Welding fumes are a Group 1 (carcinogenic to humans) carcinogen as classified by the International Agency for Research on Cancer. The process of welding creates inhalable fumes rich in iron (Fe) that may also contain known carcinogenic metals such as chromium (Cr) and nickel (Ni). Epidemiological evidence has shown that both mild-steel (Fe-rich) and stainless steel (Fe-rich + Cr + Ni) welding fume exposure increase lung cancer risk, and experimental animal data support these findings. Copper-nickel (CuNi) welding processes have not been investigated in the context of lung cancer. Cu is intriguing, however, given the role of Cu in carcinogenesis and cancer therapeutics. This study examines the potential for a CuNi fume to induce mechanistic key characteristics of carcinogenesis in vitro and to promote lung tumorigenesis, using a two-stage mouse bioassay, in vivo. Male A/J mice, initiated with 3-methylcholanthrene (MCA; 10 µg/g), were exposed to CuNi fumes or air by whole-body inhalation for nine weeks (low-deposition-LD and high deposition-HD) then sacrificed at 30 weeks. In BEAS-2B cells, the CuNi fume induced micronuclei and caused DNA damage as measured by γ-H2AX. The fume exhibited high reactivity and a dose response in cytotoxicity and oxidative stress. In vivo, MCA/CuNi HD and LD significantly decreased lung tumor size and adenomas. MCA/CuNi HD exposure significantly decreased gross-evaluated tumor number. In summary, the CuNi fume in vitro exhibited characteristics of a carcinogen, but in vivo the exposure resulted in smaller tumors, fewer adenomas, less hyperplasia severity, and with the HD exposure, less overall lung lesion/tumors.

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/m(3), 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.

Material extrusion-type fused filament fabrication (FFF) 3-D printing is a valuable tool for education. During FFF 3-D printing, thermal degradation of the polymer releases small particles and chemicals, many of which are hazardous to human health. In this study, particle and chemical emissions from 10 different filaments made from virgin (never printed) and recycled polymers were used to print the same object at the polymer manufacturer's recommended nozzle temperature ("normal") and at a temperature higher than recommended ("hot") to simulate the real-world scenarios of a person intentionally or unknowingly printing on a machine with a changed setting. Emissions were evaluated in a college teaching laboratory using standard sampling and analytical methods. From mobility sizer measurements, particle number-based emission rates were 81 times higher; the proportion of ultrafine particles (diameter <100 nm) were 4% higher, and median particle sizes were a factor of 2 smaller for hot-temperature prints compared with normal-temperature prints (all p-values <0.05). There was no difference in emission characteristics between recycled and virgin acrylonitrile butadiene styrene and polylactic acid polymer filaments. Reducing contaminant release from FFF 3-D printers in educational settings can be achieved using the hierarchy of controls: (1) elimination/substitution (e.g., training students on principles of prevention-through-design, limiting the use of higher emitting polymer when possible); (2) engineering controls (e.g., using local exhaust ventilation to directly remove contaminants at the printer or isolating the printer from students); (3) administrative controls such as password protecting printer settings and establishing and enforcing adherence to a standard operating procedure based on a proper risk assessment for the setup and use (e.g., limiting the use of temperatures higher than those specified for the filaments used); and (4) maintenance of printers.

The literature on emissions during material extrusion additive manufacturing with 3-D printers is expanding; however, there is a paucity of data for large-format additive manufacturing (LFAM) machines that can extrude high-melt-temperature polymers. Emissions from two LFAM machines were monitored during extrusion of six polymers: acrylonitrile butadiene styrene (ABS), polycarbonate (PC), high-melt-temperature polysulfone (PSU), poly(ether sulfone) (PESU), polyphenylene sulfide (PPS), and Ultem (poly(ether imide)). Particle number, total volatile organic compound (TVOC), carbon monoxide (CO), and carbon dioxide (CO(2)) concentrations were monitored in real-time. Particle emission rate values (no./min) were as follows: ABS (1.7 × 10(11) to 7.7 × 10(13)), PC (5.2 × 10(11) to 3.6 × 10(13)), Ultem (5.7 × 10(12) to 3.1 × 10(13)), PPS (4.6 × 10(11) to 6.2 × 10(12)), PSU (1.5 × 10(12) to 3.4 × 10(13)), and PESU (2.0 to 5.0 × 10(13)). For print jobs where the mass of extruded polymer was known, particle yield values (g(-1) extruded) were as follows: ABS (4.5 × 10(8) to 2.9 × 10(11)), PC (1.0 × 10(9) to 1.7 × 10(11)), PSU (5.1 × 10(9) to 1.2 × 10(11)), and PESU (0.8 × 10(11) to 1.7 × 10(11)). TVOC emission yields ranged from 0.005 mg/g extruded (PESU) to 0.7 mg/g extruded (ABS). The use of wall-mounted exhaust ventilation fans was insufficient to completely remove airborne particulate and TVOC from the print room. Real-time CO monitoring was not a useful marker of particulate and TVOC emission profiles for Ultem, PPS, or PSU. Average CO(2) and particle concentrations were moderately correlated (r (s) = 0.76) for PC polymer. Extrusion of ABS, PC, and four high-melt-temperature polymers by LFAM machines released particulate and TVOC at levels that could warrant consideration of engineering controls. LFAM particle emission yields for some polymers were similar to those of common desktop-scale 3-D printers.

Extrusion of high-melt-temperature polymers on large-format additive manufacturing (LFAM) machines releases particles and gases, though there is no data describing their physical and chemical characteristics. Emissions from two LFAM machines were monitored during extrusion of acrylonitrile butadiene styrene (ABS) and polycarbonate (PC) polymers as well as high-melt-temperature Ultem (poly(ether imide)), polysulfone (PSU), poly(ether sulfone) (PESU), and polyphenylene sulfide (PPS) polymers. Filter samples of particles were collected for quantification of elements and bisphenol A and S (BPA, BPS) and visualization of morphology. Individual gases were quantified on substance-specific media. Aerosol sampling demonstrated that concentrations of elements were generally low for all polymers, with a maximum of 1.6 mg/m(3) for iron during extrusion of Ultem. BPA, an endocrine disruptor, was released into air during extrusion of PC (range: 0.4 ± 0.1 to 21.3 ± 5.3 μg/m(3)). BPA and BPS (also an endocrine disruptor) were released into air during extrusion of PESU (BPA, 2.0-8.7 μg/m(3); BPS, 0.03-0.07 μg/m(3)). Work surfaces and printed parts were contaminated with BPA (<8-587 ng/100 cm(2)) and BPS (<0.22-2.5 ng/100 cm(2)). Gas-phase sampling quantified low levels of respiratory irritants (phenol, SO(2), toluene, xylenes), possible or known asthmagens (caprolactam, methyl methacrylate, 4-oxopentanal, styrene), and possible occupational carcinogens (benzene, formaldehyde, acetaldehyde) in air. Characteristics of particles and gases released by high-melt-temperature polymers during LFAM varied, which indicated the need for polymer-specific exposure and risk assessments. The presence of BPA and BPS on surfaces revealed a previously unrecognized source of dermal exposure for additive manufacturing workers using PC and PESU polymers.

Puff Bar, one of the latest designs of e-cigarettes, heats a mixture of liquid using a battery-powered coil at certain temperatures to emit aerosol. This study presents a mass-based characterization of emissions from seven flavors of Puff Bar devices by aerosolizing with three puff topographies [(puff volume: 55 < 65 < 75-mL) within 4-seconds at 30-seconds interval]. We evaluated the effects of puff topographies on heating temperatures; characterized particles using a cascade impactor; and measured volatile carbonyl compounds (VCCs). Modeled dosimetry and calculated mass median aerodynamic diameters (MMADs) were used to estimate regional, total respiratory deposition of the inhaled aerosol and exhaled fractions that could pose secondhand exposure risk. Temperatures of Puff Bar e-liquids increased with increasing puff volumes: 55 mL (116.6 C), 65 mL (128.3 C), and 75 mL (168.9 C). Flavor types significantly influenced MMADs, total mass of particles, and VCCs (g/puff: 2.15-2.30) in Puff Bar emissions (p < 0.05). Increasing puff volume (mL:55 < 65 < 75) significantly increased total mass (mg/puff: 4.6 < 5.6 < 6.2) of particles without substantially changing MMADs (1m:1.02 0.99 0.98). Aerosol emissions were estimated to deposit in the pulmonary region of e-cigarette user (4144%), which could have toxicological importance. More than 2/3 (6777%) of inhaled particles were estimated to be exhaled by users, which could affect bystanders. The VCCs measured contained carcinogensformaldehyde (29.6%) and acetaldehyde (16.4%)as well as respiratory irritants: acetone (23.9%), isovaleraldehyde (14.5%), and acrolein (4.9%). As Puff Bar emissions contain respirable particles and harmful chemicals, efforts should be made to minimize exposures, especially in indoor settings where people (including vulnerable populations) spend most of their life-time. Copyright 2023 American Association for Aerosol Research. , This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law.

Puff Bar™, one of the latest designs of e-cigarettes, heats a mixture of liquid using a battery-powered coil at certain temperatures to emit aerosol. This study presents a mass-based characterization of emissions from seven flavors of Puff Bar™ devices by aerosolizing with three puff topographies [(puff volume: 55 < 65 < 75-mL) within 4-seconds at 30-seconds interval]. We evaluated the effects of puff topographies on heating temperatures; characterized particles using a cascade impactor; and measured volatile carbonyl compounds (VCCs). Modeled dosimetry and calculated mass median aerodynamic diameters (MMADs) were used to estimate regional, total respiratory deposition of the inhaled aerosol and exhaled fractions that could pose secondhand exposure risk. Temperatures of Puff Bar™ e-liquids increased with increasing puff volumes: 55 mL (116.6 °C), 65 mL (128.3 °C), and 75 mL (168.9 °C). Flavor types significantly influenced MMADs, total mass of particles, and VCCs (µg/puff: 2.15-2.30) in Puff Bar™ emissions (p < 0.05). Increasing puff volume (mL:55 < 65 < 75) significantly increased total mass (mg/puff: 4.6 < 5.6 < 6.2) of particles without substantially changing MMADs (∼1µm:1.02 ∼ 0.99 ∼ 0.98). Aerosol emissions were estimated to deposit in the pulmonary region of e-cigarette user (41–44%), which could have toxicological importance. More than 2/3 (67–77%) of inhaled particles were estimated to be exhaled by users, which could affect bystanders. The VCCs measured contained carcinogens—formaldehyde (29.6%) and acetaldehyde (16.4%)—as well as respiratory irritants: acetone (23.9%), isovaleraldehyde (14.5%), and acrolein (4.9%). As Puff Bar™ emissions contain respirable particles and harmful chemicals, efforts should be made to minimize exposures, especially in indoor settings where people (including vulnerable populations) spend most of their life-time. Copyright © 2023 American Association for Aerosol Research. ©, This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law.

The measurement of fine (diameter: 100 nanometers-2.5 micrometers) and ultrafine (UF: < 100 nanometers) titanium dioxide (TiO(2)) 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 TiO(2) particles. The instruments studied were (1) DustTrak™ DRX, (2) personal DataRAMs™ (PDR), (3) GRIMM(TM), 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 TiO(2) 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 TiO(2) 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 TiO(2). 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 TiO(2). 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.

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.

Vat photopolymerization (VP), a type of additive manufacturing process that cures resin to build objects, can emit potentially hazardous particles and gases. We evaluated two VP technologies, stereolithography (SLA) and digital light processing (DLP), in three separate environmental chambers to understand task-based impacts on indoor air quality. Airborne particles, total volatile organic compounds (TVOCs), and/or specific volatile organic compounds (VOCs) were monitored during each task to evaluate their exposure potential. Regardless of duration, all tasks released particles and organic gases, though concentrations varied between SLA and DLP processes and among tasks. Maximum particle concentrations reached 1200 #/cm3 and some aerosols contained potentially hazardous elements such as barium, chromium, and manganese. TVOC concentrations were highest for the isopropyl alcohol (IPA) rinsing, soaking, and drying post-processing tasks (up to 36.8 mg/m3), lowest for the resin pouring pre-printing, printing, and resin recovery post-printing tasks (up to 0.1 mg/m3), and intermediate for the curing post-processing task (up to 3 mg/m3). Individual VOCs included, among others, the potential occupational carcinogen acetaldehyde and the immune sensitizer 2-hydroxypropyl methacrylate (pouring, printing, recovery, and curing tasks). Careful consideration of all tasks is important for the development of strategies to minimize indoor air pollution and exposure potential from VP processes. © 2022 by the authors.

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.

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 (8.32-4756.65mg/kg), one to 17 irritant organics (3273 to 356,000mg/kg), four to 17 sensitizing elements (8.27-4755.63mg/kg), and one to seven sensitizing organics (15-382,170mg/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.

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 × 10(7) ± 1.47 × 10(7) particle/cm(2), equivalent to an estimated average particle mass of 0.144 ± 0.042 μg/cm(2). 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.

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-Omp(tm3Mom)/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.

Electronic cigarette, or vaping, products are used to heat an e-liquid to form an aerosol (liquid droplets suspended in gas) that the user inhales; a portion of this aerosol deposits in their respiratory tract and the remainder is exhaled, thereby potentially creating opportunity for secondhand exposure to bystanders (e.g., in homes, automobiles, and workplaces). Particle size, a critical factor in respiratory deposition (and therefore potential for secondhand exposure), could be influenced by e-liquid composition. Hence, the purposes of this study were to (1) test the influence of laboratory-prepared e-liquid composition [ratio of propylene glycol (PG) to vegetable glycerin (VG) humectants, nicotine, and flavorings] on particle size distribution and (2) model respiratory dosimetry. All e-liquids were aerosolized using a second-generation reference e-cigarette. We measured particle size distribution based on mass using a low-flow cascade impactor (LFCI) and size distribution based on number using real-time mobility sizers. Mass median aerodynamic diameters (MMADs) of aerosol from e-liquids that contained only humectants were significantly larger compared with e-liquids that contained flavorings or nicotine (p = 0.005). Humectant ratio significantly influenced MMADs; all aerosols from e-liquids prepared with 70:30 PG:VG were significantly larger compared with e-liquids prepared with 30:70 PG:VG (p = 0.017). In contrast to the LFCI approach, the high dilution and sampling flow rate of a fast mobility particle sizer strongly influenced particle size measurements (i.e., all calculated MMAD values were < 75 nm). Dosimetry modeling using LFCI data indicated that a portion of inhaled particles will deposit throughout the respiratory tract, though statistical differences in aerosol MMADs among e-liquid formulations did not translate into large differences in deposition estimates. A portion of inhaled aerosol will be exhaled and could be a source for secondhand exposure. Use of laboratory-prepared e-liquids and a reference e-cigarette to standardize aerosol generation and a LFCI to measure particle size distribution without dilution represents an improved method to characterize physical properties of volatile aerosol particles and permitted determination of MMAD values more representative of e-cigarette aerosol in situ, which in turn, can help to improve dose modeling for users and bystanders.

As of February 18, 2020, the e-cigarette, or vaping, product use associated lung injury (EVALI) outbreak caused the hospitalization of a total of 2,807 patients and claimed 68 lives in the United States. Though investigations have reported a strong association with vitamin E acetate (VEA), evidence from reported EVALI cases is not sufficient to rule out the contribution of other chemicals of concern, including chemicals in either THC or non-THC products. This study characterized chemicals evolved when diluent oils were heated to temperatures that mimic e-cigarette, or vaping, products (EVPs) to investigate production of potentially toxic chemicals that might have caused lung injury. VEA, vitamin E, coconut, and medium chain triglyceride (MCT) oil were each diluted with ethanol and then tested for constituents and impurities using a gas chromatograph mass spectrometer (GC/MS). Undiluted oils were heated at 25°C (control), 150°C, and 250°C in an inert chamber to mimic a range of temperatures indicative of aerosolization from EVPs. Volatilized chemicals were collected using thermal desorption tubes, analyzed using a GC/MS, and identified. Presence of identified chemicals was confirmed using retention time and ion spectra matching with analytic standards. Direct analysis of oils, as received, revealed that VEA and vitamin E were the main constituents of their oils, and coconut and MCT oils were nearly identical having two main constituents: glycerol tricaprylate and 2-(decanoyloxy) propane-1,3-diyl dioctanoate. More chemicals were measured and with greater intensities when diluent oils were heated at 250°C compared to 150°C and 25°C. Vitamin E and coconut/MCT oils produced different chemical emissions. The presence of some identified chemicals is of potential health consequence because many are known respiratory irritants and acute respiratory toxins. Exposure to a mixture of hazardous chemicals may be relevant to the development or exacerbation of EVALI, especially when in concert with physical damage caused by lung deposition of aerosols produced by aerosolizing diluent oils.

The current fourth generation ("pod-style") electronic cigarette, or vaping, products (EVPs) heat a liquid ("e-liquid") contained in a reservoir ("pod") using a battery-powered coil to deliver aerosol into the lungs. A portion of inhaled EVP aerosol is estimated as exhaled, which can present a potential secondhand exposure risk to bystanders. The effects of modifiable factors using either a prefilled disposable or refillable pod-style EVPs on aerosol particle size distribution (PSD) and its respiratory deposition are poorly understood. In this study, the influence of up to six puff profiles (55-, 65-, and 75-ml puff volumes per 6.5 and 7.5 W EVP power settings) on PSD was evaluated using a popular pod-style EVP (JUUL(®) brand) and a cascade impactor. JUUL(®) brand EVPs were used to aerosolize the manufacturers' e-liquids in their disposable pods and laboratory prepared "reference e-liquid" (without flavorings or nicotine) in refillable pods. The modeled dosimetry and calculated aerosol mass median aerodynamic diameters (MMADs) were used to estimate regional respiratory deposition. From these results, exhaled fraction of EVP aerosols was calculated as a surrogate of the secondhand exposure potential. Overall, MMADs did not differ among puff profiles, except for 55- and 75-ml volumes at 7.5 W (p < 0.05). For the reference e-liquid, MMADs ranged from 1.02 to 1.23 μm and dosimetry calculations predicted that particles would deposit in the head region (36-41%), in the trachea-bronchial (TB) region (19-21%), and in the pulmonary region (40-43%). For commercial JUUL(®) e-liquids, MMADs ranged from 0.92 to 1.67 μm and modeling predicted that more particles would deposit in the head region (35-52%) and in the pulmonary region (30-42%). Overall, 30-40% of the particles aerosolized by a pod-style EVP were estimated to deposit in the pulmonary region and 50-70% of the inhaled EVP aerosols could be exhaled; the latter could present an inhalational hazard to bystanders in indoor occupational settings. More research is needed to understand the influence of other modifiable factors on PSD and exposure potential.

Electronic cigarette, or vaping, products (EVP) heat liquids ("e-liquids") that contain substances (licit or illicit) and deliver aerosolized particles into the lungs. Commercially available oils such as Vitamin-E-acetate (VEA), Vitamin E oil, coconut, and medium chain triglycerides (MCT) were often the constituents of e-liquids associated with an e-cigarette, or vaping, product use-associated lung injury (EVALI). The objective of this study was to evaluate the mass-based physical characteristics of the aerosolized e-liquids prepared using these oil diluents. These characteristics were particle size distributions for modeling regional respiratory deposition and puff-based total aerosol mass for estimating the number of particles delivered to the respiratory tract. Four types of e-liquids were prepared by adding terpenes to oil diluents individually: VEA, Vitamin E oil, coconut oil, and MCT. A smoking machine was used to aerosolize each e-liquid at a predetermined puff topography (volume of 55 ml for 3 s with 30-s intervals between puffs). A cascade impactor was used to collect the size-segregated aerosol for calculating the mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD). The respiratory deposition of EVP aerosols on inhalation was estimated using the Multiple-Path Particle Dosimetry model. From these results, the exhaled fraction of EVP aerosols was calculated as a surrogate of secondhand exposure potential. The MMAD of VEA (0.61 μm) was statistically different compared to MCT (0.38 μm) and coconut oil (0.47 μm) but not to Vitamin E oil (0.58 μm); p < 0.05. Wider aerosol size distribution was observed for VEA (GSD 2.35) and MCT (GSD 2.08) compared with coconut oil (GSD 1.53) and Vitamin E oil (GSD 1.55). Irrespective of the statistical differences between MMADs, dosimetry modeling resulted in the similar regional and lobular deposition of particles for all e-liquids in the respiratory tract. The highest (~0.08 or more) fractional deposition was predicted in the pulmonary region, which is consistent as the site of injury among EVALI cases. Secondhand exposure calculations indicated that a substantial amount of EVP aerosols could be exhaled, which has potential implications for bystanders. The number of EVALI cases has declined with the removal of VEA; however, further research is required to investigate the commonly available commercial ingredients used in e-liquid preparations.

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. © 2021

This comprehensive review introduces occupational (industrial) hygienists and toxicologists to the seven basic additive manufacturing (AM) process categories. Forty-six articles were identified that reported real-world measurements for all AM processes, except sheet lamination. Particles released from powder bed fusion (PBF), material jetting (MJ), material extrusion (ME), and directed energy deposition (DED) processes exhibited nanoscale to submicron scale; real-time particle number (mobility sizers, condensation nuclei counters, miniDiSC, electrical diffusion batteries) and surface area monitors (diffusion chargers) were generally sufficient for these processes. Binder jetting (BJ) machines released particles up to 8.5 µm; optical particle sizers (number) and laser scattering photometers (mass) were sufficient for this process. PBF and DED processes (powdered metallic feedstocks) released particles that contained respiratory irritants (chromium, molybdenum), central nervous system toxicants (manganese), and carcinogens (nickel). All process categories, except those that use metallic feedstocks, released organic gases, including (but not limited to), respiratory irritants (toluene, xylenes), asthmagens (methyl methacrylate, styrene), and carcinogens (benzene, formaldehyde, acetaldehyde). Real-time photoionization detectors for total volatile organics provided useful information for processes that utilize polymer feedstock materials. More research is needed to understand 1) facility-, machine-, and feedstock-related factors that influence emissions and exposures, 2) dermal exposure and biological burden, and 3) task-based exposures. Harmonized emissions monitoring and exposure assessment approaches are needed to facilitate inter-comparison of study results. Improved understanding of AM process emissions and exposures is needed for hygienists to ensure appropriate health and safety conditions for workers and for toxicologists to design experimental protocols that accurately mimic real-world exposure conditions.ABBREVIATIONS ABS : acrylonitrile butadiene styrene; ACGIH® TLV® : American Conference of Governmental Industrial Hygienists Threshold Limit Value; ACH : air change per hour; AM : additive manufacturing; ASA : acrylonitrile styrene acrylate; AVP : acetone vapor polishing; BJ : binder jetting; CAM-LEM : computer-aided manufacturing of laminated engineering materials; CNF : carbon nanofiber; CNT : carbon nanotube; CP : co-polyester; CNC : condensation nuclei counter; CVP : chloroform vapor polishing; DED : directed energy deposition; DLP : digital light processing; EBM : electron beam melting; EELS : electron energy loss spectrometry; EDB : electrical diffusion batteries; EDX : energy dispersive x-ray analyzer; ER : emission rate; FDM™ : fused deposition modeling; FFF : fused filament fabrication; IAQ : indoor air quality; LSP : laser scattering photometer; LCD : liquid crystal display; LDSA : lung deposited particle surface area; LOD : limit of detection; LOM : laminated object manufacturing; LOQ : limit of quantitation; MCE : mixed cellulose ester filter; ME : material extrusion; MJ : material jetting; OEL : occupational exposure limit; OPS : optical particle sizer; PBF : powder bed fusion; PBZ : personal breathing zone; PC : polycarbonate; PEEK : poly ether ether ketone; PET : polyethylene terephthalate; PETG : Polyethylene terephthalate glycol; PID : photoionization detector; PLA : polylactic acid; PM(1) : particulate matter with aerodynamic diameter less than 1 µm; PM(2.5) : particulate matter with aerodynamic diameter less than 2.5 µm; PM(10) : particulate matter with aerodynamic diameter less than 10 µm; PSL : plastic sheet lamination; PVA : polyvinyl alcohol; REL : recommended exposure limit; SDL : selective deposition lamination; SDS : safety data sheet; SEM : scanning electron microscopy; SL : sheet lamination; SLA : stereolithography; SLM : selective laser melting; SMPS : scanning mobility particle sizer; SVOC : semi-volatile organic compound; TEM : transmission electron microscopy; TGA : thermal gravimetric analysis; TPU : thermo polyurethane; UAM : ultrasonic additive manufacturing; UC : ultrasonic consolidation; TVOC : total volatile organic compounds; TWA : time-weighted average; VOC : volatile organic compound; VP : vat photopolymerization.

Electronic cigarettes (e-cigarettes) were introduced in the United States in 2007 and by 2014 they were the most popular tobacco product amongst youth and had overtaken use of regular tobacco cigarettes. E-cigarettes are used to aerosolize a liquid (e-liquid) that the user inhales. Flavorings in e-liquids is a primary reason for youth to initiate use of e-cigarettes. Evidence is growing in the scientific literature that inhalation of some flavorings is not without risk of harm. In this review, 67 original articles (primarily cellular in vitro) on the toxicity of flavored e-liquids were identified in the PubMed and Scopus databases and evaluated critically. At least 65 individual flavoring ingredients in e-liquids or aerosols from e-cigarettes induced toxicity in the respiratory tract, cardiovascular and circulatory systems, skeletal system, and skin. Cinnamaldehyde was most frequently reported to be cytotoxic, followed by vanillin, menthol, ethyl maltol, ethyl vanillin, benzaldehyde and linalool. Additionally, modern e-cigarettes can be modified to aerosolize cannabis as dried plant material or a concentrated extract. The U.S. experienced an outbreak of lung injuries, termed e-cigarette, or vaping, product use-associated lung injury (EVALI) that began in 2019; among 2,022 hospitalized patients who had data on substance use (as of January 14, 2020), 82% reported using a delta-9-tetrahydrocannabinol (main psychoactive component in cannabis) containing e-cigarette, or vaping, product. Our literature search identified 33 articles related to EVALI. Vitamin E acetate, a diluent and thickening agent in cannabis-based products, was strongly linked to the EVALI outbreak in epidemiologic and laboratory studies; however, e-liquid chemistry is highly complex, and more than one mechanism of lung injury, ingredient, or thermal breakdown product may be responsible for toxicity. More research is needed, particularly with regard to e-cigarettes (generation, power settings, etc.), e-liquids (composition, bulk or vaped form), modeled systems (cell type, culture type, and dosimetry metrics), biological monitoring, secondhand exposures and contact with residues that contain nicotine and flavorings, and causative agents and mechanisms of EVALI toxicity.

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.

BACKGROUND: Carbon nanotubes and nanofibers (CNT/F) have known toxicity but simultaneous comparative studies of the broad material class, especially those with a larger diameter, with computational analyses linking toxicity to their fundamental material characteristics was lacking. It was unclear if all CNT/F confer similar toxicity, in particular, genotoxicity. Nine CNT/F (MW #1-7 and CNF #1-2), commonly found in exposure assessment studies of U.S. facilities, were evaluated with reported diameters ranging from 6 to 150 nm. All materials were extensively characterized to include distributions of physical dimensions and prevalence of bundled agglomerates. Human bronchial epithelial cells were exposed to the nine CNT/F (0-24 μg/ml) to determine cell viability, inflammation, cellular oxidative stress, micronuclei formation, and DNA double-strand breakage. Computational modeling was used to understand various permutations of physicochemical characteristics and toxicity outcomes. RESULTS: Analyses of the CNT/F physicochemical characteristics illustrate that using detailed distributions of physical dimensions provided a more consistent grouping of CNT/F compared to using particle dimension means alone. In fact, analysis of binning of nominal tube physical dimensions alone produced a similar grouping as all characterization parameters together. All materials induced epithelial cell toxicity and micronuclei formation within the dose range tested. Cellular oxidative stress, DNA double strand breaks, and micronuclei formation consistently clustered together and with larger physical CNT/F dimensions and agglomerate characteristics but were distinct from inflammatory protein changes. Larger nominal tube diameters, greater lengths, and bundled agglomerate characteristics were associated with greater severity of effect. The portion of tubes with greater nominal length and larger diameters within a sample was not the majority in number, meaning a smaller percentage of tubes with these characteristics was sufficient to increase toxicity. Many of the traditional physicochemical characteristics including surface area, density, impurities, and dustiness did not cluster with the toxicity outcomes. CONCLUSION: Distributions of physical dimensions provided more consistent grouping of CNT/F with respect to toxicity outcomes compared to means only. All CNT/F induced some level of genotoxicity in human epithelial cells. The severity of toxicity was dependent on the sample containing a proportion of tubes with greater nominal lengths and diameters.

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.

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.

Gold nanoparticles (AuNP) are largely biocompatible; however, many studies have demonstrated their potential to modulate various immune cell functions. The potential allergenicity of AuNP remains unclear despite the recognition of gold as a common contact allergen. In these studies, AuNP (29 nm) dermal sensitization potential was assessed via Local Lymph Node Assay (LLNA). Soluble gold (III) chloride (AuCl(3)) caused lymph node (LN) expansion (SI 10.9), whereas bulk particles (Au, 942 nm) and AuNP did not. Next, the pulmonary immune effects of AuNP (10, 30, 90 µg) were assessed 1, 4, and 8 days post-aspiration. All markers of lung injury and inflammation remained unaltered, but a dose-responsive increase in LN size was observed. Finally, mice were dermally-sensitized to AuCl(3) then aspirated once, twice, or three times with Au or AuNP in doses normalized for mass or surface area (SA) to assess the impact of existing contact sensitivity to gold on lung immune responses. Sensitized animals exhibited enhanced responsivity to the metal, wherein subsequent immune alterations were largely conserved with respect to dose SA. The greatest increase in bronchoalveolar lavage (BAL) lymphocyte number was observed in the high dose group - simultaneous to preferential expansion of BAL/LN CD8+ T-cells. Comparatively, the lower SA-based doses of Au/AuNP caused more modest elevations in BAL lymphocyte influx (predominantly CD4+ phenotype), exposure-dependent increases in serum IgE, and selective expansion/activation of LN CD4+ T-cells and B-cells. Overall, these findings suggest that AuNP are unlikely to cause sensitization; however, established contact sensitivity to gold may increase immune responsivity following pulmonary AuNP exposure.

Boron nitride nanotubes (BNNT) are multi-walled nanotubes composed of hexagonal B[sbnd]N bonds and possess many unique physical and chemical properties, creating a rapidly expanding market for this newly emerging nanomaterial which is still primarily in the research and development stage. The shape and high aspect ratio give rise to concern for the potential toxicity that may be associated with pulmonary exposure, especially in an occupational setting. The goal of this study was to assess lung toxicity using an in vivo time course model. The sample was manufactured to be 5 nm wide and up to 200 μm long, with ~50% purity covalently bound with hexagonal boron nitride (hBN) in the sample. Following preparation for in vivo studies, sonication of the material disrupted the longer tubes in the complex and the size distribution in dispersion medium (DM) of the structures was 13–23 nm in diameter and 0.6–1.6 μm in length. Male C57BL/6 J mice were exposed to 4 or 40 μg of BNNT or DM (vehicle control) by a single oropharyngeal aspiration. Pulmonary and systemic toxicity were investigated at 4 h, 1 d, 7 d, 1 mo and 2 mo post-exposure. Bronchoalveolar lavage (BAL) studies determined pulmonary inflammation (neutrophil influx) and cytotoxicity (lactate dehydrogenase activity) occurred at early time points and peaked at 7 d post-exposure in the high dose group. Histopathological analysis showed a minimal level of inflammatory cell infiltration in the high dose group with resolution over time and no fibrosis, and lung clearance analysis showed ~50% of the material cleared over the time course. The expression of inflammatory- and acute phase response-associated genes in the lung and liver were significantly increased by the high dose at 4 h and 1 d post-exposure. The increases in lung gene expression of Cxcl2, Ccl2, Il6, Ccl22, Ccl11, and Spp1 were significant up to 2 mo but decreased with time. The low dose exposure did not result in significant changes in any toxicological parameters measured. In summary, the BNNT-hBN sample used in this study caused acute pulmonary inflammation and injury at the higher dose, which peaked by 7 d post-exposure and showed resolution over time. Further studies are needed to determine if physicochemical properties and purity will impact the toxicity profile of BNNT and to investigate the underlying mechanisms of BNNT toxicity.

The use of colloidal silver-containing products as dietary supplements, immune boosters and surface disinfectants has increased in recent years which has elevated the potential for human exposure to silver nanoparticles and ions. Product mislabeling and long-term use of these products may put consumers at risk for adverse health outcomes including argyria. This study assessed several physical and chemical characteristics of five commercial products as well as their cytotoxicity using a rat intestinal epithelial cell (IEC-6) model. Concentrations of silver were determined for both the soluble and particulate fractions of the products. Primary particle size distribution and elemental composition were determined by transmission electron microscopy (TEM) and energy-dispersive X-ray spectroscopy (EDS), respectively. Hydrodynamic diameters were measured using nanoparticle tracking analysis (NTA) and dynamic light scattering (DLS). The effect of gastrointestinal (GI) simulation on the colloidal silver products was determined using two systems. First, physical and chemical changes of the silver nanoparticles in these products was assessed after exposure to Synthetic Stomach Fluid (SSF) resulting in particle agglomeration, and the appearance of AgCl on the surfaces and between particles. IEC-6 cells were exposed for 24 h to dilutions of the products and assessed for cell viability. The products were also treated with a three-stage simulated GI system (stomach and intestinal fluids) prior to exposure of the IEC-6 cells to the isolated silver nanoparticles. Cell viability was affected by each of the consumer products. Based on the silver nitrate and commercial silver nanoparticle dose response, the cytotoxicity for each of the colloidal silver products was attributed to the particulate silver, soluble silver or nonsilver matrix constituents.

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.

PROBLEM: As more women join the skilled-trade workforce, the effects of workplace exposures on pregnancy need to be explored. This study aims to identify the effects of mild steel and stainless steel welding fume exposures on cultured placental trophoblast cells. METHOD OF STUDY: Welding fumes (mild steel and stainless steel) were generously donated by Lincoln Electric. Electron microscopy was used to characterize welding fume particle size and the ability of particles to enter extravillous trophoblast cells (HTR-8/SVneo). Cellular viability, free radical production, cytokine production, and ability of cells to maintain invasive properties were analyzed, respectively, by WST-1, electron paramagnetic resonance, DCFH-DA, V-plex MULTI-SPOT assay system, and a matrix gel invasion assay. RESULTS: For all three welding fume types, average particle size was < 210 nm. HTR-8/SVneo cells internalized welding particles, and nuclear condensation was observed. Cellular viability was significantly decreased at the high dose of 100 microg/ml for all three welding fumes, and stainless steel generated the greatest production of the hydroxyl radical, and intracellular reactive oxygen species. Production of the cytokines IL-1beta and TNFalpha were not observed in response to welding fume exposure, but IL-6 and IL-8 were. Finally, the invasive capability of cells was decreased upon exposure to both mild steel and stainless steel welding fumes. CONCLUSION: Welding fumes are cytotoxic to extravillous trophoblasts, as is evident by the production of free radicals, pro-inflammatory cytokines, and the observed decrease in invasive capabilities.