Last data update: Jun 17, 2024. (Total: 47034 publications since 2009)
Records 1-8 (of 8 Records) |
Query Trace: Badding MA [original query] |
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Application of the ICRP respiratory tract model to estimate pulmonary retention of industrially sampled indium-containing dusts
Stefaniak AB , Virji MA , Badding MA , Cummings KJ . Inhal Toxicol 2017 29 (4) 1-10 Inhalation of indium-containing dusts is associated with the development of indium lung disease. Workers may be exposed to several different chemical forms of indium; however, their lung dosimetry is not fully understood. We characterized the physicochemical properties and measured the lung dissolution kinetics of eight indium-containing dusts. Indium dissolution rates in artificial lung fluids spanned two orders of magnitude. We used the International Commission on Radiological Protection (ICRP) human respiratory model (HRTM) to estimate pulmonary indium deposition, retention and biokinetic clearance to blood. For a two-year (median workforce tenure at facility) exposure to respirable-sized particles of the indium materials, modeled indium clearance (>99.99% removed) from the alveolar-interstitial compartment was slow for all dusts; salts would clear in 4 years, sintered indium-tin oxide (ITO) would clear in 9 years, and indium oxide would require 48 years. For this scenario, the ICRP HRTM predicted that indium translocated to blood would be present in that compartment for 3.5-18 years after cessation of exposure, depending on the chemical form. For a 40-year exposure (working lifetime), clearance from the alveolar-interstitial compartment would require 5, 10 and 60 years for indium salts, sintered ITO and indium oxide, respectively and indium would be present in blood for 5-53 years after exposure. Consideration of differences in chemical forms of indium, dissolution rates, alveolar clearance and residence time in blood should be included in exposure assessment and epidemiological studies that rely on measures of total indium in air or blood to derive risk estimates. |
Evaluation of the effect of valence state on cerium oxide nanoparticle toxicity following intratracheal instillation in rats
Dunnick KM , Morris AM , Badding MA , Barger M , Stefaniak AB , Sabolsky EM , Leonard SS . Nanotoxicology 2016 10 (7) 1-34 Cerium (Ce) is becoming a popular metal for use in electrochemical applications. When in the form of cerium oxide (CeO2), Ce can exist in both a 3+ and 4+ valence state, acting as an ideal catalyst. Previous in vitro and in vivo evidence have demonstrated that CeO2 has either anti- or pro-oxidant properties, possibly due to the ability of the nanoparticles to transition between valence states. Therefore, we chose to chemically modify the nanoparticles to shift the valence state toward 3+. During the hydrothermal synthesis process, 10 mol% gadolinium (Gd) and 20 mol% Gd, was substituted into the lattice of the CeO2 nanoparticles forming a perfect solid solution with various A-site valence states. These two Gd-doped CeO2 nanoparticles were compared to pure CeO2 nanoparticles. Preliminary characteristics indicated that doping results in minimal size and zeta potential changes but alters valence state. Following characterization, male Sprague-Dawley rats were exposed to 0.5 or 1.0 mg/kg nanoparticles via a single intratracheal instillation. Animals were sacrificed and bronchoalveolar lavage fluid and various tissues were collected to determine the effect of valence state and oxygen vacancies on toxicity 1, 7, or 84 days post-exposure. Results indicate that damage, as measured by elevations in lactate dehydrogenase, occurred within 1 day post-exposure and was sustained 7 days post-exposure, but subsided to control levels 84 days post-exposure. Further, no inflammatory signaling or lipid peroxidation occurred following exposure with any of the nanoparticles. Our results implicate that valence state has a minimal effect on CeO2 nanoparticle toxicity in vivo. |
Pulmonary toxicity of indium-tin oxide production facility particles in rats
Badding MA , Fix NR , Orandle MS , Barger MW , Dunnick KM , Cummings KJ , Leonard SS . J Appl Toxicol 2015 36 (4) 618-26 Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Occupational exposures to potentially toxic particles generated during ITO production have increased in recent years as the demand for consumer electronics continues to rise. Previous studies have demonstrated cytotoxicity in vitro and animal models have shown pulmonary inflammation and injury in response to various indium-containing particles. In humans, pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which indium materials or specific processes in the workplace may be the most toxic to workers is unknown. Here we examined the pulmonary toxicity of three different particle samples that represent real-life worker exposures, as they were collected at various production stages throughout an ITO facility. Indium oxide (In2 O3 ), sintered ITO (SITO) and ventilation dust (VD) particles each caused pulmonary inflammation and damage in rats over a time course (1, 7 and 90 days post-intratracheal instillation), but SITO and VD appeared to induce greater toxicity in rat lungs than In2 O3 at a dose of 1 mg per rat. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days after treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of an emerging occupational health issue. |
Sintered indium-tin oxide particles induce pro-inflammatory responses in vitro, in part through inflammasome activation
Badding MA , Schwegler-Berry D , Park JH , Fix NR , Cummings KJ , Leonard SS . PLoS One 2015 10 (4) e0124368 Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does the concern for occupational exposures to particles containing these potentially toxic metal oxides. Indium-containing particles have been shown to be cytotoxic in cultured cells and pro-inflammatory in pulmonary animal models. In humans, pulmonary alveolar proteinosis and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which ITO production materials may be the most toxic to workers and how they initiate pulmonary inflammation remain poorly understood. Here we examined four different particle samples collected from an ITO production facility for their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered ITO (SITO), and ventilation dust particles activated nuclear factor kappa B (NFkappaB) within 3 h of treatment. However, only SITO induced robust cytokine production (IL-1beta, IL-6, TNFalpha, and IL-8) within 24 h in both RAW 264.7 mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and others have previously demonstrated SITO-induced cytotoxicity as well. These findings suggest that SITO particles activate the NLRP3 inflammasome, which has been implicated in several immune-mediated diseases via its ability to induce IL-1beta release and cause subsequent cell death. Inflammasome activation by SITO was confirmed, but it required the presence of endotoxin. Further, a phagocytosis assay revealed that pre-uptake of SITO or ventilation dust impaired proper macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory responses to SITO particles by both macrophage and epithelial cells may initiate and propagate indium lung disease. These findings will provide a better understanding of the molecular mechanisms behind an emerging occupational health issue. |
Evaluation of the pulmonary toxicity of a fume generated from a nickel-, copper-based electrode to be used as a substitute in stainless steel welding
Antonini JM , Badding MA , Meighan TG , Keane M , Leonard SS , Roberts JR . Environ Health Insights 2014 8 11-20 Epidemiology has indicated a possible increase in lung cancer among stainless steel welders. Chromium (Cr) is a primary component of stainless steel welding fume. There is an initiative to develop alternative welding consumables [nickel (Ni)- and copper (Cu)-based alloys] that do not contain Cr. No study has been performed to evaluate the toxicity of fumes generated from Ni- and Cu-based consumables. Dose–response and time-course effects on lung toxicity of a Ni- and Cu-based welding fume (Ni–Cu WF) were examined using an in vivo and in vitro bioassay, and compared with two other well-characterized welding fumes. Even though only trace amounts of Cr were present, a persistent increase in lung injury and inflammation was observed for the Ni–Cu WF compared to the other fumes. The difference in response appears to be due to a direct cytotoxic effect by the Ni–Cu WF sample on lung macrophages as opposed to an elevated production of reactive oxygen species (ROS). |
Cytotoxicity and characterization of particles collected from an indium-tin oxide production facility
Badding MA , Stefaniak AB , Fix NR , Cummings KJ , Leonard SS . J Toxicol Environ Health A 2014 77 (20) 1193-209 Occupational exposure to indium compound particles has recently been associated with lung disease among workers in the indium-tin oxide (ITO) industry. Previous studies suggested that excessive alveolar surfactant and reactive oxygen species (ROS) may play a role in the development of pulmonary lesions following exposure to indium compounds. However, toxicity at the cellular level has not been comprehensively evaluated. Thus, the aim of this study was to assess which, if any, compounds encountered during ITO production are toxic to cultured cells and ultimately contribute to the pathogenesis of indium lung disease. The compounds used in this study were collected from eight different processing stages at an ITO production facility. Enhanced dark field imaging showed 5 of the compounds significantly associated with cells within 1 h, suggesting that cellular reactions to the compound particles may be occurring rapidly. To examine the potential cytotoxic effects of these associations, ROS generation, cell viability, and apoptosis were evaluated following exposures in RAW 264.7 mouse monocyte macrophage and BEAS-2B human bronchial epithelial cell lines. Both exhibited reduced viability with exposures, while apoptosis only occurred in RAW 264.7 cells. Our results suggested that excessive ROS production is likely not the predominant mechanism underlying indium-induced lung disease. However, the effects on cell viability reveal that several of the compounds are cytotoxic, and therefore, exposures need to be carefully monitored in the industrial setting. |
The effect of tungstate nanoparticles on reactive oxygen species and cytotoxicity in raw 264.7 mouse monocyte macrophage cells
Dunnick KM , Badding MA , Schwegler-Berry D , Patete JM , Koenigsmann C , Wong SS , Leonard SS . J Toxicol Environ Health A 2014 77 (20) 1251-68 Due to their unique size, surface area, and chemical characteristics, nanoparticles' use in consumer products has increased. However, the toxicity of nanoparticle (NP) exposure during the manufacturing process has not been fully assessed. Tungstate NP are used in numerous products, including but not limited to scintillator detectors and fluorescent lighting. As with many NP, no apparent toxicity studies have been completed with tungstate NP. The hypothesis that tungstate NP in vitro exposure results in reactive oxygen species (ROS) formation and cytotoxicity was examined. Differences in toxicity based on tungstate NP size, shape (sphere vs. wire), and chemical characteristics were determined. RAW 264.7 mouse monocyte macrophages were exposed to tungstate NP, and ROS formation was assessed via electron spin resonance (ESR), and several assays including hydrogen peroxide, intracellular ROS, and Comet. Results showed ROS production induced by tungstate nanowire exposure, but this exposure did not result in oxidative DNA damage. Nanospheres showed neither ROS nor DNA damage following cellular exposure. Cells were exposed over 72 h to assess cytotoxicity using an MTT (tetrazolium compound) assay. Results showed that differences in cell death between wires and spheres occurred at 24 h but were minimal at both 48 and 72 h. The present results indicate that tungstate nanowires are more reactive and produce cell death within 24 h of exposure, whereas nanospheres are less reactive and did not produce cell death. Results suggest that differences in shape may affect reactivity. However, regardless of the differences in reactivity, in general both shapes produced mild ROS and resulted in minimal cell death at 48 and 72 h in RAW 264.7 cells. |
A comparison of cytotoxicity and oxidative stress from welding fumes generated with a new nickel-, copper-based consumable versus mild and stainless steel-based welding in RAW 264.7 mouse macrophages
Badding MA , Fix NR , Antonini JM , Leonard SS . PLoS One 2014 9 (6) e101310 Welding processes that generate fumes containing toxic metals, such as hexavalent chromium (Cr(VI)), manganese (Mn), and nickel (Ni), have been implicated in lung injury, inflammation, and lung tumor promotion in animal models. While federal regulations have reduced permissible worker exposure limits to Cr(VI), this is not always practical considering that welders may work in confined spaces and exhaust ventilation may be ineffective. Thus, there has been a recent initiative to minimize the potentially hazardous components in welding materials by developing new consumables containing much less Cr(VI) and Mn. A new nickel (Ni) and copper (Cu)-based material (Ni-Cu WF) is being suggested as a safer alternative to stainless steel consumables; however, its adverse cellular effects have not been studied. This study compared the cytotoxic effects of the newly developed Ni-Cu WF with two well-characterized welding fumes, collected from gas metal arc welding using mild steel (GMA-MS) or stainless steel (GMA-SS) electrodes. RAW 264.7 mouse macrophages were exposed to the three welding fumes at two doses (50 microg/ml and 250 microg/ml) for up to 24 hours. Cell viability, reactive oxygen species (ROS) production, phagocytic function, and cytokine production were examined. The GMA-MS and GMA-SS samples were found to be more reactive in terms of ROS production compared to the Ni-Cu WF. However, the fumes from this new material were more cytotoxic, inducing cell death and mitochondrial dysfunction at a lower dose. Additionally, pre-treatment with Ni-Cu WF particles impaired the ability of cells to phagocytize E. coli, suggesting macrophage dysfunction. Thus, the toxic cellular responses to welding fumes are largely due to the metal composition. The results also suggest that reducing Cr(VI) and Mn in the generated fume by increasing the concentration of other metals (e.g., Ni, Cu) may not necessarily improve welder safety. |
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