Lung fibrosis in Sprague-Dawley rats, induced by exposure to manual metal arc-stainless steel welding fumes.

To investigate the disease process of pneumoconiosis induced by welding-fume exposure, a lung fibrosis model was established by building a stainless steel arc welding fume generation system and exposing male Sprague-Dawley rats for 90 days. The rats were exposed to welding fumes with concentrations of 57-67 mg/m3 (low dose) and 105-118 mg/m3 (high dose) total suspended particulates for 2 h per day in an inhalation chamber for 90 days. The concentrations of the main metals, Fe, Mn, Cr, and Ni, were measured in the welding fumes, plus the gaseous compounds, including nitrous gases and ozone, were monitored. During the exposure period, the animals were sacrificed after the initial 2-h exposure and after 15, 30, 60, and 90 days. Histopathological examinations were conducted on the animals' upper respiratory tract, including the nasal pathway and conducting airway, plus the gas exchange region, including the alveolar ducts, alveolar sacs, and alveoli. When compared to the control group, the lung weights did not increase significantly in the low-dose group, yet in the high-dose group there was a significant increase from day 15 to day 90. The histopathological examination combined with fibrosis-specific staining (Masson's trichrome) indicated that the lungs in the low-dose group did not exhibit any progressive fibrotic changes. Whereas, the lungs in the high-dose group exhibited early delicate fibrosis from day 15, which progressed into the perivascular and peribronchiolar regions by day 30. Interstitial fibrosis appeared at day 60 and became prominent by day 90, along with the additional appearance of pleural fibrosis. Accordingly, it would appear that a significant dose of welding-fume exposure was required to induce lung fibrosis.     

Short-term inhalation exposure to mild steel welding fume had no effect on lung inflammation and injury but did alter defense responses to bacteria in rats

Many workers worldwide are continually exposed to complex aerosols generated from welding processes. The objective was to assess the effect of inhalation exposure to mild steel (MS) welding fume on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to MS fume at a concentration of 40 mg/m(3) x 3 h/day x 3 or 10 days using a robotic welding fume generator. Controls were exposed to filtered air. To assess lung defense responses, a group of animals were intratracheally inoculated with 5 x 10(4) Listeria monocytogenes 1 day after the last daily exposure. Welding particles were collected during exposure, and chemical composition and particle size were determined. After exposure, lung injury, inflammation, and host defense (bacterial clearance) were measured. The particles were composed of iron (80.6 %) and manganese (14.7 %) with a mass median aerodynamic diameter of 0.31 microm. No significant difference was observed in lung injury or inflammation after MS fume inhalation at 1, 4, and 11 days after the last exposure. However, there were significantly more bacteria at 3 days after infection in the lungs of the animals exposed to MS fume compared to air controls. Acute exposure of rats to MS fume had no effect on injury and inflammation, but suppressed lung defense responses after infection. More chronic inhalation studies are needed to further examine the immune effects and to elucidate the possible mechanisms of the suppressed lung defense response to infection associated with the inhalation of MS welding fume.     

Effect of short-term stainless steel welding fume inhalation exposure on lung inflammation, injury, and defense responses in rats

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(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 5x10(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 generated fume to be 0.255 microm. 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.     

Inhalation toxicity of potassium octatitanate fibers (TISMO) in rats following 13 weeks of aerosol exposure

One hundred and forty male and 140 female rats were divided into 1 control and 3 test groups of 35 rats each, per sex, and exposed by whole-body inhalation to test compound at target concentrations of 0, 1 mg/m(3) (1700 fibers/cm(3), 123 WHO fibers/cm(3)), 10 mg/m(3) (5900 fibers/cm(3), 952 WHO fibers/cm(3)), and 100 mg/m(3) (112,700 fibers/cm(3), 7440 WHO fibers/cm(3)) for 6 h/day, 5 days/wk for 13 wk. Ten rats from each group were killed after 13 wk of exposure and 13 wk of recovery, respectively, for histopathological evaluation. The other 15 rats from each group were killed to study lung clearance after 91 days of exposure, and approximately 1.5 and 3 mo of recovery following the end of the 13 wk of exposure. The mean fiber length of the chamber atmosphere was 2.8, 2.7, and 2.8 microm, while the mean fiber width was 0.48, 0.48, and 0.45 microm for the 1-, 10-, and 100-mg/m(3) chambers, respectively. In the 1-mg/m(3) (123 WHO fibers/cm(3)) exposure group, inhaled particles were mostly retained in a few fiber-laden alveolar macrophages (AMs) within the alveoli adjacent to alveolar ducts without any adverse tissue response throughout 13 wk of exposure and following 13 wk of recovery. This exposure concentration was considered to be a no-observable-adverse-effect level (NOAEL), since the alveoli containing fiber-laden AMs preserved normal structure. After 13 wk of exposure to 10 mg/m(3) (952 WHO fibers/cm(3)), fiber-laden AMs were mainly retained at the alveoli adjacent to the alveolar ducts. Infrequently, slight fibrotic thickening was observed in the alveolar ducts and adjoining alveoli, with proliferating fibroblasts and hyperplastic Type II pneumocytes, and microgranulomas. Occasionally, trace amounts of collagenous material were deposited in the thickened alveolar ducts and adjoining alveolar walls. In addition, minimal alveolar bronchiolarization was occasionally found in the alveoli adjacent to the terminal bronchioles. The peribronchial lymphoid tissue and thymic lymph nodes contained migrated fiber-laden AMs. After 13 wk of recovery, fiber-laden AMs had mostly disappeared from alveoli located in the peripheral acini, but they localized in the alveolar ducts region, suggesting there was active lung clearance of fibers by the AMs via airways. Thickened alveolar ducts and adjacent alveoli were decreased in thickness, a reversible change manifested by reduction of proliferating Type II pneumocytes and fibroblasts. Collagenized fibrosis was slightly more pronounced in the thickened alveolar ducts and adjoining alveoli. The lung response following 13 wk of exposure to 100 mg/m(3) (7440 WHO fibers/cm(3)) and after 13 wk of recovery was similar to those findings of the 952 WHO fibers/cm(3) group but more pronounced, demonstrating a clear concentration-related response. Alveolar ducts and adjoining alveolar walls in the central acini were irregularly thickened with more frequent evidence of minimal collagenized fibrosis. The lung burden and clearance of fibers were estimated by measuring the total content of titanium (Ti) in the lungs, but high variability of Ti content in control and exposed groups prevented meaningful lung clearance analysis.     

Human nasal mucosal C-reactive protein responses after inhalation of ultrafine welding fume particles: positive correlation to systemic C-reactive protein responses

Abstract

Exposures to occupationally relevant ultrafine, zinc- and copper-containing welding fumes cause inflammatory responses involving systemic IL-6, C-reactive protein (CRP) and serum amyloid A (SAA), all associated with elevated risk of cardiovascular events. We investigated whether the systemic response is preceded by nasal inflammatory reactions. Fifteen nonsmoking male subjects were exposed for 6?h under controlled conditions to zinc-/copper-containing welding fumes (at 2.5?mg/m³) or ambient air control in a randomized order. Nasal secretions were collected before and at 1, 3, 6, 10, and 29?h after exposure. Nasal levels of selected biomarkers were determined by electrochemiluminescent assays and related to their systemic levels. Nasal interferon-γ (IFN-γ) peaked significantly 1?h after start of exposure compared to baseline. Nasal CRP as well as SAA increased significantly at 10 and 29?h compared to baseline. Receiver operating characteristic (ROC) curve analysis for differentiating welding fume from control exposure was performed: The highest area under ROC curve (AUC) values were found for the CRP increases (10, 29?h versus 0?h): AUC?=?0.83, and for IFN-γ increases (1?h versus 0?h): AUC?=?0.92. Nasal and systemic changes of CRP at 29?h revealed a strong correlation (Spearman rank test: increases compared to baseline: r?=?0.815, p?=?0.0022; absolute levels: r?=?0.9, p?=?0.0002). In conclusion, short-term exposure to a zinc- and copper-containing welding fume causes significant increases of inflammatory mediators in nasal mucosal lining fluid. Therefore, measurement of nasal inflammatory mediators may provide a useful means for occupational surveillance of workers exposed to ultrafine metal fume particles.     

Short-term inhalation of stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice

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 between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice.     

Short-term inhalation of stainless steel welding fume causes sustained lung toxicity but no tumorigenesis in lung tumor susceptible A/J mice

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/m(3)×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 between the mouse strains. Monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor-α (TNF-α) were increased in both strains while the B6 also had increased interleukin-6 (IL-6) protein. BAL measures of cytotoxicity and damage were similar between the strains and significantly increased at all time points. Histopathology and tumorigenesis were unremarkable at 78 weeks. In conclusion, GMA-SS welding fume induced a significant and sustained inflammatory response in both mouse strains with no recovery by 28 days. Under our exposure conditions, GMA-SS exposure resulted in no significant tumor development in A/J mice.     

Changes of glycoconjugate expression in nasal respiratory mucosa of rats exposed to welding fumes

To investigate the effects of welding fumes on the glycoconjugates in nasal respiratory mucosa, male Sprague-Dawley rats were exposed to manual metal arc stainless steel (MMA-SS) welding fumes at a concentration of 56-76 mg/m(3) total suspended particulate for 2 h/day in an inhalation chamber for 90 days. During the exposure period, the experimental animals were sacrificed after 2 h and 15, 30, 60, and 90 days of exposure; then sections were examined using lectin histochemistry. Some remarkable changes, such as destroyed cilia, desquamation and mucification of epithelial cells, and destruction of nasal septal glands, were seen in the welding fume-exposed groups. Specific changes in the lectin binding patterns were also observed in the welding fume-exposed rats. The Ricinus communis agglutinin-I (RCA-I) staining of the cilia and columnar cells increased slightly when compared with the unexposed rats. The RCA-I and Ulex europaeus agglutinin-I (UEA-I) staining of the goblet cells also increased as the exposure continued. The mucigenous epithelial cells reacted with Bandeiraea simplicifolia lectin-I (BSL-I), RCA-I, and succinylated wheat germ agglutinin A (sWGA) after 15 days of exposure, which was not visible in the control group. The dorsal septal glands exhibited an affinity with peanut agglutinin (PNA), BSL-I, and RCA-I, which was also not visible in the control group. The affinity for Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), PNA, sWGA, BSL-I, and UEA-I in the ventral septal glands of the welding fume-exposed groups tended to increase, whereas the concanavalin A (Con A) reactivity in the dorsal septal glands decreased slightly. In conclusion, it was assumed that the changes in the glycoconjugate residues in the nasal respiratory mucosa of the welding fume-exposed rats represented important components of defense mechanisms against the toxicants in the welding fumes.     

Persistence of deposited metals in the lungs after stainless steel and mild steel welding fume inhalation in rats

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/m³ 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.     

Soluble transition metals cause the pro-inflammatory effects of welding fumes in vitro

Epidemiological studies have consistently reported a higher incidence of respiratory illnesses such as bronchitis, metal fume fever (MFF), and chronic pneumonitis among welders exposed to high concentrations of metal-enriched welding fumes. Here, we studied the molecular toxicology of three different metal-rich welding fumes: NIMROD 182, NIMROD c276, and COBSTEL 6. Fume toxicity in vitro was determined by exposing human type II alveolar epithelial cell line (A549) to whole welding fume, a soluble extract of fume or the "washed" particulate. All whole fumes were significantly toxic to A549 cells at doses >63 microg ml(-1) (TD 50; 42, 25, and 12 microg ml(-1), respectively). NIMROD c276 and COBSTEL 6 fumes increased levels of IL-8 mRNA and protein at 6 h and protein at 24 h, as did the soluble fraction alone, whereas metal chelation of the soluble fraction using chelex beads attenuated the effect. The soluble fraction of all three fumes caused a rapid depletion in intracellular glutathione following 2-h exposure with a rebound increase by 24 h. In addition, both nickel based fumes, NIMROD 182 and NIMROD c276, induced significant reactive oxygen species (ROS) production in A549 cells after 2 h as determined by DCFH fluorescence. ICP analysis confirmed that transition metal concentrations were similar in the whole and soluble fractions of each fume (dominated by Cr), but significantly less in both the washed particles and chelated fractions. These results support the hypothesis that the enhanced pro-inflammatory responses of welding fume particulates are mediated by soluble transition metal components via an oxidative stress mechanism.     

Alterations in welding process voltage affect the generation of ultrafine particles, fume composition, and pulmonary toxicity

The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m3 (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile.     

Alterations in welding process voltage affect the generation of ultrafine particles,fume composition,and pulmonary toxicity

Abstract

The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m³ (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile.     

Health effects of welding

Many of the epidemiology studies performed are difficult to compare because of differences in worker populations, industrial settings, welding techniques, duration of exposure, and other occupational exposures besides welding fumes. Some studies were conducted in carefully controlled work environments, others during actual workplace conditions, and some in laboratories. Epidemiology studies have shown that a large number of welders experience some type of respiratory illness. Respiratory effects seen in full-time welders have included bronchitis, airway irritation, lung function changes, and a possible increase in the incidence of lung cancer. Pulmonary infections are increased in terms of severity, duration, and frequency among welders. Although epidemiological studies have demonstrated an increase in pulmonary illness after exposure to welding fumes, little information of the causality, dose-response, and possible underlying mechanisms regarding the inhalation of welding fumes exists. Even less information is available about the neurological, reproductive, and dermal effects after welding fume exposure. Moreover, carcinogenicity and short-term and long-term toxicology studies of welding fumes in animals are lacing or incomplete. Therefore, an understanding of possible adverse health effects of exposure to welding fumes is essential to risk assessment and the development of prevention strategies and will impact a large population of workers.     

Inhalation exposure of gas-metal arc stainless steel welding fume increased atherosclerotic lesions in apolipoprotein E knockout mice

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 40 mg/m³ for 3 h/day for ten days (∼8.26 μg 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.     

INHALATION TOXICITY OF POTASSIUM OCTATITANATE FIBERS (TISMO) IN RATS FOLLOWING 13 WEEKS OF AEROSOL EXPOSURE

One hundred and forty male and 140 female rats were divided into 1 control and 3 test groups of 35 rats each, per sex, and exposed by whole-body inhalation to test compound at target concentrations of 0, 1 mg/m³ (1700 fibers/cm³, 123 WHO fibers/cm³), 10 mg/m³ (5900 fibers/cm³, 952 WHO fibers/cm³), and 100 mg/m³ (112,700 fibers/cm³, 7440 WHO fibers/cm³) for 6 h/day, 5 days/wk for 13 wk. Ten rats from each group were killed after 13 wk of exposure and 13 wk of recovery, respectively, for histopathological evaluation. The other 15 rats from each group were killed to study lung clearance after 91 days of exposure, and approximately 1.5 and 3 mo of recovery following the end of the 13 wk of exposure. The mean fiber length of the chamber atmosphere was 2.8, 2.7, and 2.8 µm, while the mean fiber width was 0.48, 0.48, and 0.45 µm for the 1-, 10-, and 100-mg/m³ chambers, respectively. In the 1-mg/m³ (123 WHO fibers/cm³) exposure group, inhaled particles were mostly retained in a few fiberladen alveolar macrophages (AMs) within the alveoli adjacent to alveolar ducts without any adverse tissue response throughout 13 wk of exposure and following 13 wk of recovery. This exposure concentration was considered to be a no-observable-adverse-effect level (NOAEL), since the alveoli containing fiber-laden AMs preserved normal structure. After 13 wk of exposure to 10 mg/m³ (952 WHO fibers/cm³), fiber-laden AMs were mainly retained at the alveoli adjacent to the alveolar ducts. Infrequently, slight fibrotic thickening was observed in the alveolar ducts and adjoining alveoli, with proliferating fibroblasts and hyperplastic Type II pneumocytes, and microgranulomas. Occasionally, trace amounts of collagenous material were deposited in the thickened alveolar ducts and adjoining alveolar walls. In addition, minimal alveolar bronchiolarization was occasionally found in the alveoli adjacent to the terminal bronchioles. The peribronchial lymphoid tissue and thymic lymph nodes contained migrated fiber-laden AMs. After 13 wk of recovery, fiber-laden AMs had mostly disappeared from alveoli located in the peripheral acini, but they localized in the alveolar ducts region, suggesting there was active lung clearance of fibers by the AMs via airways. Thickened alveolar ducts and adjacent alveoli were decreased in thickness, a reversible change manifested by reduction of proliferating Type II pneumocytes and fibroblasts. Collagenized fibrosis was slightly more pronounced in the thickened alveolar ducts and adjoining alveoli. The lung response following 13 wk of exposure to 100 mg/m³ (7440 WHO fibers/cm³) and after 13 wk of recovery was similar to those findings of the 952 WHO fibers/cm³ group but more pronounced, demonstrating a clear concentration-related response. Alveolar ducts and adjoining alveolar walls in the central acini were irregularly thickened with more frequent evidence of minimal collagenized fibrosis. The lung burden and clearance of fibers were estimated by measuring the total content of titanium (Ti) in the lungs, but high variability of Ti content in control and exposed groups prevented meaningful lung clearance analysis.     

Development and characterization of a resistance spot welding aerosol generator and inhalation exposure system

Abstract

Limited information exists regarding the health risks associated with inhaling aerosols that are generated during resistance spot welding of metals treated with adhesives. Toxicology studies evaluating spot welding aerosols are non-existent. A resistance spot welding aerosol generator and inhalation exposure system was developed. The system was designed by directing strips of sheet metal that were treated with an adhesive to two electrodes of a spot welder. Spot welds were made at a specified distance from each other by a computer-controlled welding gun in a fume collection chamber. Different target aerosol concentrations were maintained within the exposure chamber during a 4-h exposure period. In addition, the exposure system was run in two modes, spark and no spark, which resulted in different chemical profiles and particle size distributions. Complex aerosols were produced that contained both metal particulates and volatile organic compounds (VOCs). Size distribution of the particles was multi-modal. The majority of particles were chain-like agglomerates of ultrafine primary particles. The submicron mode of agglomerated particles accounted for the largest portion of particles in terms of particle number. Metal expulsion during spot welding caused the formation of larger, more spherical particles (spatter). These spatter particles appeared in the micron size mode and accounted for the greatest amount of particles in terms of mass. With this system, it is possible to examine potential mechanisms by which spot welding aerosols can affect health, as well as assess which component of the aerosol may be responsible for adverse health outcomes.     

Short-Term Inhalation Exposure to Mild Steel Welding Fume had no Effect on Lung Inflammation and Injury but did Alter Defense Responses to Bacteria in Rats

Many workers worldwide are continually exposed to complex aerosols generated from welding processes. The objective was to assess the effect of inhalation exposure to mild steel (MS) welding fume on lung injury, inflammation, and defense responses. Male Sprague-Dawley rats were exposed to MS fume at a concentration of 40 mg/m³ × 3 h/day × 3 or 10 days using a robotic welding fume generator. Controls were exposed to filtered air. To assess lung defense responses, a group of animals were intratracheally inoculated with 5 × 10⁴ Listeria monocytogenes 1 day after the last daily exposure. Welding particles were collected during exposure, and chemical composition and particle size were determined. After exposure, lung injury, inflammation, and host defense (bacterial clearance) were measured. The particles were composed of iron (80.6 %) and manganese (14.7 %) with a mass median aerodynamic diameter of 0.31 μ m. No significant difference was observed in lung injury or inflammation after MS fume inhalation at 1, 4, and 11 days after the last exposure. However, there were significantly more bacteria at 3 days after infection in the lungs of the animals exposed to MS fume compared to air controls. Acute exposure of rats to MS fume had no effect on injury and inflammation, but suppressed lung defense responses after infection. More chronic inhalation studies are needed to further examine the immune effects and to elucidate the possible mechanisms of the suppressed lung defense response to infection associated with the inhalation of MS welding fume.     

Effect of welding fume solubility on lung macrophage viability and function in vitro

It was shown previously that fumes generated from stainless steel (SS) welding induced more pneumotoxicity and were cleared from the lungs at a slower rate than fumes collected from mild steel (MS) welding. These differences in response may be attributed to the metal composition of SS and MS welding fumes. In this study, fumes with vastly different metal profiles were collected during gas metal arc (GMA) or flux-covered manual metal arc (MMA) welding using two different consumable electrodes, SS or MS. The collected samples were suspended in saline, incubated for 24 h at 37 degrees C, and centrifuged. The supernatant (soluble components) and pellets (insoluble particulates) were separated, and their effects on lung macrophage viability and the release of reactive oxygen species (ROS) by macrophages were examined in vitro. The soluble MMA-SS sample was shown to be the most cytotoxic to macrophages and to have the greatest effect on their function as compared to the GMA-SS and GMA-MS fumes. Neither the soluble nor insoluble forms of the GMA-MS sample had any marked effect on macrophage viability. The flux-covered MMA-SS fume was found to be much more water soluble as compared to either the GMA-SS or the GMA-MS fumes. The soluble fraction of the MMA-SS samples was comprised almost entirely of Cr. The small fraction of the GMA-MS sample that was soluble contained Mn with little Fe, while a more complex mixture was observed in the soluble portion of the GMA-SS sample, which contained Mn, Ni, Fe, Cr, and Cu. Data show that differences in the solubility of welding fumes influence the viability and ROS production of macrophages. The presence of soluble metals, such as Fe, Cr, Ni, Cu, and Mn, and the complexes formed by these different metals are likely important in the pulmonary responses observed after welding fume exposure.     

Changes of Glycoconjugate Expression in Nasal Respiratory Mucosa of Rats Exposed to Welding Fumes

To investigate the effects of welding fumes on the glycoconjugates in nasal respiratory mucosa, male Sprague-Dawley rats were exposed to manual metal arc stainless steel (MMA-SS) welding fumes at a concentration of 56–76 mg/m³ total suspended particulate for 2 h/day in an inhalation chamber for 90 days. During the exposure period, the experimental animals were sacrificed after 2 h and 15, 30, 60, and 90 days of exposure; then sections were examined using lectin histochemistry. Some remarkable changes, such as destroyed cilia, desquamation and mucification of epithelial cells, and destruction of nasal septal glands, were seen in the welding fume-exposed groups. Specific changes in the lectin binding patterns were also observed in the welding fume-exposed rats. The Ricinus communis agglutinin-I (RCA-I) staining of the cilia and columnar cells increased slightly when compared with the unexposed rats. The RCA-I and Ulex europaeus agglutinin-I (UEA-I) staining of the goblet cells also increased as the exposure continued. The mucigenous epithelial cells reacted with Bandeiraea simplicifolia lectin-I (BSL-I), RCA-I, and succinylated wheat germ agglutinin A (sWGA) after 15 days of exposure, which was not visible in the control group. The dorsal septal glands exhibited an affinity with peanut agglutinin (PNA), BSL-I, and RCA-I, which was also not visible in the control group. The affinity for Dolichos biflorus agglutinin (DBA), soybean agglutinin (SBA), PNA, sWGA, BSL-I, and UEA-I in the ventral septal glands of the welding fume-exposed groups tended to increase, whereas the concanavalin A (Con A) reactivity in the dorsal septal glands decreased slightly. In conclusion, it was assumed that the changes in the glycoconjugate residues in the nasal respiratory mucosa of the welding fume-exposed rats represented important components of defense mechanisms against the toxicants in the welding fumes.     

Lung tumor production and tissue metal distribution after exposure to manual metal ARC-stainless steel welding fume in A/J and C57BL/6J mice

Stainless steel welding produces fumes that contain carcinogenic metals. Therefore, welders may be at risk for the development of lung cancer, but animal data are inadequate in this regard. Our main objective was to examine lung tumor production and histopathological alterations in lung-tumor-susceptible (A/J) and -resistant C57BL/6J (B6) mice exposed to manual metal arc-stainless steel (MMA-SS) welding fume. Male mice were exposed to vehicle or MMA-SS welding fume (20 mg/kg) by pharyngeal aspiration once per month for 4 mo. At 78 wk postexposure, gross tumor counts and histopathological changes were assessed and metal analysis was done on extrapulmonary tissue (aorta, heart, kidney, and liver). At 78 wk postexposure, gross lung tumor multiplicity and incidence were unremarkable in mice exposed to MMA-SS welding fume. Histopathology revealed that only the exposed A/J mice contained minimal amounts of MMA-SS welding fume in the lung and statistically increased lymphoid infiltrates and alveolar macrophages. A significant increase in tumor multiplicity in the A/J strain was observed at 78 wk. Metal analysis of extrapulmonary tissue showed that only the MMA-SS-exposed A/J mice had elevated levels of Cr, Cu, Mn, and Zn in kidney and Cr in liver. In conclusion, this study further supports that MMA-SS welding fume does not produce a significant tumorigenic response in an animal model, but may induce a chronic lung immune response. In addition, long-term extrapulmonary tissue alterations in metals in the susceptible A/J mouse suggest that the adverse effects of this fume might be cumulative.