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James M Antonini - One of the best experts on this subject based on the ideXlab platform.
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influence of Welding Fume metal composition on lung toxicity and tumor formation in experimental animal models
Journal of Occupational and Environmental Hygiene, 2019Co-Authors: Patti C Zeidlererdely, Lauryn M Falcone, James M AntoniniAbstract:Millions of workers in the US and worldwide are exposed to complex, metal-rich Welding Fumes. Although Welding is a crucial industrial process, the generated Fumes are known to cause acute and chronic health effects when inhaled. The International Agency for Research on Cancer (IARC) classified Welding Fumes as carcinogenic to humans (Group 1) in 2017, based on sufficient epidemiological evidence and limited evidence in animals, an upgrade from the former Group 2B (possibly carcinogenic to humans) classification. There is human evidence that both iron-abundant mild steel as well as chromium- and nickel-containing stainless steel Welding Fumes contribute to an increased risk of lung cancer. Recent animal studies show that Welding Fumes may act as lung tumor promoters, regardless of the presence or absence of potentially carcinogenic metals, such as chromium and nickel. The goal of this manuscript was to examine the pulmonary responses associated with Welding Fumes by reviewing a series of recent experimental animal studies that assessed the influence of Welding Fume metal composition (e.g., stainless steel versus mild steel Welding Fume) on markers of lung toxicity and tumor development. Additional in vivo laboratory studies are needed to further explore the association between Welding and lung cancer and to help advance our understanding of a potential mechanistic link.
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altered ion transport in normal human bronchial epithelial cells following exposure to chemically distinct metal Welding Fume particles
Toxicology and Applied Pharmacology, 2017Co-Authors: Jeffrey S Fedan, Terence Meighan, Patti C Zeidlererdely, Janet A Thompson, James M AntoniniAbstract:Abstract Welding Fume inhalation causes pulmonary toxicity, including susceptibility to infection. We hypothesized that airway epithelial ion transport is a target of Fume toxicity, and investigated the effects of Fume particulates from manual metal arc-stainless steel (MMA-SS) and gas metal arc-mild steel (GMA-MS) on ion transport in normal human bronchial epithelium (NHBE) cultured in air-interface. MMA-SS particles, more soluble than GMA-MS particles, contain Cr, Ni, Fe and Mn; GMA-MS particles contain Fe and Mn. MMA-SS or GMA-MS particles (0.0167–166.7 μg/cm 2 ) were applied apically to NHBEs. After 18 h transepithelial potential difference (V t ), resistance (R t ), and short circuit current ( I sc ) were measured. Particle effects on Na + and Cl¯ channels and the Na + ,K + ,2Cl¯-cotransporter were evaluated using amiloride (apical), 5-nitro-2-[(3-phenylpropyl)amino]benzoic acid (NPPB, apical), and bumetanide (basolateral), respectively. MMA-SS (0.0167–16.7 μg/cm 2 ) increased basal V t . Only 16.7 μg/cm 2 GMA-MS increased basal V t significantly. MMA-SS or GMA-MS exposure potentiated I sc responses (decreases) to amiloride and bumetanide, while not affecting those to NPPB, GMA-MS to a lesser degree than MMA-SS. Variable effects on R t were observed in response to amiloride, and bumetanide. Generally, MMA-SS was more potent in altering responses to amiloride and bumetanide than GMA-MS. Hyperpolarization occurred in the absence of LDH release, but decreases in V t , R t , and I sc at higher Fume particulate doses accompanied LDH release, to a greater extent for MMA-SS. Thus, Na + transport and Na + ,K + ,2Cl¯-cotransport are affected by Fume exposure; MMA-MS is more potent than GMA-MS. Enhanced Na + absorption and decreased airway surface liquid could compromise defenses against infection.
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comparative microscopic study of human and rat lungs after overexposure to Welding Fume
Annals of Occupational Hygiene, 2013Co-Authors: James M Antonini, Diane Schweglerberry, Jenny R Roberts, Robert R MercerAbstract:Welding is a common industrial process used to join metals and generates complex aerosols of potentially hazardous metal Fumes and gases. Most long-time welders experience some type of respiratory disorder during their time of employment. The use of animal models and the ability to control the Welding Fume exposure in toxicology studies have been helpful in developing a better understanding of how Welding Fumes affect health. There are no studies that have performed a side-by-side comparison of the pulmonary responses from an animal toxicology Welding Fume study with the lung responses associated with chronic exposure to Welding Fume by a career welder. In this study, post-mortem lung tissue was donated from a long-time welder with a well-characterized work background and a history of extensive Welding Fume exposure. To simulate a long-term Welding exposure in an animal model, Sprague-Dawley rats were treated once a week for 28 weeks by intratracheal instillation with 2mg of a stainless steel, hard-surfacing Welding Fume. Lung tissues from the welder and the Welding Fume-treated rats were examined by light and electron microscopy. Pathological analysis of lung tissue collected from the welder demonstrated inflammatory cell influx and significant pulmonary injury. The poor and deteriorating lung condition observed in the welder examined in this study was likely due to exposure to very high levels of potentially toxic metal Fumes and gases for a significant number of years due to work in confined spaces. The lung toxicity profile for the rats treated with Welding Fume was similar. For tissue samples from both the welder and treated rats, Welding particle accumulations deposited and persisted in lung structures and were easily visualized using light microscopic techniques. Agglomerates of deposited Welding particles mostly were observed within lung cells, particularly alveolar macrophages. Analysis of individual particles within the agglomerates showed that these particles were metal complexes with iron, chromium, and nickel being the most common metals present. In conclusion, long-term exposure to specific Welding Fume can lead to serious chronic lung disease characterized by significant particle deposition and persistence as demonstrated in both a human case study and rat model. Not only were the lung responses similar in the human and rat lungs, as evidenced by inflammatory cell influx and pulmonary disease, but the composition of individual Welding particles and agglomerations in situ was comparable.
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Open Access Comparison of stainless and mild steel Welding Fumes in generation of reactive oxygen species
2013Co-Authors: Stephen S Leonard, Bean T Chen, Samuel G Stone, Diane Schwegler-berry, Allison J Kenyon, David Frazer, James M AntoniniAbstract:Background: Welding Fumes consist of a wide range of complex metal oxide particles which can be deposited in all regions of the respiratory tract. The Welding aerosol is not homogeneous and is generated mostly from the electrode/wire. Over 390,000 welders were reported in the U.S. in 2008 while over 1 million full-time welders were working worldwide. Many health effects are presently under investigation from exposure to Welding Fumes. Welding Fume pulmonary effects have been associated with bronchitis, metal Fume fever, cancer and functional changes in the lung. Our investigation focused on the generation of free radicals and reactive oxygen species from stainless and mild steel Welding Fumes generated by a gas metal arc robotic welder. An inhalation exposure chamber located at NIOSH was used to collect the Welding Fume particles. Results: Our results show that hydroxyl radicals (. OH) were generated from reactions with H2O2 and after exposure to cells. Catalase reduced the generation of. OH from exposed cells indicating the involvement of H2O2. The Welding Fume suspension also showed the ability to cause lipid peroxidation, effect O2 consumption, induce H2O2 generation in cells, and cause DNA damage. Conclusion: Increase in oxidative damage observed in the cellular exposures correlated well with. OH generation in size and type of Welding Fumes, indicating the influence of metal type and transition state on radical productio
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immunotoxicology of arc Welding Fume worker and experimental animal studies
Journal of Immunotoxicology, 2012Co-Authors: Patti C Zeidlererdely, Aaron Erdely, James M AntoniniAbstract:Arc Welding processes generate complex aerosols composed of potentially hazardous metal Fumes and gases. Millions of workers worldwide are exposed to Welding aerosols daily. A health effect of Welding that is of concern to the occupational health community is the development of immune system dysfunction. Increased severity, frequency, and duration of upper and lower respiratory tract infections have been reported among welders. Specifically, multiple studies have observed an excess mortality from pneumonia in welders and workers exposed to metal Fumes. Although several welder cohort and experimental animal studies investigating the adverse effects of Welding Fume exposure on immune function have been performed, the potential mechanisms responsible for these effects are limited. The objective of this report was to review both human and animal studies that have examined the effect of Welding Fume pulmonary exposure on local and systemic immune responses.
Jenny R Roberts - One of the best experts on this subject based on the ideXlab platform.
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comparative microscopic study of human and rat lungs after overexposure to Welding Fume
Annals of Occupational Hygiene, 2013Co-Authors: James M Antonini, Diane Schweglerberry, Jenny R Roberts, Robert R MercerAbstract:Welding is a common industrial process used to join metals and generates complex aerosols of potentially hazardous metal Fumes and gases. Most long-time welders experience some type of respiratory disorder during their time of employment. The use of animal models and the ability to control the Welding Fume exposure in toxicology studies have been helpful in developing a better understanding of how Welding Fumes affect health. There are no studies that have performed a side-by-side comparison of the pulmonary responses from an animal toxicology Welding Fume study with the lung responses associated with chronic exposure to Welding Fume by a career welder. In this study, post-mortem lung tissue was donated from a long-time welder with a well-characterized work background and a history of extensive Welding Fume exposure. To simulate a long-term Welding exposure in an animal model, Sprague-Dawley rats were treated once a week for 28 weeks by intratracheal instillation with 2mg of a stainless steel, hard-surfacing Welding Fume. Lung tissues from the welder and the Welding Fume-treated rats were examined by light and electron microscopy. Pathological analysis of lung tissue collected from the welder demonstrated inflammatory cell influx and significant pulmonary injury. The poor and deteriorating lung condition observed in the welder examined in this study was likely due to exposure to very high levels of potentially toxic metal Fumes and gases for a significant number of years due to work in confined spaces. The lung toxicity profile for the rats treated with Welding Fume was similar. For tissue samples from both the welder and treated rats, Welding particle accumulations deposited and persisted in lung structures and were easily visualized using light microscopic techniques. Agglomerates of deposited Welding particles mostly were observed within lung cells, particularly alveolar macrophages. Analysis of individual particles within the agglomerates showed that these particles were metal complexes with iron, chromium, and nickel being the most common metals present. In conclusion, long-term exposure to specific Welding Fume can lead to serious chronic lung disease characterized by significant particle deposition and persistence as demonstrated in both a human case study and rat model. Not only were the lung responses similar in the human and rat lungs, as evidenced by inflammatory cell influx and pulmonary disease, but the composition of individual Welding particles and agglomerations in situ was comparable.
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Persistence of deposited metals in the lungs after stainless steel and mild steel Welding Fume inhalation in rats
Archives of Toxicology, 2011Co-Authors: James M Antonini, Samuel Stone, Jenny R Roberts, Bean T Chen, Diane Schwegler-berry, Ronnee N Andrews, Rebecca Chapman, Patti C. Zeidler-erdely, David G FrazerAbstract:Welding generates complex metal Fumes that vary in composition. The objectives of this study were to compare the persistence of deposited metals and the inflammatory potential of stainless and mild steel Welding Fumes, the two most common Fumes used in US industry. Sprague–Dawley rats were exposed to 40 mg/m^3 of stainless or mild steel Welding Fumes for 3 h/day for 3 days. Controls were exposed to filtered air. Generated Fume was collected, and particle size and elemental composition were determined. Bronchoalveolar lavage was done on days 0, 8, 21, and 42 after the last exposure to assess lung injury/inflammation and to recover lung phagocytes. Non-lavaged lung samples were analyzed for total and specific metal content as a measure of metal persistence. Both Welding Fumes were similar in particle morphology and size. Following was the chemical composition of the Fumes—stainless steel: 57% Fe, 20% Cr, 14% Mn, and 9% Ni; mild steel: 83% Fe and 15% Mn. There was no effect of the mild steel Fume on lung injury/inflammation at any time point compared to air control. Lung injury and inflammation were significantly elevated at 8 and 21 days after exposure to the stainless steel Fume compared to control. Stainless steel Fume exposure was associated with greater recovery of Welding Fume-laden macrophages from the lungs at all time points compared with the mild steel Fume. A higher concentration of total metal was observed in the lungs of the stainless steel Welding Fume at all time points compared with the mild steel Fume. The specific metals present in the two Fumes were cleared from the lungs at different rates. The potentially more toxic metals (e.g., Mn, Cr) present in the stainless steel Fume were cleared from the lungs more quickly than Fe, likely increasing their translocation from the respiratory system to other organs.
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mild steel Welding Fume causes manganese accumulation and subtle neuroinflammatory changes but not overt neuronal damage in discrete brain regions of rats after short term inhalation exposure
Neurotoxicology, 2009Co-Authors: James M Antonini, Samuel Stone, Diane Schweglerberry, Jenny R Roberts, Bean T Chen, Krishnan Sriram, Stanley A Benkovic, Amy M Jefferson, Brenda K Billig, Christopher M FeltonAbstract:Abstract Serious questions have been raised by occupational health investigators regarding a possible causal association between neurological effects in welders and the presence of manganese (Mn) in Welding Fume. Male Sprague–Dawley rats were exposed by inhalation to 40 mg/m 3 of gas metal arc-mild steel (MS) Welding Fume for 3 h/day for 10 days. Generated Fume was collected in the animal chamber during exposure, and particle size, composition, and morphology were characterized. At 1 day after the last exposure, metal deposition in different organ systems and neurological responses in dopaminergic brain regions were assessed in exposed animals. The Welding particles were composed primarily of a complex of iron (Fe) and Mn and were arranged as chain-like aggregates with a significant number of particles in the nanometer size range. Mn was observed to translocate from the lungs to the kidney and specific brain regions (olfactory bulb, cortex, and cerebellum) after MS Fume inhalation. In terms of neurological responses, short-term MS Fume inhalation induced significant elevations in divalent metal ion transporter 1 (Dmt1) expression in striatum and midbrain and significant increases in expression of proinflammatory chemokines (Ccl2, Cxcl2) and cytokines (IL1β, TNFα) in striatum. In addition, mRNA and protein expression of glial fibrillary acidic protein (GFAP) was significantly increased in striatum after MS Fume exposure. However, the 10-day MS Welding Fume inhalation did not cause any changes in dopamine and its metabolites or GABA in dopaminergic brain regions nor did it produce overt neural cell damage as assessed by histopathology. In summary, short-term MS Welding Fume exposure led to translocation of Mn to specific brain regions and induced subtle changes in cell markers of neuroinflammatory and astrogliosis. The neurofunctional significance of these findings currently is being investigated in longer, more chronic Welding Fume exposure studies.
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pulmonary inflammation and tumor induction in lung tumor susceptible a j and resistant c57bl 6j mice exposed to Welding Fume
Particle and Fibre Toxicology, 2008Co-Authors: Patti C Zeidlererdely, Jenny R Roberts, Shihhoung Young, Aaron Erdely, Lori A Battelli, Michael L Kashon, Steven H Reynolds, James M AntoniniAbstract:Welding Fume has been categorized as "possibly carcinogenic" to humans. Our objectives were to characterize the lung response to carcinogenic and non-carcinogenic metal-containing Welding Fumes and to determine if these Fumes caused increased lung tumorigenicity in A/J mice, a lung tumor susceptible strain. We exposed male A/J and C57BL/6J, a lung tumor resistant strain, by pharyngeal aspiration four times (once every 3 days) to 85 μg of gas metal arc-mild steel (GMA-MS), GMA-stainless steel (SS), or manual metal arc-SS (MMA-SS) Fume, or to 25.5 μg soluble hexavalent chromium (S-Cr). Shams were exposed to saline vehicle. Bronchoalveolar lavage (BAL) was done at 2, 7, and 28 days post-exposure. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 48 and 78 weeks post-exposure. BAL revealed notable strain-dependent differences with regards to the degree and resolution of the inflammatory response after exposure to the Fumes. At 48 weeks, carcinogenic metal-containing GMA-SS Fume caused the greatest increase in tumor multiplicity and incidence, but this was not different from sham. By 78 weeks, tumor incidence in the GMA-SS group versus sham approached significance (p = 0.057). A significant increase in perivascular/peribronchial lymphoid infiltrates for the GMA-SS group versus sham and an increased persistence of this Fume in lung cells compared to the other Welding Fumes was found. The increased persistence of GMA-SS Fume in combination with its metal composition may trigger a chronic, but mild, inflammatory state in the lung possibly enhancing tumorigenesis in this susceptible mouse strain.
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effect of short term stainless steel Welding Fume inhalation exposure on lung inflammation injury and defense responses in rats
Toxicology and Applied Pharmacology, 2007Co-Authors: James M Antonini, Samuel Stone, Diane Schweglerberry, Bean Chen, Aliakbar Afshari, Jenny R Roberts, David G FrazerAbstract:Many welders have experienced bronchitis, metal Fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of Welding Fume exposure. The objective was to assess the early effects of stainless steel (SS) Welding Fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS Welding Fume at a concentration of 15 or 40 mg/m{sup 3} x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses, some animals were intratracheally inoculated with 5 x 10{sup 4}Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generatedmore » Fume to be 0.255 {mu}m. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS Welding Fume caused significant lung damage and suppressed lung defense responses to bacterial infection, but had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS Welding Fume exposure.« less
Bean T Chen - One of the best experts on this subject based on the ideXlab platform.
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size distribution and estimated respiratory deposition of total chromium hexavalent chromium manganese and nickel in gas metal arc Welding Fume aerosols
Aerosol Science and Technology, 2014Co-Authors: Lorenzo Cena, Michael J Keane, William P Chisholm, Amy Cumpston, Bean T ChenAbstract:A laboratory study was conducted to determine the mass of total Cr, Cr(VI), Mn, and Ni in 15 size fractions for mild and stainless steel gas-metal arc Welding (GMAW) Fumes. Samples were collected using a nano multi orifice uniform deposition impactor (MOUDI) with polyvinyl chloride filters on each stage. The filters were analyzed by inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography. Limits of detection (LODs) and quantitation (LOQs) were experimentally calculated and percent recoveries were measured from spiked metals in solution and dry, certified Welding-Fume reference material. The fraction of Cr(VI) in total Cr was estimated by calculating the ratio of Cr(VI) to total Cr mass for each particle size range. Expected, regional deposition of each metal was estimated according to respiratory-deposition models. The weight percent (standard deviation) of Mn in mild steel Fumes was 9.2% (6.8%). For stainless steel Fumes, the weight percentages were 8.4% (5.4%) for total Cr, 12.2% (6.5%) for Mn, 2.1% (1.5%) for Ni and 0.5% (0.4%) for Cr(VI). All metals presented a fraction between 0.04 and 0.6 μm. Total Cr and Ni presented an additional fraction <0.03 μm. On average 6% of the Cr was found in the Cr(VI) valence state. There was no statistical difference between the smallest and largest mean Cr(VI) to total Cr mass ratio (p-value D 0.19), hence our analysis does not show that particle size affects the contribution of Cr(VI) to total Cr. The predicted total respiratory deposition for the metal particles was ∼25%. The sites of principal deposition were the head airways (7-10%) and the alveolar region (11-14%). Estimated Cr(VI) deposition was highest in the alveolar region (14%).
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a novel method for assessing respiratory deposition of Welding Fume nanoparticles
Journal of Occupational and Environmental Hygiene, 2014Co-Authors: Lorenzo Cena, Samuel Stone, Michael J Keane, William P Chisholm, Martin Harper, Bean T ChenAbstract:Welders are exposed to high concentrations of nanoparticles. Compared to larger particles, nanoparticles have been associated with more toxic effects at the cellular level, including the generation of more reactive oxygen species activity. Current methods for Welding-Fume aerosol exposures do not differentiate between the nano-fraction and the larger particles. The objectives of this work are to establish a method to estimate the respiratory deposition of the nano-fraction of selected metals in Welding Fumes and test this method in a laboratory setting. Manganese (Mn), Nickel (Ni), Chromium (Cr), and hexavalent chromium (Cr(VI)) are commonly found in Welding Fume aerosols and have been linked with severe adverse health outcomes. Inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography (IC) were evaluated as methods for analyzing the content of Mn, Ni, Cr, and Cr(VI) nanoparticles in Welding Fumes collected with nanoparticle respiratory deposition (NRD) samplers. NRD samplers collect na...
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Open Access Comparison of stainless and mild steel Welding Fumes in generation of reactive oxygen species
2013Co-Authors: Stephen S Leonard, Bean T Chen, Samuel G Stone, Diane Schwegler-berry, Allison J Kenyon, David Frazer, James M AntoniniAbstract:Background: Welding Fumes consist of a wide range of complex metal oxide particles which can be deposited in all regions of the respiratory tract. The Welding aerosol is not homogeneous and is generated mostly from the electrode/wire. Over 390,000 welders were reported in the U.S. in 2008 while over 1 million full-time welders were working worldwide. Many health effects are presently under investigation from exposure to Welding Fumes. Welding Fume pulmonary effects have been associated with bronchitis, metal Fume fever, cancer and functional changes in the lung. Our investigation focused on the generation of free radicals and reactive oxygen species from stainless and mild steel Welding Fumes generated by a gas metal arc robotic welder. An inhalation exposure chamber located at NIOSH was used to collect the Welding Fume particles. Results: Our results show that hydroxyl radicals (. OH) were generated from reactions with H2O2 and after exposure to cells. Catalase reduced the generation of. OH from exposed cells indicating the involvement of H2O2. The Welding Fume suspension also showed the ability to cause lipid peroxidation, effect O2 consumption, induce H2O2 generation in cells, and cause DNA damage. Conclusion: Increase in oxidative damage observed in the cellular exposures correlated well with. OH generation in size and type of Welding Fumes, indicating the influence of metal type and transition state on radical productio
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inhalation exposure of gas metal arc stainless steel Welding Fume increased atherosclerotic lesions in apolipoprotein e knockout mice
Toxicology Letters, 2011Co-Authors: Aaron Erdely, James M Antonini, Samuel Stone, Bean T Chen, Patti C Zeidlererdely, Rebecca Salmenmuniz, David G Frazer, Tracy Hulderman, Angie Liston, Petia P SimeonovaAbstract:Epidemiological studies suggest that Welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) Welding Fume exposure. Apolipoprotein E knockout (apoE(-/-)) mice, fed a Western diet, were exposed to GMA-SS at 40mg/m(3) for 3h/day for ten days (∼8.26μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE(-/-) mice. These results complement epidemiological and functional human studies that suggest Welding may result in adverse cardiovascular effects.
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Persistence of deposited metals in the lungs after stainless steel and mild steel Welding Fume inhalation in rats
Archives of Toxicology, 2011Co-Authors: James M Antonini, Samuel Stone, Jenny R Roberts, Bean T Chen, Diane Schwegler-berry, Ronnee N Andrews, Rebecca Chapman, Patti C. Zeidler-erdely, David G FrazerAbstract:Welding generates complex metal Fumes that vary in composition. The objectives of this study were to compare the persistence of deposited metals and the inflammatory potential of stainless and mild steel Welding Fumes, the two most common Fumes used in US industry. Sprague–Dawley rats were exposed to 40 mg/m^3 of stainless or mild steel Welding Fumes for 3 h/day for 3 days. Controls were exposed to filtered air. Generated Fume was collected, and particle size and elemental composition were determined. Bronchoalveolar lavage was done on days 0, 8, 21, and 42 after the last exposure to assess lung injury/inflammation and to recover lung phagocytes. Non-lavaged lung samples were analyzed for total and specific metal content as a measure of metal persistence. Both Welding Fumes were similar in particle morphology and size. Following was the chemical composition of the Fumes—stainless steel: 57% Fe, 20% Cr, 14% Mn, and 9% Ni; mild steel: 83% Fe and 15% Mn. There was no effect of the mild steel Fume on lung injury/inflammation at any time point compared to air control. Lung injury and inflammation were significantly elevated at 8 and 21 days after exposure to the stainless steel Fume compared to control. Stainless steel Fume exposure was associated with greater recovery of Welding Fume-laden macrophages from the lungs at all time points compared with the mild steel Fume. A higher concentration of total metal was observed in the lungs of the stainless steel Welding Fume at all time points compared with the mild steel Fume. The specific metals present in the two Fumes were cleared from the lungs at different rates. The potentially more toxic metals (e.g., Mn, Cr) present in the stainless steel Fume were cleared from the lungs more quickly than Fe, likely increasing their translocation from the respiratory system to other organs.
Samuel Stone - One of the best experts on this subject based on the ideXlab platform.
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inhalation of gas metal arc stainless steel Welding Fume promotes lung tumorigenesis in a j mice
Archives of Toxicology, 2017Co-Authors: Samuel Stone, Walter Mckinney, Aaron Erdely, Lori A Battelli, Lauryn M Falcone, Terence Meighan, Rebecca Salmen, Amy Cumpston, Jared L CumpstonAbstract:Epidemiologic studies suggest an increased risk of lung cancer with exposure to Welding Fumes, but controlled animal studies are needed to support this association. Oropharyngeal aspiration of collected “aged” gas metal arc–stainless steel (GMA–SS) Welding Fume has been shown by our laboratory to promote lung tumor formation in vivo using a two-stage initiation–promotion model. Our objective in this study was to determine whether inhalation of freshly generated GMA-SS Welding Fume also acts as a lung tumor promoter in lung tumor-susceptible mice. Male A/J mice received intraperitoneal (IP) injections of corn oil or the chemical initiator 3-methylcholanthrene (MCA; 10 µg/g) and 1 week later were exposed by whole-body inhalation to air or GMA-SS Welding aerosols for 4 h/d × 4 d/w × 9 w at a target concentration of 40 mg/m3. Lung nodules were enumerated at 30 weeks post-initiation. GMA-SS Fume significantly promoted lung tumor multiplicity in A/J mice initiated with MCA (16.11 ± 1.18) compared to MCA/air-exposed mice (7.93 ± 0.82). Histopathological analysis found that the increased number of lung nodules in the MCA/GMA-SS group were hyperplasias and adenomas, which was consistent with developing lung tumorigenesis. Metal deposition analysis in the lung revealed a lower deposited dose, approximately fivefold compared to our previous aspiration study, still elicited a significant lung tumorigenic response. In conclusion, this study demonstrates that inhaling GMA-SS Welding Fume promotes lung tumorigenesis in vivo which is consistent with the epidemiologic studies that show welders may be at an increased risk for lung cancer.
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a novel method for assessing respiratory deposition of Welding Fume nanoparticles
Journal of Occupational and Environmental Hygiene, 2014Co-Authors: Lorenzo Cena, Samuel Stone, Michael J Keane, William P Chisholm, Martin Harper, Bean T ChenAbstract:Welders are exposed to high concentrations of nanoparticles. Compared to larger particles, nanoparticles have been associated with more toxic effects at the cellular level, including the generation of more reactive oxygen species activity. Current methods for Welding-Fume aerosol exposures do not differentiate between the nano-fraction and the larger particles. The objectives of this work are to establish a method to estimate the respiratory deposition of the nano-fraction of selected metals in Welding Fumes and test this method in a laboratory setting. Manganese (Mn), Nickel (Ni), Chromium (Cr), and hexavalent chromium (Cr(VI)) are commonly found in Welding Fume aerosols and have been linked with severe adverse health outcomes. Inductively coupled plasma mass spectrometry (ICP-MS) and ion chromatography (IC) were evaluated as methods for analyzing the content of Mn, Ni, Cr, and Cr(VI) nanoparticles in Welding Fumes collected with nanoparticle respiratory deposition (NRD) samplers. NRD samplers collect na...
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inhalation exposure of gas metal arc stainless steel Welding Fume increased atherosclerotic lesions in apolipoprotein e knockout mice
Toxicology Letters, 2011Co-Authors: Aaron Erdely, James M Antonini, Samuel Stone, Bean T Chen, Patti C Zeidlererdely, Rebecca Salmenmuniz, David G Frazer, Tracy Hulderman, Angie Liston, Petia P SimeonovaAbstract:Epidemiological studies suggest that Welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) Welding Fume exposure. Apolipoprotein E knockout (apoE(-/-)) mice, fed a Western diet, were exposed to GMA-SS at 40mg/m(3) for 3h/day for ten days (∼8.26μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE(-/-) mice. These results complement epidemiological and functional human studies that suggest Welding may result in adverse cardiovascular effects.
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Persistence of deposited metals in the lungs after stainless steel and mild steel Welding Fume inhalation in rats
Archives of Toxicology, 2011Co-Authors: James M Antonini, Samuel Stone, Jenny R Roberts, Bean T Chen, Diane Schwegler-berry, Ronnee N Andrews, Rebecca Chapman, Patti C. Zeidler-erdely, David G FrazerAbstract:Welding generates complex metal Fumes that vary in composition. The objectives of this study were to compare the persistence of deposited metals and the inflammatory potential of stainless and mild steel Welding Fumes, the two most common Fumes used in US industry. Sprague–Dawley rats were exposed to 40 mg/m^3 of stainless or mild steel Welding Fumes for 3 h/day for 3 days. Controls were exposed to filtered air. Generated Fume was collected, and particle size and elemental composition were determined. Bronchoalveolar lavage was done on days 0, 8, 21, and 42 after the last exposure to assess lung injury/inflammation and to recover lung phagocytes. Non-lavaged lung samples were analyzed for total and specific metal content as a measure of metal persistence. Both Welding Fumes were similar in particle morphology and size. Following was the chemical composition of the Fumes—stainless steel: 57% Fe, 20% Cr, 14% Mn, and 9% Ni; mild steel: 83% Fe and 15% Mn. There was no effect of the mild steel Fume on lung injury/inflammation at any time point compared to air control. Lung injury and inflammation were significantly elevated at 8 and 21 days after exposure to the stainless steel Fume compared to control. Stainless steel Fume exposure was associated with greater recovery of Welding Fume-laden macrophages from the lungs at all time points compared with the mild steel Fume. A higher concentration of total metal was observed in the lungs of the stainless steel Welding Fume at all time points compared with the mild steel Fume. The specific metals present in the two Fumes were cleared from the lungs at different rates. The potentially more toxic metals (e.g., Mn, Cr) present in the stainless steel Fume were cleared from the lungs more quickly than Fe, likely increasing their translocation from the respiratory system to other organs.
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short term inhalation of stainless steel Welding Fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible a j mice
Inhalation Toxicology, 2011Co-Authors: Patti C Zeidlererdely, Samuel Stone, Bean T Chen, Shihhoung Young, Aaron Erdely, Lori A Battelli, Michael L Kashon, David G Frazer, Ronnee N Andrews, James M AntoniniAbstract:Debate exists as to whether Welding Fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) Welding Fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS Welding Fume at 40 mg/m3 × 3 h/day for 6 and 10 days. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS Fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed ...
David G Frazer - One of the best experts on this subject based on the ideXlab platform.
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inhalation exposure of gas metal arc stainless steel Welding Fume increased atherosclerotic lesions in apolipoprotein e knockout mice
Toxicology Letters, 2011Co-Authors: Aaron Erdely, James M Antonini, Samuel Stone, Bean T Chen, Patti C Zeidlererdely, Rebecca Salmenmuniz, David G Frazer, Tracy Hulderman, Angie Liston, Petia P SimeonovaAbstract:Epidemiological studies suggest that Welding, a process which generates an aerosol of inhalable gases and metal rich particulates, increases the risk for cardiovascular disease. In this study we analyzed systemic inflammation and atherosclerotic lesions following gas metal arc-stainless steel (GMA-SS) Welding Fume exposure. Apolipoprotein E knockout (apoE(-/-)) mice, fed a Western diet, were exposed to GMA-SS at 40mg/m(3) for 3h/day for ten days (∼8.26μg daily alveolar deposition). Mice were sacrificed two weeks after exposure and serum chemistry, serum protein profiling and aortic lesion area were determined. There were no significant changes in serum total cholesterol, triglycerides or alanine aminotransferase. Serum levels of uric acid, a potent antioxidant, were decreased perhaps suggesting a reduced capacity to combat systemic oxidative stress. Inflammatory serum proteins interleukin 1 beta (IL-1β) and monocyte chemoattractant protein 3 (MCP-3) were increased two weeks after GMA-SS exposure. Analysis of atherosclerotic plaques showed an increase in lesion area as the result of GMA-SS exposure. In conclusion, GMA-SS exposure showed evidence of systemic inflammation and increased plaque progression in apoE(-/-) mice. These results complement epidemiological and functional human studies that suggest Welding may result in adverse cardiovascular effects.
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Persistence of deposited metals in the lungs after stainless steel and mild steel Welding Fume inhalation in rats
Archives of Toxicology, 2011Co-Authors: James M Antonini, Samuel Stone, Jenny R Roberts, Bean T Chen, Diane Schwegler-berry, Ronnee N Andrews, Rebecca Chapman, Patti C. Zeidler-erdely, David G FrazerAbstract:Welding generates complex metal Fumes that vary in composition. The objectives of this study were to compare the persistence of deposited metals and the inflammatory potential of stainless and mild steel Welding Fumes, the two most common Fumes used in US industry. Sprague–Dawley rats were exposed to 40 mg/m^3 of stainless or mild steel Welding Fumes for 3 h/day for 3 days. Controls were exposed to filtered air. Generated Fume was collected, and particle size and elemental composition were determined. Bronchoalveolar lavage was done on days 0, 8, 21, and 42 after the last exposure to assess lung injury/inflammation and to recover lung phagocytes. Non-lavaged lung samples were analyzed for total and specific metal content as a measure of metal persistence. Both Welding Fumes were similar in particle morphology and size. Following was the chemical composition of the Fumes—stainless steel: 57% Fe, 20% Cr, 14% Mn, and 9% Ni; mild steel: 83% Fe and 15% Mn. There was no effect of the mild steel Fume on lung injury/inflammation at any time point compared to air control. Lung injury and inflammation were significantly elevated at 8 and 21 days after exposure to the stainless steel Fume compared to control. Stainless steel Fume exposure was associated with greater recovery of Welding Fume-laden macrophages from the lungs at all time points compared with the mild steel Fume. A higher concentration of total metal was observed in the lungs of the stainless steel Welding Fume at all time points compared with the mild steel Fume. The specific metals present in the two Fumes were cleared from the lungs at different rates. The potentially more toxic metals (e.g., Mn, Cr) present in the stainless steel Fume were cleared from the lungs more quickly than Fe, likely increasing their translocation from the respiratory system to other organs.
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short term inhalation of stainless steel Welding Fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible a j mice
Inhalation Toxicology, 2011Co-Authors: Patti C Zeidlererdely, Samuel Stone, Bean T Chen, Shihhoung Young, Aaron Erdely, Lori A Battelli, Michael L Kashon, David G Frazer, Ronnee N Andrews, James M AntoniniAbstract:Debate exists as to whether Welding Fume is carcinogenic, but epidemiological evidence suggests that welders are an at-risk population for development of lung cancer. Our objective was to expose, by inhalation, lung tumor susceptible (A/J) and resistant C57BL/6J (B6) mice to stainless steel (SS) Welding Fume containing carcinogenic metals and characterize the lung-inflammatory and tumorigenic response. Male mice were exposed to air or gas metal arc (GMA)-SS Welding Fume at 40 mg/m3 × 3 h/day for 6 and 10 days. At 1, 4, 7, 10, 14, and 28 days after 10 days of exposure, bronchoalveolar lavage (BAL) was done. Lung cytotoxicity, permeability, inflammatory cytokines, and cell differentials were analyzed. For the lung tumor study, gross tumor counts and histopathological changes were assessed in A/J mice at 78 weeks after 6 and 10 days of exposure. Inhalation of GMA-SS Fume caused an early, sustained macrophage and lymphocyte response followed by a gradual neutrophil influx and the magnitudes of these differed ...
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effect of short term stainless steel Welding Fume inhalation exposure on lung inflammation injury and defense responses in rats
Toxicology and Applied Pharmacology, 2007Co-Authors: James M Antonini, Samuel Stone, Diane Schweglerberry, Bean Chen, Aliakbar Afshari, Jenny R Roberts, David G FrazerAbstract:Many welders have experienced bronchitis, metal Fume fever, lung function changes, and an increase in the incidence of lung infection. Questions remain regarding the possible mechanisms associated with the potential pulmonary effects of Welding Fume exposure. The objective was to assess the early effects of stainless steel (SS) Welding Fume inhalation on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to gas metal arc-SS Welding Fume at a concentration of 15 or 40 mg/m{sup 3} x 3 h/day for 1, 3, or 10 days. The control group was exposed to filtered air. To assess lung defense responses, some animals were intratracheally inoculated with 5 x 10{sup 4}Listeria monocytogenes 1 day after the last exposure. Welding particles were collected during exposure, and elemental composition and particle size were determined. At 1, 4, 6, 11, 14, and 30 days after the final exposure, parameters of lung injury (lactate dehydrogenase and albumin) and inflammation (PMN influx) were measured in the bronchoalveolar lavage fluid. In addition, particle-induced effects on pulmonary clearance of bacteria and macrophage function were assessed. SS particles were composed of Fe, Cr, Mn, and Ni. Particle size distribution analysis indicated the mass median aerodynamic diameter of the generatedmore » Fume to be 0.255 {mu}m. Parameters of lung injury were significantly elevated at all time points post-exposure compared to controls except for 30 days. Interestingly, no significant difference in lung PMNs was observed between the SS and control groups at 1, 4, and 6 days post-exposure. After 6 days post-exposure, a dramatic increase in lung PMNs was observed in the SS group compared to air controls. Lung bacteria clearance and macrophage function were reduced and immune and inflammatory cytokines were altered in the SS group. In summary, short-term exposure of rats to SS Welding Fume caused significant lung damage and suppressed lung defense responses to bacterial infection, but had a delayed effect on pulmonary inflammation. Additional chronic inhalation studies are needed to further examine the lung effects associated with SS Welding Fume exposure.« less
