Quantification of Free Radicals from Vaping Electronic Cigarettes Containing Nicotine Salt Solutions with Different Organic Acid Types and Concentrations.

Electronic (e-) cigarette formulations containing nicotine salts from a range of organic acid conjugates and pH values have dominated the commercial market. The acids in the nicotine salt formulations may alter the redox environment in e-cigarettes, impacting free radical formation in e-cigarette aerosol. Here, the generation of aerosol mass and free radicals from a fourth-generation e-cigarette device was evaluated at 2 wt % nicotine salts (pH 7, 30:70 mixture propylene glycol to vegetable glycerin) across eight organic acids used in e-liquids: benzoic acid (BA), salicylic acid (SLA), lactic acid (LA), levulinic acid (LVA), succinic acid (SA), malic acid (MA), tartaric acid (TA), and citric acid (CA). Furthermore, 2 wt % BA nicotine salts were studied at the following nicotine to acid ratios: 1:2 (pH 4), 1:1 (pH 7), and 2:1 (pH 8), in comparison with freebase nicotine (pH 10). Radical yields were quantified by spin-trapping and electron paramagnetic resonance (EPR) spectroscopy. The EPR spectra of free radicals in the nicotine salt aerosol matched those generated from the Fenton reaction, which are primarily hydroxyl (OH) radicals and other reactive oxygen species (ROS). Although the aerosol mass formation was not significantly different for most of the tested nicotine salts and acid concentrations, notable ROS yields were observed only from BA, CA, and TA under the study conditions. The e-liquids with SLA, LA, LVA, SA, and MA produced less ROS than the 2 wt % freebase nicotine e-liquid, suggesting that organic acids may play dual roles in the production and scavenging of ROS. For BA nicotine salts, it was found that the ROS yield increased with a higher acid concentration (or a lower nicotine to acid ratio). The observation that BA nicotine salts produce the highest ROS yield in aerosol generated from a fourth-generation vape device, which increases with acid concentration, has important implications for ROS-mediated health outcomes that may be relevant to consumers, manufacturers, and regulatory agencies.

Synthetic vitreous fibers (SVFs): adverse outcome pathways (AOPs) and considerations for next generation new approach methods (NAMs).

Fiber dimension, durability/dissolution, and biopersistence are critical factors for the risk of fibrogenesis and carcinogenesis. In the modern era, to reduce, refine, and replace animals in toxicology research, the application of in vitro test methods is paramount for hazard evaluation and designing synthetic vitreous fibers (SVFs) for safe use. The objectives of this review are to: (1) summarize the international frameworks and acceptability criteria for implementation of new approach methods (NAMs), (2) evaluate the adverse outcome pathways (AOPs), key events (KEs), and key event relationships (KERs) for fiber-induced fibrogenesis and carcinogenesis in accordance with Organization for Economic Co-operation and Development (OECD) guidelines, (3) consider existing and emerging technologies for in silico and in vitro toxicity testing for the respiratory system and the ability to predict effects in vivo, (4) outline a recommended testing strategy for evaluating the hazard and safety of novel SVFs, and (5) reflect on methods needs for in vitro in vivo correlation (IVIVC) and predictive approaches for safety assessment of new SVFs. AOP frameworks following the conceptual model of the OECD were developed through an evaluation of available molecular and cellular initiating events, which lead to KEs and KERs in the development of fiber-induced fibrogenesis and carcinogenesis. AOP framework development included consideration of fiber physicochemical properties, respiratory deposition and clearance patterns, biosolubility, and biopersistence, as well as cellular, organ, and organism responses. Available data support that fiber AOPs begin with fiber physicochemical characteristics which influence fiber exposure and biosolubility and subsequent key initiating events are dependent on fiber biopersistence and reactivity. Key cellular events of pathogenic fibers include oxidative stress, chronic inflammation, and epithelial/fibroblast proliferation and differentiation, which ultimately lead to hyperplasia, metaplasia, and fibrosis/tumor formation. Available in vitro models (e.g. single-, multi-cellular, organ system) provide promising NAMs tools to evaluate these intermediate KEs. However, data on SVFs demonstrate that in vitro biosolubility is a reasonable predictor for downstream events of in vivo biopersistence and biological effects. In vitro SVF fiber dissolution rates >100 ng/cm2/hr (glass fibers in pH 7 and stone fibers in pH 4.5) and in vivo SVF fiber clearance half-life less than 40 or 50 days were not associated with fibrosis or tumors in animals. Long (fiber lengths >20 µm) biodurable and biopersistent fibers exceeding these fiber dissolution and clearance thresholds may pose a risk of fibrosis and cancer. In vitro fiber dissolution assays provide a promising avenue and potentially powerful tool to predict in vivo SVF fiber biopersistence, hazard, and health risk. NAMs for fibers (including SVFs) may involve a multi-factor in vitro approach leveraging in vitro dissolution data in complement with cellular- and tissue- based in vitro assays to predict health risk.

Carbonyls and Aerosol Mass Generation from Vaping Nicotine Salt Solutions Using Fourth- and Third-Generation E-Cigarette Devices: Effects of Coil Resistance, Coil Age, and Coil Metal Material.

Aerosol formation and production yields from 11 carbonyls (carbonyl concentration per aerosol mass unit) were investigated (1) from a fourth-generation (4th gen) e-cigarette device at different coil resistances and coil age (0-5000 puffs) using unflavored e-liquid with 2% benzoic acid nicotine salt, (2) between a sub-ohm third-generation (3rd gen) tank mod at 0.12 Ω and a 4th gen pod at 1.2 Ω using e-liquid with nicotine salt, together with nicotine yield, and (3) from 3rd gen coils of different metals (stainless steel, kanthal, nichrome) using e-liquid with freebase nicotine. Coil resistance had an inverse relationship with coil temperature, and coil temperature was directly proportional to aerosol mass formation. Trends in carbonyl yields depended on carbonyl formation mechanisms. Carbonyls produced primarily from thermal degradation chemistry (e.g., formaldehyde, acetaldehyde, acrolein, propionaldehyde) increased per aerosol mass with higher coil resistances, despite lower coil temperature. Carbonyls produced primarily from chemistry initiated by reactive oxygen species (ROS) (e.g., hydroxyacetone, dihydroxyacetone, methylglyoxal, glycolaldehyde, lactaldehyde) showed the opposite trend. Coil age did not alter coil temperature nor aerosol mass formation but had a significant effect on carbonyl formation. Thermal carbonyls were formed optimally at 500 puffs in our study and then declined to a baseline, whereas ROS-derived carbonyls showed a slow rise to a maximum trend with coil aging. The 3rd gen versus 4th gen device comparison mirrored the trends in coil resistance. Nicotine yields per aerosol mass were consistent between 3rd and 4th gen devices. Coil material did not significantly alter aerosol formation nor carbonyl yield when adjusted for wattage. This work shows that sub-ohm coils may not necessarily produce higher carbonyl yields even when they produce more aerosol mass. Furthermore, carbonyl formation is dynamic and not generalizable during the coil's lifetime. Finally, studies that compare data across different e-cigarette devices, coil age, and coil anatomy should account for the aerosol chemistry trends that depend on these parameters.

Fiber biodurability and biopersistence: historical toxicological perspective of synthetic vitreous fibers (SVFs), the long fiber paradigm, and implications for advanced materials.

Extensive toxicology studies of synthetic vitreous fibers (SVFs) demonstrated that fiber dimension, durability/dissolution, and biopersistence are critical factors for risk of fibrogenesis and carcinogenesis. Lessons learned from the SVF experience provide useful context for predicting hazards and risk of nano-enabled advanced materials. This review provides (1) a historical toxicological overview of animal and in vitro toxicology studies of SVFs, (2) key findings that long durable fibers pose a risk of fibrogenic and tumorigenic responses and not short fibers or long soluble fibers, (3) in vitro and in vivo test methods for biodurability and biopersistence and associated predictive thresholds for fibrosis or tumors, and (4) recommendations for testing of advanced materials. Generally, SVFs (fiber lengths >20 µm) with in vitro fiber dissolution rates greater than 100 ng/cm2/hr (glass fibers in pH 7 and stone fibers in pH 4.5) and in vivo fiber clearance less than WT1/2 40 or 50 days were not associated with fibrosis or tumors. Long biodurable and biopersistent fibers exceeding these fiber dissolution and clearance thresholds may pose a risk of fibrosis and cancer. Fiber length-, durability-, and biopersistent-dependent factors that influence pathogenicity of mineral fibers are also expected to affect the biological effects of high aspect ratio nanomaterials (HARN). Only with studies aimed to correlate in vitro durability, in vivo biopersistence, and biological outcomes will it be determined whether similar or different in vitro fiber dissolution and in vivo half-life thresholds, which exempt carcinogenicity classification of SVFs, can also apply to HARNs.

Impact of e-Liquid Composition, Coil Temperature, and Puff Topography on the Aerosol Chemistry of Electronic Cigarettes.

E-cigarette aerosol is a complex mixture of gases and particles with a composition that is dependent on the e-liquid formulation, puffing regimen, and device operational parameters. This work investigated mainstream aerosols from a third generation device, as a function of coil temperature (315-510 °F, or 157-266 °C), puff duration (2-4 s), and the ratio of propylene glycol (PG) to vegetable glycerin (VG) in e-liquid (100:0-0:100). Targeted and untargeted analyses using liquid chromatography high-resolution mass spectrometry, gas chromatography, in situ chemical ionization mass spectrometry, and gravimetry were used for chemical characterizations. PG and VG were found to be the major constituents (>99%) in both phases of the aerosol. Most e-cigarette components were observed to be volatile or semivolatile under the conditions tested. PG was found almost entirely in the gas phase, while VG had a sizable particle component. Nicotine was only observed in the particle phase. The production of aerosol mass and carbonyl degradation products dramatically increased with higher coil temperature and puff duration, but decreased with increasing VG fraction in the e-liquid. An exception is acrolein, which increased with increasing VG. The formation of carbonyls was dominated by the heat-induced dehydration mechanism in the temperature range studied, yet radical reactions also played an important role. The findings from this study identified open questions regarding both pathways. The vaping process consumed PG significantly faster than VG under all tested conditions, suggesting that e-liquids become more enriched in VG and the exposure to acrolein significantly increases as vaping continues. It can be estimated that a 30:70 initial ratio of PG:VG in the e-liquid becomes almost entirely VG when 60-70% of e-liquid remains during the vaping process at 375 °F (191 °C). This work underscores the need for further research on the puffing lifecycle of e-cigarettes.

Application of High-Resolution Mass Spectrometry and a Theoretical Model to the Quantification of Multifunctional Carbonyls and Organic Acids in e-Cigarette Aerosol.

Electronic (e-) cigarette aerosol (particle and gas) is a complex mixture of chemicals, of which the profile is highly dependent on device operating parameters and e-liquid flavor formulation. The thermal degradation of the e-liquid solvents propylene glycol and glycerol often generates multifunctional carbonyls that are challenging to quantify because of unavailability of standards. We developed a theoretical method to calculate the relative electrospray ionization sensitivities of hydrazones of organic acids and carbonyls with 2,4-dinitrophenylhydrazine based on their gas-phase basicities (ΔGdeprotonation). This method enabled quantification by high-performance liquid chromatography-high-resolution mass spectrometry HPLC-HRMS in the absence of chemical standards. Accurate mass and tandem multistage MS (MSn) were used for structure identification of vaping products. We quantified five simple carbonyls, six hydroxycarbonyls, four dicarbonyls, three acids, and one phenolic carbonyl in the e-cigarette aerosol with Classic Tobacco flavor. Our results suggest that hydroxycarbonyls, such as hydroxyacetone, lactaldehyde, and dihydroxyacetone can be significant components in e-cigarette aerosols but have received less attention in the literature and have poorly understood health effects. The data support the radical-mediated e-liquid thermal degradation scheme that has been previously proposed and emphasize the need for more research on the chemistry and toxicology of the complex product formation in e-cigarette aerosols.

PBPK modeling characterization of potential acute impairment effects from inhalation of ethanol during e-cigarette use.

Objective: Ethanol is used as a solvent for flavoring chemicals in some electronic cigarette (e-cigarette) liquids (e-liquids). However, there are limited data available regarding the effects of inhalation of ethanol on blood alcohol concentration (BAC) during e-cigarette use. In this study, a modified physiologically based pharmacokinetic (PBPK) model for inhalation of ethanol was used to estimate the BAC time-profile of e-cigarette users who puffed an e-liquid containing 23.5% ethanol. Materials and Methods: A modified PBPK model for inhalation of ethanol was developed. Use characteristics were estimated based on first-generation and second-generation e-cigarette topography parameters. Three representative use-case puffing profiles were modeled: a user that took many, short puffs; a typical user with intermediate puff counts and puff durations; and a user that took fewer, long puffs. Results and Discussion: The estimated peak BACs for these three user profiles were 0.22, 0.22, and 0.30 mg/L for first-generation devices, respectively, and 0.85, 0.58, and 0.34 mg/L for second-generation devices, respectively. Additionally, peak BACs for individual first-generation users with directly measured puffing parameters were estimated to range from 0.06 to 0.67 mg/L. None of the scenarios modeled predicted a peak BAC result that approached toxicological or regulatory thresholds that would be associated with physiological impairment (roughly 0.01% or 100 mg/L). Conclusions: The approach used in this study, combining a validated PBPK model for a toxicant with peer-reviewed topographical parameters, can serve as a screening-level exposure assessment useful for evaluation of the safety of e-liquid formulations. Abbreviations: BAC: blood alcohol concentration; e-cigarette: electronic cigarette; e-liquid: e-cigarette liquid or propylene glycol and/or vegetable glycerin-based liquid; HS-GC-FID: headspace gas chromatography with flame-ionization detection; HS-GC-MS: headspace gas chromatography-mass spectrometry; PBPK: physiologically based pharmacokinetic; Cair: puff concentration expressed as ppm; Cair,mass: ethanol air concentration expressed on a mass basis; Cv: ethanol concentration in the venous blood; ρ: density; EC: ethanol concentration in the liquid; PLC: liquid consumption per puff; PAV: air volume of the puff; Cair,mass: puff concentration expressed as ppm; MW: molecular weight; P: pressure; T: temperature; PK: pharmacokinetic.

Nanoparticles, lung injury, and the role of oxidant stress.

The emergence of engineered nanoscale materials has provided significant advancements in electronic, biomedical, and material science applications. Both engineered nanoparticles and nanoparticles derived from combustion or incidental processes exhibit a range of physical and chemical properties that induce inflammation and oxidative stress in biological systems. Oxidative stress reflects the imbalance between the generation of reactive oxygen species and the biochemical mechanisms to detoxify and repair the damage resulting from reactive intermediates. This review examines current research on incidental and engineered nanoparticles in terms of their health effects on lungs and the mechanisms by which oxidative stress via physicochemical characteristics influences toxicity or biocompatibility. Although oxidative stress has generally been thought of as an adverse biological outcome, this review also briefly discusses some of the potential emerging technologies to use nanoparticle-induced oxidative stress to treat disease in a site-specific fashion.

Analysis of workplace compliance measurements of asbestos by the U.S. Occupational Safety and Health Administration (1984-2011).

The United States Occupational Safety and Health Administration (OSHA) maintains the Chemical Exposure Health Data (CEHD) and the Integrated Management Information System (IMIS) databases, which contain quantitative and qualitative data resulting from compliance inspections conducted from 1984 to 2011. This analysis aimed to evaluate trends in workplace asbestos concentrations over time and across industries by combining the samples from these two databases. From 1984 to 2011, personal air samples ranged from 0.001 to 175 f/cc. Asbestos compliance sampling data associated with the construction, automotive repair, manufacturing, and chemical/petroleum/rubber industries included measurements in excess of 10 f/cc, and were above the permissible exposure limit from 2001 to 2011. The utility of combining the databases was limited by the completeness and accuracy of the data recorded. In this analysis, 40% of the data overlapped between the two databases. Other limitations included sampling bias associated with compliance sampling and errors occurring from user-entered data. A clear decreasing trend in both airborne fiber concentrations and the numbers of asbestos samples collected parallels historically decreasing trends in the consumption of asbestos, and declining mesothelioma incidence rates. Although air sampling data indicated that airborne fiber exposure potential was high (>10 f/cc for short and long-term samples) in some industries (e.g., construction, manufacturing), airborne concentrations have significantly declined over the past 30 years. Recommendations for improving the existing exposure OSHA databases are provided.

Airborne asbestos exposures associated with gasket and packing replacement: a simulation study of flange and valve repair work and an assessment of exposure variables.

A simulation study was conducted to evaluate worker and area exposure to airborne asbestos associated with the replacement of asbestos-containing gaskets and packing materials from flanges and valves and assess the influence of several variables previously not investigated. Additionally, potential of take home exposures from clothing worn during the study was characterized. Our data showed that product type, ventilation type, gasket location, flange or bonnet size, number of flanges involved, surface characteristics, gasket surface adherence, and even activity type did not have a significant effect on worker exposures. Average worker asbestos exposures during flange gasket work (PCME=0.166 f/cc, 12-59 min) were similar to average worker asbestos exposures during valve overhaul work (PCME=0.165 f/cc, 7-76 min). Average 8-h TWA asbestos exposures were estimated to range from 0.010 to 0.062 f/cc. Handling clothes worn during gasket and packing replacement activities demonstrated exposures that were 0.71% (0.0009 f/cc 40-h TWA) of the airborne asbestos concentration experienced during the 5 days of the study. Despite the many variables considered in this study, exposures during gasket and packing replacement occur within a relatively narrow range, are below current and historical occupational exposure limits for asbestos, and are consistent with previously published data.

Toxicology of wear particles of cobalt-chromium alloy metal-on-metal hip implants Part II: Importance of physicochemical properties and dose in animal and in vitro studies as a basis for risk assessment.

The objective of the Part II analysis was to evaluate animal and in vitro toxicology studies of CoCr particles with respect to their physicochemistry and dose relevance to metal-on-metal (MoM) implant patients as derived from Part I. In the various toxicology studies, physicochemical characteristics were infrequently considered and administered doses were orders of magnitude higher than what occurs in patients. Co was consistently shown to rapidly release from CoCr particles for distribution and elimination from the body. CoCr micron sized particles appear more biopersistent in vivo resulting in inflammatory responses that are not seen with similar mass concentrations of nanoparticles. We conclude, that in an attempt to obtain data for a complete risk assessment, future studies need to focus on physicochemical characteristics of nano and micron sized particles and on doses and dose metrics relevant to those generated in patients or in properly conducted hip simulator studies.

Toxicology of wear particles of cobalt-chromium alloy metal-on-metal hip implants Part I: physicochemical properties in patient and simulator studies.

The objective of Part I of this analysis was to identify the relevant physicochemical characteristics of wear particles from cobalt-chromium alloy (CoCr) metal-on-metal (MoM) hip implant patients and simulator systems. For well-functioning MoM hip implants, the volumetric wear rate is low (<1mm(3) per million cycles or per year) and the majority of the wear debris is composed of oxidized Cr nanoparticles (<100nm) with minimal or no Co content. For implants with surgical malpositioning, the volumetric wear rate is as high as 100mm(3) per million cycles or per year and the size distribution of wear debris can be skewed to larger sizes (up to 1000nm) and contain higher concentrations of Co. In order to obtain data suitable for a risk assessment of wear debris in MoM hip implant patients, future studies need to focus on particle characteristics relevant to those generated in patients or in properly conducted simulator studies. FROM THE CLINICAL EDITOR: Metallic implants are very common in the field of orthopedics. Nonetheless, concerns have been raised about the implications of nano-sized particles generated from the wear of these implants. In this two-part review, the authors first attempted to identify and critically evaluate the relevant physicochemical characteristics of CoCr wear particles from hip implant patients and simulator systems. Then they evaluated in vitro and animal toxicology studies with respect to the physicochemistry and dose-relevance to metal-on-metal implant patients.

Evaluation of the California Safer Consumer Products Regulation and the impact on consumers and product manufacturers.

Chemistry enables more than 95% of products in the marketplace. Over the past 20 years, various entities began to generate inventories of chemicals ("chemical watch lists") potentially associated with human or environmental health risks. Some lists included thousands of chemicals, while others listed only a few chemistries with limited properties or toxicological endpoints (e.g., neurotoxicants). Enacted on October 1, 2013, the California Safer Consumer Products Regulation (SCP) utilized data from chemical inventory lists to create one master list. This paper aims to discuss the background and requirements of this regulation. Additionally, we wanted to understand the universe of Candidate Chemicals identified by the Regulation. Data from all 23 chemical lists identified in the SCP Regulation were entered into a database. The most prevalent chemicals among the ∼2900 chemicals are identified, including the most prevalent chemical, lead, appearing on 65% of lists, followed by DEHP (52%), perchloroethylene (48%), and benzene (48%). Our results indicated that the most prevalent Candidate Chemicals were either persistent, bioaccumulative, carcinogenic, or reprotoxic. This regulation will have wide-ranging impact in California and throughout the global supply chain, which is highlighted through selected examples and case studies.

Airborne asbestos exposures associated with gasket and packing replacement: a simulation study and meta-analysis.

Exposures to airborne asbestos during the removal and installation of internal gaskets and packing associated with a valve overhaul were characterized and compared to published data according to different variables (e.g., product, equipment, task, tool, setting, duration). Personal breathing zone and area samples were collected during twelve events simulating gasket and packing replacement, clean-up and clothing handling. These samples were analyzed using PCM and TEM methods and PCM-equivalent (PCME) airborne asbestos concentrations were calculated. A meta-analysis was performed to compare these data with airborne asbestos concentrations measured in other studies involving gaskets and packing. Short-term mechanic and assistant airborne asbestos concentrations during valve work averaged 0.013f/cc and 0.008f/cc (PCME), respectively. Area samples averaged 0.008f/cc, 0.005f/cc, and 0.003f/cc (PCME) for center, bystander, and remote background, respectively. Assuming a tradesman conservatively performs 1-3 gasket and/or packing replacements daily, an average 8-h TWA was estimated to be 0.002-0.010f/cc (PCME). Combining these results in a meta-analysis of the published exposure data showed that the majority of airborne asbestos exposures during work with gaskets and packing fall within a consistent and low range. Significant differences in airborne concentrations were observed between power versus manual tools and removal versus installation tasks. Airborne asbestos concentrations resulting from gasket and packing work during a valve overhaul are consistent with historical exposure data on replacement of asbestos-containing gasket and packing materials involving multiple variables and, in nearly all plausible scenarios, result in average airborne asbestos concentrations below contemporaneous occupational exposure limits for asbestos.

Slovakian glass fibre factory genotoxicity biomonitoring study - unsupported adverse outcome pathway (AOP) from the toxicology and human epidemiological experience of synthetic vitreous fibres (SVFs).

The article by Ceppi and colleagues, Genotoxic Effects of Occupational Exposure to, Glass Fibres - A Human Biomonitoring Study, published in Mutation Research -Genetic Toxicology and Environmental Mutagenesis in 2023 was reviewed with great interest. The authors undertook a novel approach to conducting a biomonitoring study of genotoxicity markers among a population of glass fibre manufacturing workers in Slovakia. On the surface, the Ceppi et al. (2023) study provides an interesting application of genotoxicity markers among a human population of workers to explore potential markers of effect (DNA strand breaks) and potential risk of susceptibility (e.g., genetic damage, disease, death). However, limited data for exposure reconstruction, uncertain influences from smoking history, and lack of consideration of decades of human epidemiology research showing no increased risk of malignant or non-malignant respiratory disease and mortality among glass fibre manufacturing workers, reveals that the conclusions of the authors are overreaching and inconsistent with the existing science. The limitations of this study preclude the ability to draw causal inferences or conclusions about DNA strand breaks as a marker of exposure, effect, or susceptibility within this population of Slovakian glass fibre workers. Further longitudinal research is required (e.g., more robust temporal assessment of occupational exposures - fibres and other compounds - and smoking history) to support the study conclusions.

Considerations for the development of health-based surface dust cleanup criteria for beryllium.

The exposure-response patterns with beryllium sensitization (BeS), chronic beryllium disease (CBD) and lung cancer are influenced by a number of biological and physicochemical factors. Recent studies have suggested dermal exposure as a pathway for BeS. In light of the current non-health-based DOE Beryllium Rule surface criteria, the feasibility of deriving a human health-based surface dust cleanup criteria (SDCC) for beryllium was assessed based on toxicology and health risk factors via all potential routes of exposure. Beryllium-specific and general exposure factors were evaluated, including (1) beryllium physicochemical characteristics, bioavailability and influence on disease prevalence, and (2) chemical dissipation, resuspension and transfer. SDCC for non-cancer (SDCC) and cancer (SDCC) endpoints were derived from a combination of modern methods applied for occupational, residential and building reentry surface dust criteria. The most conservative SDCC estimates were derived for dermal exposure (5-379 µg/100 cm for 0.1-1% damaged skin and 17-3337 µg/100 cm for intact skin), whereas the SDCC for inhalation exposure ranged from 51 to 485 µg/100 cm. Considering this analysis, the lowest DOE surface criterion of 0.2 µg/100 cm is conservative for minimizing exposure and potential risks associated with beryllium-contaminated surfaces released for non-beryllium industrial or public sector use. Although methodological challenges exist with sampling and analysis procedures, data variability and interpretation of surface dust information in relation to anthropogenic and natural background concentrations, this evaluation should provide useful guidance with regard to cleanup of manufacturing equipment or remediation of property for transfer to the general public or non-beryllium industrial facilities.

Review and Evaluation of the Potential Health Effects of Oxidic Nickel Nanoparticles.

The exceptional physical and chemical properties of nickel nanomaterials have been exploited in a range of applications such as electrical conductors, batteries, and biomaterials. However, it has been suggested that these unique properties may allow for increased bioavailability, bio-reactivity, and potential adverse health effects. Thus, the purpose of this review was to critically evaluate data regarding the toxicity of oxidic nickel nanoparticles (nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) nanoparticles) with respect to: (1) physico-chemistry properties; (2) nanomaterial characterization in the defined delivery media; (3) appropriateness of model system and translation to potential human effects; (4) biodistribution, retention, and clearance; (5) routes and relevance of exposure; and (6) current research data gaps and likely directions of future research. Inhalation studies were prioritized for review as this represents a potential exposure route in humans. Oxidic nickel particle size ranged from 5 to 100 nm in the 60 studies that were identified. Inflammatory responses induced by exposure of oxidic nickel nanoparticles via inhalation in rodent studies was characterized as acute in nature and only displayed chronic effects after relatively large (high concentration and long duration) exposures. Furthermore, there is no evidence, thus far, to suggest that the effects induced by oxidic nickel nanoparticles are related to preneoplastic events. There are some data to suggest that nano- and micron-sized NiO particles follow a similar dose response when normalized to surface area. However, future experiments need to be conducted to better characterize the exposure-dose-response relationship according to specific surface area and reactivity as a dose metric, which drives particle dissolution and potential biological responses.

Health effects of inhaled engineered and incidental nanoparticles.

Engineered nanoscale materials provide tremendous promise for technological advancements; however, concerns have been raised about whether research of the possible health risks of these nanomaterials is keeping pace with products going to market. Research on nanomaterials, including carbon nanotubes, semiconductor crystals, and other ultrafine particles (i.e., titanium dioxide, quantum dots, iridium) will be examined to illustrate what is currently known or unknown about how particle characteristics (e.g., size, agglomeration, morphology, solubility, surface chemistry) and exposure/dose metrics (e.g., mass, size, surface area) influence the biological fate and toxicity of inhaled nanosized particles. The fact that nanosized particles (1) have a potentially high efficiency for deposition; (2) target both the upper and lower regions of the respiratory tract; (3) are retained in the lungs for a long period of time, and (4) induce more oxidative stress and cause greater inflammatory effects than their fine-sized equivalents suggest a need to study the impact of these particles on the body. Achieving a better understanding of the dynamics at play between particle physicochemistry, transport patterns, and cellular responses in the lungs and other organs will provide a future basis for establishing predictive measures of toxicity or biocompatibility and a framework for assessing potential human health risks.

Respiratory Health Effects of Exposure to Ambient Particulate Matter and Bioaerosols.

Researchers have been studying the respiratory health effects of ambient air pollution for more than 70 years. While air pollution as a whole can include gaseous, solid, and liquid constituents, this article focuses only on the solid and liquid fractions, termed particulate matter (PM). Although PM may contain anthropogenic, geogenic, and/or biogenic fractions, in this article, particles that originate from microbial, fungal, animal, or plant sources are distinguished from PM as bioaerosols. Many advances have been made toward understanding which particle and exposure characteristics most influence deposition and clearance processes in the respiratory tract. These characteristics include particle size, shape, charge, and composition as well as the exposure concentration and dose rate. Exposure to particles has been directly associated with the exacerbation and, under certain circumstances, onset of respiratory disease. The circumstances of exposure leading to disease are dependent on stressors such as human activity level and changing particle composition in the environment. Historically, researchers assumed that bioaerosols were too large to be inhaled into the deep lung, and thus, not applicable for study in conjunction with PM2.5 (the 2.5-µm and below size fraction that can reach the deep lung); however, this concept is beginning to be challenged. While there is extensive research on the health effects of PM and bioaerosols independent of each other, only limited work has been performed on their coexposure. Studying these two particle types as dual stressors to the respiratory system may aid in more thoroughly understanding the etiology of respiratory injury and disease. © 2020 American Physiological Society. Compr Physiol 10:1-20, 2020.