Relationship between cumulative silica exposure and silicosis: a systematic review and dose-response meta-analysis.

BACKGROUND: Silicosis, a chronic respiratory disease caused by crystalline silica exposure, is a persistent global lung health issue. No systematic review of the relationship between cumulative respirable crystalline silica (RCS) exposure and silicosis exists. UK exposure limits are currently under review. We therefore performed a systematic review and dose-response meta-analysis of this relationship. METHODS: Web of Science, Medline and Embase were searched on 24 February 2023. Studies of radiographic, autopsy or death certificate silicosis, with an estimated average follow-up of over 20 years since first employment, were included. Cumulative silicosis risk methods were compared. The relative risks (RR) of silicosis at increasing cumulative exposures were calculated and used to estimate the absolute risk reduction (ARR). RESULTS: Eight eligible studies, including 10 cohorts, contributed 8792 cases of silicosis among 65 977 participants. Substantial differences in cumulative risk estimates between methodologies exist. Using the same method, we observed higher cumulative silicosis risks among mining compared with non-mining cohorts. A reduction from 4 to 2 mg/m³-years in cumulative RCS exposure corresponded to substantial risk reductions among miners (RR 0.23 (95% CI 0.18 to 0.29, I2=92.9%) with an ARR of 323 (95% CI 298 to 344) per 1000) and non-miners (RR 0.55 (95% CI 0.36 to 0.83, I2=77.0%) with an ARR of 23 (95% CI 9 to 33) per 1000). CONCLUSION: Despite significant heterogeneity, our findings support a reduction in permissible exposure limits from 0.1 mg/m3 to 0.05 mg/m³, particularly among mining populations. Further research is needed among non-miners as only two studies were eligible.

Is exposure to environmental factors associated with a characteristic clinical and laboratory profile in systemic sclerosis? A retrospective analysis.

To identify environmental factors (EF) in a large cohort of patients with systemic sclerosis (SSc) analyzing their clinical and laboratory presentation. A cohort of consecutive patients attended at a single Brazilian SSc outpatient clinic was analyzed regarding EF. Data were analyzed according to clinical, demographic and laboratory characteristics, as well as SSc subtype. In a cohort of 662 patients, 70 (10.6%) had known previous exposure to EF, predominantly organic solvents (51.4%), silica (20%), silicone (12.9%) and pesticides (11.4%). In the SSc cohort, patients with EF had a significantly higher frequency of male gender (p < 0.01), African-Brazilian ethnicity (p = 0.01), myopathy (p = 0.02), and pigmentary disorders (p = 0.04), with shorter disease duration (p = 0.01). When SSc subtypes were analyzed separately, there was positive association with male gender in limited (p < 0.01) and diffuse (p < 0.01) SSc, as well as African-Brazilian ethnicity (p = 0.04), severe interstitial lung disease (p < 0.01), myopathy (p = 0.02) and SD pattern at nailfold capillaroscopy (p = 0.01) in limited SSc, and negative association with esophageal hypomotility (p < 0.01) and ANA positivity (p = 0.02) in diffuse SSc. Multiple regression analyses showed that myopathy was independently associated with previous exposure to EF (OR = 2.09; 95% CI 1.15-3.82), especially silica exposure (OR = 3.09; 95% CI 1.67-5.73). This study showed that SSc patients with previous exposure to EF may have some specific clinical characteristics, mainly a higher frequency of myopathy, also showing more severe ILD, preferably in male and African-Brazilian patients, associated with a lower frequency of ANA positivity.

Effect of nano-sized SiO2 particles on the cognitive function and biochemical response.

Several in vitro studies have convincingly demonstrated that SiO2NPs mediated cytotoxicity, which was dose-, time- and size-dependent. The data on in vivo toxicity of SiO2NPs are even more contradictory. In the present study, we investigated the effects of sub-acute exposure to SiO2-NPs on spatial learning and memory, the biochemical parameters and the histology of organs. Rats were injected intravenously with a single dose of SiO2-NPs (20 mg/kg) during five consecutive days. The analysis of spatial memory in the Morris water maze showed that SiO2-NPs disrupt the cognitive abilities of rats. Moreover, SiO2-NPs could changes the blood counts. However, biochemical markers remained unchanged. Histological examination showed that SiO2-NPs induced pathological changes in rat organs. In this finding NPs were shown to cause granuloma formation and inflammatory cells infiltration in the liver.

Genome-wide DNA methylation analysis in lung fibroblasts co-cultured with silica-exposed alveolar macrophages.

BACKGROUND: Exposure to crystalline silica is considered to increase the risk of lung fibrosis. The primary effector cell, the myofibroblast, plays an important role in the deposition of extracellular matrix (ECM). DNA methylation change is considered to have a potential effect on myofibroblast differentiation. Therefore, the present study was designed to investigate the genome-wide DNA methylation profiles of lung fibroblasts co-cultured with alveolar macrophages exposed to crystalline silica in vitro. METHODS: AM/fibroblast co-culture system was established. CCK8 was used to assess the toxicity of AMs. mRNA and protein expression of collagen I, α-SMA, MAPK9 and TGF-ß1 of fibroblasts after AMs exposed to 100 µg /ml SiO2 for 0-, 24-, or 48 h were determined by means of quantitative real-time PCR, immunoblotting and immunohistochemistry. Genomic DNA of fibroblasts was isolated using MeDIP-Seq to sequence. R software, GO, KEGG and Cytoscape were used to analyze the data. RESULTS: SiO2 exposure increased the expression of collagen I and α-SMA in fibroblasts in co-culture system. Analysis of fibroblast methylome identified extensive methylation changes involved in several signaling pathways, such as the MAPK signaling pathway and metabolic pathways. Several candidates, including Tgfb1 and Mapk9, are hubs who can connect the gene clusters. MAPK9 mRNA expression was significantly higher in fibroblast exposed to SiO2 in co-culture system for 48 h. MAPK9 protein expression was increased at both 24-h and 48-h treatment groups. TGF-ß1 mRNA expression of fibroblast has a time-dependent manner, but we didn't observe the TGF-ß1 protein expression. CONCLUSION: Tgfb1 and Mapk9 are helpful to explore the mechanism of myofibroblast differentiation. The genome-wide DNA methylation profiles of fibroblasts in this experimental silicosis model will be useful for future studies on epigenetic gene regulation during myofibroblast differentiation.

Assessment of respiratory symptoms and lung function values among the brick field workers of West Bengal, India.

Brick manufacturing process releases large amounts of silica dust into the work environment due to the use of silica-containing materials. The main aim of the study was to investigate the impairment of lung function and prevalence of respiratory symptoms among the different groups of brick field workers in comparison with control subjects. A total of 250 brick field workers and 130 unexposed control subjects were randomly selected in which demographic characteristics, respiratory symptoms, and lung function values were recorded. The result showed significantly lower p value (<.001) in lung function and respiratory symptoms among brick field workers when compared with control group. The prevalence of respiratory symptoms was dyspnea (46.8%), phlegm (39.2%), and chest tightness (27.6%). Dust exposure in working environment affected the lung function values and increased the respiratory symptoms among the brick field workers.

Notes from the Field: Update: Silicosis Mortality - United States, 1999-2013.

Silicosis is a potentially fatal but preventable occupational lung disease caused by inhaling respirable crystalline silica (silica). Chronic silicosis, the most common form, occurs after exposure to relatively low silica concentrations for >10 years. Accelerated silicosis occurs after 5-10 years of exposure to higher silica levels, and acute silicosis can occur after only weeks or months of exposure to extremely high silica concentrations. New national mortality data for silicosis have become available since a previous report on silicosis surveillance was published earlier this year. CDC reviewed multiple cause-of-death mortality files from the National Center for Health Statistics to analyze deaths from silicosis (International Classification of Diseases, 10th Revision diagnosis code J62: a pneumoconiosis due to dust containing silica) reported during 1999-2013. Each record lists one underlying cause of death (the disease or injury that initiated the chain of events that led directly and inevitably to death), and up to 20 contributing causes of death (other significant conditions contributing to death but not resulting in underlying cause). Available death certificates from 35 states were reviewed for the period 2004-2006 to identify occupations associated with silicosis among decedents aged 15-44 years. Results indicate that despite substantial progress in eliminating silicosis, silicosis deaths continue to occur. Of particular concern are silicosis deaths in young adults (aged 15-44 years). These young deaths likely reflect higher exposures than those causing chronic silicosis mortality in older persons, some of sufficient magnitude to cause severe disease and death after relatively short periods of exposure. A total of 12 such deaths occurred during 2011-2013, with nine that had silicosis listed as the underlying cause of death.

Silicosis mortality trends and new exposures to respirable crystalline silica - United States, 2001-2010.

Silicosis is a preventable occupational lung disease caused by the inhalation of respirable crystalline silica dust and can progress to respiratory failure and death. No effective specific treatment for silicosis is available; patients are provided supportive care, and some patients may be considered for lung transplantation. Chronic silicosis can develop or progress even after occupational exposure has ceased. The number of deaths from silicosis declined from 1,065 in 1968 to 165 in 2004. Hazardous occupational exposures to silica dust have long been known to occur in a variety of industrial operations, including mining, quarrying, sandblasting, rock drilling, road construction, pottery making, stone masonry, and tunneling operations. Recently, hazardous silica exposures have been newly documented during hydraulic fracturing of gas and oil wells and during fabrication and installation of engineered stone countertops. To describe temporal trends in silicosis mortality in the United States, CDC analyzed annual multiple cause-of-death data for 2001-2010 for decedents aged ≥15 years. During 2001-2010, a total of 1,437 decedents had silicosis coded as an underlying or contributing cause of death. The annual number of silicosis deaths declined from 164 (death rate† = 0.74 per 1 million population) in 2001 to 101 (0.39 per 1 million) in 2010 (p = 0.002). Because of new operations and tasks placing workers at risk for silicosis, efforts to limit workplace exposure to crystalline silica need to be maintained.

Quantitative relationship between silica exposure and lung cancer mortality in German uranium miners, 1946-2003.

BACKGROUND: In 1996 and 2009, the International Agency for Research on Cancer classified silica as carcinogenic to humans. The exposure-response relationship between silica and lung cancer risk, however, is still debated. Data from the German uranium miner cohort study were used to further investigate this relationship. METHODS: The cohort includes 58677 workers with individual information on occupational exposure to crystalline silica in mg m(-3)-years and the potential confounders radon and arsenic based on a detailed job-exposure matrix. In the follow-up period 1946-2003, 2995 miners died from lung cancer. Internal Poisson regression with stratification by age and calendar year was used to estimate the excess relative risk (ERR) per dust-year. Several models including linear, linear quadratic and spline functions were applied. Detailed adjustment for cumulative radon and arsenic exposure was performed. RESULTS: A piecewise linear spline function with a knot at 10 mg m(-3)-years provided the best model fit. After full adjustment for radon and arsenic no increase in risk <10 mg m(-3)-years was observed. Fixing the parameter estimate of the ERR in this range at 0 provided the best model fit with an ERR of 0.061 (95% confidence interval: 0.039, 0.083) >10 mg m(-3)-years. CONCLUSION: The study confirms a positive exposure-response relationship between silica and lung cancer, particularly for high exposures.

Nanomaterials in humans: identification, characteristics, and potential damage.

Nanomaterials are increasingly being used for commercial purposes. However, concerns about the potential risks of exposure to humans have been raised. We previously reported unusual pulmonary disease and death in a group of patients with occupational exposure to spray paint. However, the nanoparticle and chemical composition of the exposure was not fully described. The present study aimed to isolate and identify the nanoparticles observed in the patients' biopsies and report the potential deleterious effects to human lungs using electron microscopy. Using electron microscopy and energy dispersive x-ray analysis, silica nanoparticles were identified and characterized mainly in macrophages, pulmonary microvessels, vascular endothelial cells, microlymphatic vessels, pleural effusions, and a few in alveolar epithelial cells and pulmonary interstitial tissue (with no microscale particles present). Notably, damage to alveolar epithelial cells, macrophages, vascular endothelial cells, and the blood-gas barrier was observed. Given the well-documented toxicity of microscale silica, it is possible that these silica nanoparticles may have contributed in part to the illness reported in these workers. Such a possibility supports the adoption of controls and prevention strategies to minimize inhalation of nanoparticles by workers, and it highlights the urgent need and the importance of the nanosafety study in humans.

Occupational exposure to silica and lung cancer: pooled analysis of two case-control studies in Montreal, Canada.

BACKGROUND: Respirable crystalline silica is a highly prevalent occupational exposure and a recognized lung carcinogen. Most previous studies have focused on selected high-exposure occupational groups. This study examines the relationship between occupational exposure to silica and lung cancer in an occupationally diverse male population. METHODS: Two large population-based case-control studies of lung cancer were conducted in Montreal, one in 1979-1986 (857 cases, 533 population controls, 1,349 cancer controls) and the second in 1996-2001 (738 cases and 899 controls). Interviews provided descriptive lifetime job histories, smoking histories, and other information. Industrial hygienists translated job histories into histories of exposure to a host of occupational substances, including silica. Relative risk was estimated, adjusting for several potential confounders, including smoking. RESULTS: The odds ratio for substantial exposure to silica was 1.67 (95% confidence interval, 1.21-2.31) and for any exposure was 1.31 (95% confidence interval, 1.08-1.59). Joint effects between silica and smoking were between additive and multiplicative, perhaps closer to the latter. In this population, it is estimated that approximately 3% of lung cancers were attributable to substantial silica exposure. CONCLUSIONS: The carcinogenicity of inhaled crystalline silica was observed in a population with a wide variety of exposure circumstances. IMPACT: The finding of carcinogenicity across a wide range of occupations complements prior studies of specific high-exposure occupations. This suggests that the burden of cancer induced by silica may be much greater than previously thought.

Autoantibodies in silicosis patients and in silica-exposed individuals.

The aim of this study was to evaluate the prevalence of autoantibodies in silica-exposed patients with and without silicosis and without any known rheumatic disease. We studied 61 males exposed to silica for a mean time of 12.2 +/- 10.2 years of exposure. A total of 72.1% (44/61) of them presented with pulmonary silicosis. As control group we included 62 healthy males. In all samples we screened for rheumatoid factor (latex agglutination), antinuclear antibodies (indirect immunofluorescence), anti Scl-70 (ELISA) and ANCA (indirect immunofluorescence technique). One patient (1.6%) of the silica group had weakly positive ANA (titer 1:80, centromeric pattern); one (1.6%) had atypical ANCA and seven patients (11.4%) presented positive rheumatoid factor (values range from 8 to 32 UI/ml). One control patient had a positive RF and none of them had positive ANA or ANCA. All patients and controls were negative for anti-Scl-70. The finding of positive RF was higher in the silica-exposed patients (p = 0.032; Fisher). All patients with positive RF had pulmonary silicosis. In the silica-exposed group we could not find a relationship between the presence of RF and age (p = 0.21; Mann-Whitney), smoking habits (p = 0.25; Fisher) but a positive relationship was found with exposure time to silica dust (p = 0.005; Mann-Whitney). We conclude that there was 11.4% prevalence of low titer RF in the silica-exposed patients without known rheumatic disease. RF was more common in patients with longer exposure to silica dust and appeared only in those with silicosis. The presence of ANA, Scl-70 and ANCA was the same as in the control population.

Engineering control technologies to reduce occupational silica exposures in masonry cutting and tuckpointing.

OBJECTIVES: A number of tasks in construction generate worker overexposures to respirable crystalline silica dust, which is a significant contributor to occupational mortality and morbidity. This study evaluated the performance of commercially available engineering controls used in dusty construction tasks commonly performed by bricklayers. METHODS: Local exhaust ventilation (LEV) controls for a portable abrasive cutter and for tuckpointing grinders were examined at a bricklayers' training center, as were two stationary wet saws. Personal breathing zone air samples were collected with and without the use of LEV or water suppression during simulated concrete block cutting, brick cutting, and tuckpointing. RESULTS: Compared with the use of no exposure control during block and brick cutting, the portable LEV unit significantly reduced mean respirable quartz exposures by 96% for block cutting and 91% for brick cutting (p < 0.01). The use of stationary wet saws was also associated with 91% reductions in exposure (p < 0.01). For tuckpointing, the reductions in mean respirable quartz concentrations were between 91% and 93% with the LEV controls (p < 0.05). CONCLUSIONS: Reductions of up to 96% in mean respirable quartz concentration were observed between control and no-control scenarios. These reductions with commercially available off-the-shelf tools demonstrate the effectiveness of engineering control interventions to reduce crystalline silica exposures in construction. Strategies to further improve control performance and approaches for increasing control interventions in construction are needed.

Mortality in the German porcelain industry 1985-2005: first results of an epidemiological cohort study.

OBJECTIVES: To evaluate mortality due to lung cancer, silicosis, renal cancer, renal disease and other causes among German porcelain production workers potentially exposed to crystalline silica. METHODS: Seventeen thousand six hundred forty-four medical surveillance participants (1985-1987) were followed through 2005 for mortality. Cause-specific Standardized Mortality Ratios (SMR) and 95% confidence intervals were estimated. RESULTS: Women (SMR = 0.85; 95% CI = 0.78 to 0.93), but not men, demonstrated a healthy worker effect. Lung and renal cancers, and renal disease (non-malignant renal disease) were not associated with employment or exposure surrogates. Mortality was increased from silicosis (SMR = 7.20; 95% CI = 2.32 to 16.8) liver (SMR = 1.99; 95% CI = 1.29 to 2.93) and pancreatic (SMR = 1.71; 95% CI = 1.18 to 2.41) cancers among men, and diabetes among women (SMR = 1.74; 95% CI = 1.07 to 2.65). A sub-cohort of Bavarian workers generated similar but generally higher SMRs. CONCLUSIONS: Silicosis mortality was increased in this, among the largest studies to date. However, associations previously observed between crystalline silica exposure and renal or lung cancers or non-malignant renal disease were not supported.

New developments in the understanding of immunology in silicosis.

PURPOSE OF REVIEW: There is compelling evidence that the immune responses induced by crystalline silica particles are implicated in the development of silicosis. This article reviews recent observations which further delineate how innate and adaptive immunity are involved in this lung disease. RECENT FINDINGS: First, silica particles are recognized to have pathogen-associated molecular patterns by the innate immune system. The MARCO receptor expressed on the surface of macrophages appears crucial for the recognition and the uptake of silica as well as the activation of these immune cells in silicosis. Additional data support a major role of inflammation (mast cells, B lymphocytes and TNFalpha) in the development of lung fibrosis but also cancer. Silica-induced acute inflammation is accompanied by thrombosis; strongly suggesting that inhaled silica particles may also induce extrapulmonary lesions. Surprisingly, a pronounced anti-inflammatory reaction may also contribute to silica-induced lung fibrosis in mice and represent an additional etiopathogenic pathway of silicosis. Interestingly, it has been proposed that the pulmonary expression of IL-9 (a T lymphocyte-related interleukin) or Heme oxygenase-1 (an anti-inflammatory molecule) attenuated silicotic disease progression in animals. SUMMARY: New pathogenic routes involving innate receptors and antiinflammation as well as new antifibrotic immune mediators have been recently described in experimental silicosis, highlighting new potential therapeutic targets and strategies.

Chronic obstructive pulmonary disease and occupational exposure to silica.

Prolonged exposure to high levels of silica has long been known to cause silicosis This paper evaluates the evidence for an increased risk of chronic obstructive pulmonary disease (COPD) in occupations and industries in which exposure to crystalline silica is the primary exposure, with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests consistently elevated risks of developing COPD associated with silica exposure in several occupations, including the construction industry; tunneling; cement industry; brick manufacturing; pottery and ceramic work; silica sand, granite and diatomaceous earth industries; gold mining; and iron and steel founding, with risk estimates being high in some, even after taking into account the effect of confounders like smoking. Average dust levels vary from about 0.5 mg.m3 to over 10 mg.m3 and average silica levels from 0.04 to over 5 mg.m3, often well above occupational standards. Factors influencing the variation from industry to industry in risks associated with exposure to silica-containing dusts include (a) the presence of other minerals in the dust, particularly when associated with clay minerals; (b) the size of the particles and percentage of quartz; (c) the physicochemical characteristics, such as whether the dust is freshly fractured. Longitudinal studies suggest that loss of lung function occurs with exposure to silica dust at concentrations of between 0.1 and 0.2 mg.m3, and that the effect of cumulative silica dust exposure on airflow obstruction is independent of silicosis. Nevertheless, a disabling loss of lung function in the absence of silicosis would not occur until between 30 and 40 years exposure.

Photooxidation of a mustard gas simulant over TiO2-SiO2 mixed-oxide photocatalyst: site poisoning by oxidation products and reactivation.

The photooxidation of 2-chloroethyl ethyl sulfide (2-CEES), a simulant for mustard gas, was studied using transmission IR spectroscopy on a mixed-oxide TiO2-SiO2 photocatalyst. Ultraviolet irradiation in the photon energy range from 2.1 to 5 eV was employed at a catalyst temperature of 200 K. Rapid photooxidation was observed by the loss of infrared intensity in the v(CHx) stretching region, and concomitant infrared features of adsorbed oxidation products were observed to develop. The oxidation products, captured on the photocatalyst at 200 K, were found to block 2-CEES readsorption. Upon heating the poisoned photocatalyst to about 300 K, infrared measurements indicate that the adsorbed CO2 oxidation product was desorbed. The capability for full readsorption of 2-CEES was achieved upon heating the poisoned photocatalyst to 397 K, and continued rapid photooxidation of the 2-CEES was then possible at about 1/3 the rate found for the fresh catalyst. Thus thermal treatment at 397 K of oxidation-product-poisoned TiO2-SiO2 material is able to partially restore the TiO2-SiO2 photooxidation activity.

Silica exposure and systemic vasculitis.

Work in Department of Energy (DOE) facilities has exposed workers to multiple toxic agents leading to acute and chronic diseases. Many exposures were common to numerous work sites. Exposure to crystalline silica was primarily restricted to a few facilities. I present the case of a 63-year-old male who worked in DOE facilities for 30 years as a weapons testing technician. In addition to silica, other workplace exposures included beryllium, various solvents and heavy metals, depleted uranium, and ionizing radiation. In 1989 a painful macular skin lesion was biopsied and diagnosed as leukocytoclastic vasculitis. By 1992 he developed gross hematuria and dyspnea. Blood laboratory results revealed a serum creatinine concentration of 2.1 mg/dL, ethrythrocyte sedimentation rate of 61 mm/hr, negative cANCA (antineutrophil cytoplasmic antibody cytoplasmic pattern), positive pANCA (ANCA perinuclear pattern), and antiglomerular basement membrane negative. Renal biopsy showed proliferative (crescentric) and necrotizing glomerulonephritis. The patient's diagnoses included microscopic polyangiitis, systemic necrotizing vasculitis, leukocytoclastic vasculitis, and glomerulonephritis. Environmental triggers are thought to play a role in the development of an idiopathic expression of systemic autoimmune disease. Crystalline silica exposure has been linked to rheumatoid arthritis, scleroderma, systemic lupus erythematosus, rapidly progressive glomerulonephritis and some of the small vessel vasculitides. DOE workers are currently able to apply for compensation under the federal Energy Employees Occupational Illness Compensation Program (EEOICP). However, the only diseases covered by EEOICP are cancers related to radiation exposure, chronic beryllium disease, and chronic silicosis.