also exhibited similar alterations in OVA-specific IgE levels and lung neutrophil number. However, lung eosinophil number and allergen challenge-induced alterations in lung function related more to particle size, wherein NiO-F was associated with an increased enhanced pause response and NiO-UF was associated with increased lung eosinophil burden.Conclusions: Collectively, these findings suggest that although NiO surface area correlates best with acute pulmonary injury and inflammation following respiratory exposure, other physico-chemical properties may contribute to the modulation of immune responses in the lung.

Particle and organic vapor emissions from children's 3-D pen and 3-D printer toys.

Objective: Fused filament fabrication "3-dimensional (3-D)" printing has expanded beyond the workplace to 3-D printers and pens for use by children as toys to create objects.Materials and methods: Emissions from two brands of toy 3-D pens and one brand of toy 3-D printer were characterized in a 0.6 m3 chamber (particle number, size, elemental composition; concentrations of individual and total volatile organic compounds (TVOC)). The effects of print parameters on these emission metrics were evaluated using mixed-effects models. Emissions data were used to model particle lung deposition and TVOC exposure potential.Results: Geometric mean particle yields (106-1010 particles/g printed) and sizes (30-300 nm) and TVOC yields (

A field evaluation of a single sampler for respirable and inhalable indium and dust measurements at an indium-tin oxide manufacturing facility.

Indium-tin oxide production has increased greatly in the last 20 years subsequent to increased global demand for touch screens and photovoltaics. Previous studies used measurements of indium in blood as an indicator of indium exposure and observed associations with adverse respiratory outcomes. However, correlations between measurements of blood indium and airborne respirable indium are inconsistent, in part because of the long half-life of indium in blood, but also because respirable indium measurements do not incorporate inhalable indium that can contribute to the observed biological burden. Information is lacking on relationships between respirable and inhalable indium exposure, which have implications for biological indicators like blood indium. The dual IOM sampler includes the foam disc insert and can simultaneously collect respirable and inhalable aerosol. Here, the field performance of the dual IOM sampler was evaluated by comparing performance with the respirable cyclone and traditional IOM for respirable and inhalable indium and dust exposure, respectively. Side-by-side area air samples were collected throughout an indium-tin oxide manufacturing facility. Cascade impactors were used to determine particle size distribution. Several statistical methods were used to evaluate the agreement between the pairs of samplers including calculating the concordance correlation coefficient and its accuracy and precision components. One-way ANOVA was used to evaluate the effect of dust concentration on sampler differences. Respirable indium measurements showed better agreement (concordance correlation coefficient: 0.932) compared to respirable dust measurements (concordance correlation coefficient: 0.777) with significant differences observed in respirable dust measurements. The dual IOM measurements had high agreement with the traditional IOM for inhalable indium (concordance correlation coefficient: 0.997) but lower agreement for inhalable dust (concordance correlation coefficient: 0.886 and accuracy: 0.896) with a significantly large mean bias (-146.9 µg/m3). Dust concentration significantly affected sampler measurements of inhalable dust and inhalable indium. Results from this study suggest that the dual IOM is a useful single sampler for simultaneous measurements of occupational exposure to respirable and inhalable indium.

Headspace analysis for screening of volatile organic compound profiles of electronic juice bulk material.

The use of electronic nicotine delivery systems continues to gain popularity, and there is concern for potential health risks from inhalation of aerosol and vapor produced by these devices. An analytical method was developed that provided quantitative and qualitative chemical information for characterizing the volatile constituents of bulk electronic cigarette liquids (e-liquids) using a static headspace technique. Volatile organic compounds (VOCs) were screened from a convenience sample of 146 e-liquids by equilibrating 1 g of each e-liquid in amber vials for 24 h at room temperature. Headspace was transferred to an evacuated canister and quantitatively analyzed for 20 VOCs as well as tentatively identified compounds using a preconcentrator/gas chromatography/mass spectrometer system. The e-liquids were classified into flavor categories including brown, fruit, hybrid dairy, menthol, mint, none, tobacco, and other. 2,3-Butanedione was found at the highest concentration in brown flavor types, but was also found in fruit, hybrid dairy, and menthol flavor types. Benzene was observed at concentrations that are concerning given the carcinogenicity of this compound (max 1.6 ppm in a fruit flavor type). The proposed headspace analysis technique coupled with partition coefficients allows for a rapid and sensitive prediction of the volatile content in the liquid. The technique does not require onerous sample preparation, dilution with organic solvents, or sampling at elevated temperatures. Static headspace screening of e-liquids allows for the identification of volatile chemical constituents which is critical for identifying and controlling emission of potentially hazardous constituents in the workplace.

Three-dimensional printing with nano-enabled filaments releases polymer particles containing carbon nanotubes into air.

Fused deposition modeling (FDM™) 3-dimensional printing uses polymer filament to build objects. Some polymer filaments are formulated with additives, though it is unknown if they are released during printing. Three commercially available filaments that contained carbon nanotubes (CNTs) were printed with a desktop FDM™ 3-D printer in a chamber while monitoring total particle number concentration and size distribution. Airborne particles were collected on filters and analyzed using electron microscopy. Carbonyl compounds were identified by mass spectrometry. The elemental carbon content of the bulk CNT-containing filaments was 1.5 to 5.2 wt%. CNT-containing filaments released up to 1010 ultrafine (d < 100 nm) particles/g printed and 106 to 108 respirable (d ~0.5 to 2 µm) particles/g printed. From microscopy, 1% of the emitted respirable polymer particles contained visible CNTs. Carbonyl emissions were observed above the limit of detection (LOD) but were below the limit of quantitation (LOQ). Modeling indicated that, for all filaments, the average proportional lung deposition of CNT-containing polymer particles was 6.5%, 5.7%, and 7.2% for the head airways, tracheobronchiolar, and pulmonary regions, respectively. If CNT-containing polymer particles are hazardous, it would be prudent to control emissions during use of these filaments.