Interstitial lung disease related to occupational hard metal exposure: two case reports.

BACKGROUND: Hard metal lung disease (HMLD) is a relatively less known occupational interstitial lung disease, and instances of HMLD resulting from para-occupational exposure are rarely reported. CASE PRESENTATION: This paper presents two cases of interstitial lung disease caused by exposure to hard metal. The first case involves a 37-year-old Taiwanese man who had worked at a grinder station for hard metal materials for 12 years without respiratory protective equipment. He experienced a dry cough and exertional dyspnea, and his chest imaging and pathology findings were consistent with the features of usual interstitial pneumonia. Analysis of his lung tissue revealed the presence of tungsten and cobalt. The second case involves a 68-year-old Taiwanese woman, the mother of the first patient, who had hand-washed her son's workwear. She experienced a dry cough and had similar imaging findings to her son. After her son left his job, they both exhibited improved symptoms and lung functions with nintedanib treatment. These findings suggest a diagnosis of HMLD and interstitial lung disease resulting from para-occupational exposure to hard metal dust. CONCLUSIONS: The diagnosis of HMLD relies on obtaining a detailed occupational exposure history. If HMLD is diagnosed, discontinuing exposing to hard metal dusts can lead to improved lung function.

MiADMSA abrogates sodium tungstate-induced oxidative stress in rats.

Tungsten (W) and its compounds have emerged as a relatively new area of environmental health concern in the last decade. Tungsten is environmentally benign due to its increasing use in armour-piercing munitions and as a replacement for lead in other ammunition. It has also been identified in various hazardous waste sites and therefore been proposed for inclusion in the Environmental Protection Agency National Priorities List. The major objective of this study was to evaluate the therapeutic efficacy of orally administered monoisoamyl 2, 3-dimercaptosuccinic acid (MiADMSA) against tungstate induced oxidative injury in blood, liver and kidneys of male Wistar rats. MiADMSA, a thiol chelator has gained wide recognition recently as a future chelating drug of choice specifically for arsenic and was chosen for this study as tungstate ions too have an affinity toward the -SH group thus, being less bioavailable in the body. We determined the effects of MiADMSA (50 mg/kg, p.o.) against sodium tungstate (500 ppm in drinking water, daily for 28 days) induced biochemical changes indicative of oxidative stress in blood, and other soft tissues of of male Wistar rats. Tungsten exposure led to an increased levels of Reactive Oxygen Species (ROS) in liver, kidney, spleen and blood accompanied also by an increase in TBARS levels. The GSH: GSSG ratio also showed a decrease on sodium tungstate intoxication. Treatment with MiADMSA restored most of the sodium tungstate-induced alterations in the biomarkers suggestive of oxidative stress. These preliminary results led us to conclude that sub-acute exposure to tungstate-induced oxidative stress could be effectively reduced by the administration of MiADMSA and thus might be a promising antidote for studying in detail its efficacy in reducing body tungstate burden and its excretion post tungstate exposure.

Effect of the Photocatalyst under Visible Light Irradiation in SARS-CoV-2 Stability on an Abiotic Surface.

There is a worldwide attempt to develop prevention strategies against SARS-CoV-2 transmission. Here we examined the effectiveness of tungsten trioxide (WO3)-based visible light-responsive photocatalyst on the inactivation of SARS-CoV-2 under different temperatures and exposure durations. The viral titer on the photocatalyst-coated glass slides decreased from 5.93 ± 0.38 logTCID50 /mL to 3.05 ±. 25 logTCID50/mL after exposure to 3,000 lux of the visible light irradiation for 6h at 20℃. On the other hand, lighting without the photocatalyst, or the photocatalyst-coat without lighting retained viral stability. Immunoblotting and electron microscopic analyses showed the reduced amounts of spike protein on the viral surface after the photocatalyst treatment. Our data suggest a possible implication of the photocatalyst on the decontamination of SARS-CoV-2 in indoor environments, thereby preventing indirect viral spread.

Tungsten accumulates in the intervertebral disc and vertebrae stimulating disc degeneration and upregulating markers of inflammation and pain.

Tungsten is incorporated in many industrial goods, military applications and medical devices due to its ability to impart flexibility, strength and conductance to materials. Emerging evidence has questioned the safety of tungsten exposure as studies have demonstrated it can promote tumour formation, induce pulmonary disease and alter immune function. Although tungsten is excreted from the body it can accumulate in certain organs such as the brain, colon, liver, kidneys, spleen and bones, where most of the bioaccumulation occurs. Whether prolonged tungsten exposure leads to accumulation in other tissues is unknown. The present study demonstrated that mice exposed to 15 ppm sodium tungstate for 4 weeks in their drinking water showed comparable accumulation in both the bony vertebrae and intervertebral discs (IVDs). Lumbar IVD height was significantly reduced in tungsten-exposed mice and accompanied by decreased proteoglycan content and increased fibrosis. In addition to catabolic enzymes, tungsten also increased the expression of the inflammatory cytokines IL-1ß and tumour necrosis factor (TNF)-α as well as the neurotrophic factors nerve growth factor (NGF) and brain-derived nerve factor (BDNF) in IVD cells. Tungsten significantly increased the presence of nociceptive neurons at the endplates of IVDs as observed by the expression of calcitonin gene-related peptide (CGRP) and anti-protein gene product 9.5 (PGP9.5) in endplate vessels. The present study provided evidence that tungsten may enhance disc degeneration and fibrosis as well as increase the expression of markers for pain. Therefore, tungsten toxicity may play a role in disc degeneration disease.

[Investigation of contact dermatitis caused by hard metal dust].

Objective: To investigate the incidence of contact dermatitis among workers in cemented carbide production enterprises. Methods: From October 1997 to October 2017, an occupational epidemiological survey was conducted on a large-scale cemented carbide production enterprise, and occupational health examinations were conducted for employees. 152 people were exposed to hard metal dust (hard metal raw material dust and alloy dust) . The employees in the work group were contact groups, and 142 employees in the non-dusting operation of the company were in the control group. A detailed retrospective survey of hard metal production workers with contact dermatitis history in the two groups was conducted to analyze the risk factors of contact dermatitis exposure to hard metal dust. Results: The incidence of allergic diseases in the exposed group was significantly higher than that in the control group. The difference was statistically significant (χ(2)=23.793, P<0.05) . The incidence of contact dermatitis in the exposed group was significantly higher than that in the control group. The difference was statistically significant (χ(2)=24.659, P<0.05) ; the changes of contact dermatitis in the contact group were mainly allergic contact dermatitis, and some showed irritative contact dermatitis; the operator had respiratory symptoms (including work-related nasal congestion, cough, wheezing) , difficulty breathing may be the influencing factors of contact dermatitis (RR=2.60, 95%CI: 1.10-6.20, P<0.05) . Conclusion: Hard metal alloy enterprises are exposed to hard metal dust. The incidence of contact dermatitis is high in workers, and the occurrence of contact dermatitis may be associated with those with respiratory symptoms.

Hard Metal Lung Disease with Favorable Response to Corticosteroid Treatment: A Case Report and Literature Review.

Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.

Investigating Serious Adverse Drug Reactions in Patients Receiving Erythropoiesis-Stimulating Agents: A Root Cause Analysis Using the "ANTICIPATE" Framework.

BACKGROUND: Unexpected serious adverse drug reactions (sADRs) affecting patients with chronic kidney disease (CKD) who received erythropoiesis-stimulating agents were identified by study co-authors. These included pure red cell aplasia (PRCA) after administration of the Eprex formulation of epoetin or the epoetin biosimilar HX575 and fatal anaphylaxis associated with peginesatide, an erythropoietin receptor agonist. We developed and applied a structured framework to describe these sADRs, including root cause analyses and eradication efforts. METHODS: A 10-step framework termed "ANTICIPATE," focusing on signal identification, incidence, causality, and eradication guided our evaluations. RESULTS: Initial cases were identified by a hematologist (Eprex), clinical study monitors (HX575), and 4 nurses (peginesatide). The number of persons with individual ADRs was 13 PRCA cases for epoetin, 2 antibody-mediated PRCA cases for HX575, and 5 fatal anaphylaxis cases for peginesatide. Initial incidence estimates per 1000 treated persons were 0.27 for Eprex-associated PRCA, 11 for HX575-associated PRCA, and 0.38 for peginesatide fatalities. Likely causes were subcutaneous administration of epoetin formulated with polysorbate 80 (Eprex), tungsten leaching from pins included in product syringes (HX575), and inclusion of a phenol stabilizer (peginesatide). Eradication strategies included restricting Eprex administration to the intravenous route, excluding tungsten from HX575 syringes, and for peginesatide, proposed eradication was to return to single-dose vials without preservatives. CONCLUSION: Although the number of cases of each sADR was small, eradication was successful for 2 sADRs, and a proposed eradication was developed for a third sADR. The structured framework used to describe the above 3 sADRs in patients with CKD can also be used in other clinical settings.

Biomarkers of exposure to stainless steel tungsten inert gas welding fumes and the effect of exposure on exhaled breath condensate.

The respiratory tract is the main target organ of the inhaled hexavalent chromium (Cr-VI) and nickel (Ni) contained in stainless steel (SS) welding fumes (WFs). The aim of this study was to investigate the Cr and Ni content of the exhaled breath condensate (EBC) of SS tungsten inert gas (TIG) welders, and relate their concentrations with oxidative stress and inflammatory biomarkers. EBC and urine from 100 SS TIG welders were collected pre-(T0) and post-shift (T1) on a Friday, and pre-shift (T2) on the following Monday morning. Both EBC and urinary Cr concentrations were higher at T1 (0.08 µg/L and 0.71 µg/g creatinine) and T0 (0.06 µg/L and 0.74 µg/g creatinine) than at T2 (below the limit of detection [LOD] and 0.59 µg/g creatinine), and EBC Ni concentrations generally remained

The use of tungsten as a chronically implanted material.

This review paper shows that tungsten should not generally be used as a chronically implanted material. The metal has a long implant history, from neuroscience, vascular medicine, radiography, orthopaedics, prosthodontics, and various other fields, primarily as a result of its high density, radiopacity, tensile strength, and yield point. However, a crucial material criterion for chronically implanted metals is their long-term resistance to corrosion in body fluids, either by inherently noble metallic surfaces, or by protective passivation layers of metal oxide. The latter is often assumed for elemental tungsten, with references to its 'inertness' and 'stability' common in the literature. This review argues that in the body, metallic tungsten fails this criterion, and will eventually dissolve into the soluble hexavalent form W6+, typically represented by the orthotungstate [Formula: see text] (monomeric tungstate) anion. This paper outlines the metal's unfavourable corrosion thermodynamics in the human physiological environment, the chemical pathways to either metallic or metal oxide dissolution, the rate-limiting steps, and the corrosion-accelerating effects of reactive oxidising species that the immune system produces post-implantation. Multiple examples of implant corrosion have been reported, with failure by dissolution to varying extents up to total loss, with associated emission of tungstate ions and elevated blood serum levels measured. The possible toxicity of these corrosion products has also been explored. As the field of medical implants grows and designers explore novel solutions to medical implant problems, the authors recommend the use of alternative materials.

Tungsten or Wolfram: Friend or Foe?

Tungsten or wolfram was regarded for many years as an enemy within the tin smelting and mining industry, because it conferred impurity or dirtiness in tin mining. However, later it was considered an amazing metal for its strength and flexibility, together with its diamond like hardness and its melting point which is the highest of any metal. It was first believed to be relatively inert and an only slightly toxic metal. Since early 2000, the risk exerted by tungsten alloys, its dusts and particulates to induce cancer and several other adverse effects in animals as well as humans has been highlighted from in vitro and in vivo experiments. Thus, it becomes necessary to take a careful look at all the most recent data reported in the scientific literature, covering the years 2001-2016. In fact, the findings indicate that much more attention should be devoted to thoroughly investigate the toxic effects of tungsten and the involved mechanisms of tungsten metal or tungsten metal ions.

Mortality Among Hardmetal Production Workers: German Historical Cohort Study.

OBJECTIVE: The aim of this study was to investigate a cohort in German hardmetal industry, especially relationship between exposures to cobalt, with and without tungsten, and risks of total and cause-specific mortality. METHODS: The cohort comprises blue-collar workers at three German plants who were employed in hardmetal processing. Individual cumulative exposures and long-term average concentrations were estimated for cobalt, nickel, tungsten, respirable, and inhalable dust. Standardized mortality ratios (SMRs) were calculated for external comparisons. Time-dependent multivariable Cox models were performed for internal analyses. RESULTS: Elevated SMRs were found for all-cause, heart diseases, and nonmalignant respiratory diseases mortality, but not for lung cancer. Internal analyses did not show increased risks for any endpoints, and no exposure-response relationship was indicated. CONCLUSIONS: This study does not provide evidence for elevated lung cancer risks. Methodologic limitations, incomplete ascertainment of death causes in particular, impede conclusions about exposure effects.

Mortality Among Hardmetal Production Workers: The Swedish Cohort.

BACKGROUND: The mortality pattern was determined in a cohort of 16,999 white and blue-collar workers in the Swedish hardmetal industry, particularly for cobalt exposure and lung cancer. METHODS: The mortality follow-up analysis in the Swedish Mortality register covered the period from 1952 to 2012. The exposure measures were ever/never exposed, duration of exposure, cumulative, and mean cobalt concentrations. RESULTS: The mortality of all causes was significantly increased, highly associated with the short-term employed workers. A negative exposure-response was found for lung cancer and duration of exposure. An exposure-response was determined for cumulative and mean cobalt exposures analyzed by quartiles, but not for exposure classes. Internal comparison analysis using proportional hazard showed no exposure-response. CONCLUSIONS: The cohort lung cancer mortality showed no correlation to cobalt, nickel, or tungsten exposure.

Mortality Among Hardmetal Production Workers: US Cohort and Nested Case-Control Studies.

OBJECTIVES: To evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer. METHODS: Subjects were 7304 workers ever employed in one of eight US plants from 1952 to 2008. Vital status through 2012 was determined for 97% of subjects and cause of death for 98.3% of 1087 deaths. We computed standardized mortality ratios (SMRs) and evaluated exposure-response via relative risk regression analysis. RESULTS: We observed overall deficits in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer. CONCLUSIONS: We found no evidence that exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in the US hardmetal industry increases mortality risks from any other causes of death.

Mortality Among Hardmetal Production Workers: Pooled Analysis of Cohort Data From an International Investigation.

OBJECTIVES: Based on a pooled analysis of data from an international study, evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer. METHODS: Study members were 32,354 workers from three companies and 17 manufacturing sites in five countries. We computed standardized mortality ratios and evaluated exposure-response via relative risk regression analysis. RESULTS: Among long-term workers, we observed overall deficits or slight excesses in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer. CONCLUSIONS: We found no evidence that duration, average intensity, or cumulative exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in these facilities increased mortality risks from any other causes of death.

Mortality Among Hardmetal Production Workers: Swedish Measurement Data and Exposure Assessment.

BACKGROUND: Mortality pattern was determined in a cohort of 16,999 white and blue-collar workers in the Swedish hardmetal industry. Exposure assessment for cobalt is presented. METHODS: A historical database (1970 to 2012) of personal and area measurements of cobalt, tungsten, and nickel in the Swedish hardmetal industry was created. Log linear and exponential modeling of cobalt concentrations based on time period, job, and site was performed, and cumulative and mean exposures were calculated. RESULTS: Some 37% of the personal cobalt measurements exceeded 0.02 mg/m, mostly for powder production, pressing, and shaping. The log linear regression showed statistical differences (P < 0.05) between sites, time periods, and jobs. Some 1.6% of the cobalt cumulative exposures for blue-collar workers exceeded 0.4 mg/m years. CONCLUSION: Low levels of cumulative and mean exposures were determined.

Cancer Incidence Among Hardmetal Production Workers: The Swedish Cohort.

: The cancer incidence was determined for 3713 workers from three plants from 1958 to 2011. The exposure measures were ever/never exposed, duration, cumulative, and mean cobalt concentrations.The incidence of all malignant neoplasms was increased at one plant, but standardized incidence ratio (SIR) was 0.96 for all workers. Lung cancer incidence was increased for all workers, SIR 1.38 (1.01 to 1.85). The lung cancer incidence was associated with shorter employment time and showed no exposure-response. There was decreased incidence for skin cancer. Increased lip cancer incidence found at one of the production plants might be related to diagnostic intensity.Lung cancer incidence showed no correlation to cobalt exposure based on internal comparison. The increased SIR for all workers might be associated with other factors.

Biocompatibility evaluation and corrosion resistance of tungsten added Co-30Cr-4Mo-1Ni alloy.

Biomaterials are continuously being developed to overcome the drawbacks of existing materials and provide improved function in artificial organs. Currently Co-Cr based alloys are used in many medical applications such as hip and knee implants which still require modification to better perform. In this article, therefore, the influence of tungsten allying element on electrochemical corrosion resistance and biocompatibility behaviour of a recently developed Co-30Cr-4Mo-1Ni alloy composition were investigated. The tungsten modified alloys were prepared by using a high temperature vertical vacuum casting technique at five different weight percentages (0-4wt.% tungsten). The electrochemical corrosion behaviour of all the samples under NaCl solution was studied by using potentiodynamic scan method. The corrosion characteristics were investigated in terms of corrosion potential (Ecorr) and corrosion current density (Icorr). From the results of the analysis, it was observed that out of all samples, an alloy with 2wt.% of tungsten in composition (i.e. Co-30Cr-4Mo-1Ni-2W) exhibited better corrosion resistance. Furthermore, histopathological evaluations in subcutaneous tissue were performed in rats according to the standard ISO 10993 to examine the biocompatibility of the prepared samples. The results showed no evidence of inflammatory cell migration, no epidermal necrosis, no vacuolar degeneration of basal cell, no adnexal atrophy and vesicle formation of any samples. The obtained findings indicate that Co-30Cr-4Mo-1Ni-2W can be used in biomedical applications including femoral component of hip and knee implants.

[Determination of tungsten and cobalt in the air of workplace by ICP-OES].

Objective: To establish the inductively coupled plasma optical emission spectrometry (ICP-OES) method for determination of cobalt and tungsten in the air of workplace. Methods: The cobalt and tungsten were collected by filter membrane and then digested by nitric acid, inductively coupled plasma optical emission spectrometry (ICP-OES) was used for the detection of cobalt and tungsten. Results: The linearity of tungsten was good at the range of 0.01-1 000 µg/ml with a correlation coefficient of 0.999 9, the LOD and LOQ were 0.006 7 µg/ml and 0.022 µg/ml, respectively. The recovery was ranged from 98%-101%, the RSD of intra-and inter-batch precision were 1.1%-3.0% and 2.1%-3.8%, respectively. The linearity of cobalt was good at the range of 0.01-100 µg/ml with a correlation coefficient of 0.999 9, the LOD and LOQ were 0.001 2 µg/ml and 0.044 µg/ml, respectively. The recovery was ranged from 95%-97%, the RSD of intra-and inter-batch precision were 1.1%-2.4% and 1.1%-2.9%, respectively. The sampling efficiency of tungsten and cobalt were higher than 94%. Conclusion: The linear range, sensitivity and precision of the method was suitable for the detection of tungsten and cobalt in the air of workplace.

Mortality Among Hardmetal Production Workers: A Retrospective Cohort Study in the Austrian Hardmetal Industry.

OBJECTIVE: This study retrospectively investigates causes of death among workers of a hardmetal plant in Austria. METHODS: A retrospective cohort was formed of 1965 workers still employed in or after 1970. Follow-up was until end of 2014 based on national databases. Cobalt exposure was assessed through industrial hygiene data and urine analyses. Cox proportional hazards models were calculated for selected causes of death. RESULTS: During 45,598 years of observation in total 177 deaths were observed. Forty-nine workers died from any cancer, 10 from lung cancer, and three from chronic obstructive pulmonary disease. Only the latter showed a significant association with cumulative exposure. CONCLUSIONS: Although this is a young study population with little power to detect subtle effects, at least it does not indicate a pronounced cancer risk among tungsten carbide workers due to cobalt.

Mortality Among Hardmetal Production Workers: Occupational Exposures.

OBJECTIVE: To generate quantitative exposure estimates for use in retrospective occupational cohort mortality studies of the hardmetal industry. METHODS: Job-exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over the time period 1952 to 2014. The JEMs consisted of job class categories, based on job titles and processes performed, and exposure estimates calculated from available company industrial hygiene measurements. RESULTS: Exposure intervals of one-half order magnitude were established for all three agents. Eight job classes had significantly decreasing time trends for cobalt exposure; no significant time trends were detected for tungsten or nickel exposures. CONCLUSIONS: The levels of exposures determined for this study were similar to or lower than those previously reported for the hardmetal industry during the 1952 to 2014 study period.