Results from omic approaches in rat or mouse models exposed to inhaled crystalline silica: a systematic review.

BACKGROUND: Crystalline silica (cSiO2) is a mineral found in rocks; workers from the construction or denim industries are particularly exposed to cSiO2 through inhalation. cSiO2 inhalation increases the risk of silicosis and systemic autoimmune diseases. Inhaled cSiO2 microparticles can reach the alveoli where they induce inflammation, cell death, auto-immunity and fibrosis but the specific molecular pathways involved in these cSiO2 effects remain unclear. This systematic review aims to provide a comprehensive state of the art on omic approaches and exposure models used to study the effects of inhaled cSiO2 in mice and rats and to highlight key results from omic data in rodents also validated in human. METHODS: The protocol of systematic review follows PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Eligible articles were identified in PubMed, Embase and Web of Science. The search strategy included original articles published after 1990 and written in English which included mouse or rat models exposed to cSiO2 and utilized omic approaches to identify pathways modulated by cSiO2. Data were extracted and quality assessment was based on the SYRCLE's Risk of Bias tool for animal studies. RESULTS: Rats and male rodents were the more used models while female rodents and autoimmune prone models were less studied. Exposure of animals were both acute and chronic and the timing of outcome measurement through omics approaches were homogeneously distributed. Transcriptomic techniques were more commonly performed while proteomic, metabolomic and single-cell omic methods were less utilized. Immunity and inflammation were the main domains modified by cSiO2 exposure in lungs of mice and rats. Less than 20% of the results obtained in rodents were finally verified in humans. CONCLUSION: Omic technics offer new insights on the effects of cSiO2 exposure in mice and rats although the majority of data still need to be validated in humans. Autoimmune prone model should be better characterised and systemic effects of cSiO2 need to be further studied to better understand cSiO2-induced autoimmunity. Single-cell omics should be performed to inform on pathological processes induced by cSiO2 exposure.

Crystalline silica-induced pulmonary inflammation and autoimmunity in mature adult NZBW/f1 mice: age-related sensitivity and impact of omega-3 fatty acid intervention.

OBJECTIVE: Occupational exposure to respirable crystalline silica (cSiO2) has been linked to lupus development. Previous studies in young lupus-prone mice revealed that intranasal cSiO2 exposure triggered autoimmunity, preventable with docosahexaenoic acid (DHA). This study explores cSiO2 and DHA effects in mature lupus-prone adult mice, more representative of cSiO2-exposed worker age. METHODS: Female NZBWF1 mice (14-week old) were fed control (CON) or DHA-supplemented diets. After two weeks, mice were intranasally instilled saline (VEH) or 1 mg cSiO2 weekly for four weeks. Cohorts were then analyzed 1- and 5-weeks postinstillation for lung inflammation, cell counts, chemokines, histopathology, B- and T-cell infiltration, autoantibodies, and gene signatures, with results correlated to autoimmune glomerulonephritis onset. RESULTS: VEH/CON mice showed no pathology. cSiO2/CON mice displayed significant ectopic lymphoid tissue formation in lungs at 1 week, increasing by 5 weeks. cSiO2/CON lungs exhibited elevated cellularity, chemokines, CD3+ T-cells, CD45R + B-cells, IgG + plasma cells, gene expression, IgG autoantibodies, and glomerular hypertrophy. DHA supplementation mitigated all these effects. DISCUSSION: The mature adult NZBWF1 mouse used here represents a life-stage coincident with immunological tolerance breach and one that more appropriately represents the age (20-30 yr) of cSiO2-exposed workers. cSiO2-induced robust pulmonary inflammation, autoantibody responses, and glomerulonephritis in mature adult mice, surpassing effects observed previously in young adults. DHA at a human-equivalent dosage effectively countered cSiO2-induced inflammation/autoimmunity in mature mice, mirroring protective effects in young mice. CONCLUSION: These results highlight life-stage significance in this preclinical lupus model and underscore omega-3 fatty acids' therapeutic potential against toxicant-triggered autoimmune responses.

A study of inflammatory biomarkers in crystalline silica exposed rock drillers.

BACKGROUND: Crystalline silica (CS) exposure can cause serious lung disease in humans, but mechanisms of pulmonary toxicity have not been completely elucidated. AIMS: To assess pro-inflammatory and anti-inflammatory biomarkers and biomarkers related to the development of chronic obstructive pulmonary disease and fibrosis in serum of rock drillers exposed to CS. METHODS: Rock drillers (N = 123) exposed to CS and non-specified particulate matter (PM) were compared to 48 referents without current or past exposure to PM in a cross-sectional study. RESULTS: The rock drillers had been exposed to CS for 10.7 years on average. Geometric mean (GM) current exposure was estimated to 36 µg/m3. Their GM concentration of matrix metalloproteinase 12 (MMP-12) was significantly higher (16 vs. 13 ng/L; p = 0.04), while interleukin (IL) 6 and IL-8 were significantly lower compared to the referents. Also pentraxin 3 was significantly lower (3558 vs. 4592 ng/L; p = 0.01) in the rock drillers. A dose-response relationship was observed between cumulative exposure to CS and MMP-12, the highest exposed subgroup having significantly higher MMP-12 concentrations than the referents. CONCLUSION: Exposure to CS may increase circulating MMP-12 concentrations in a dose-response related fashion. The results may also suggest a down-regulation of pro-inflammatory pathways.

Accelerated silicosis in sandblasters: Pathology, mineralogy, and clinical correlates.

BACKGROUND: With increasing reports of accelerated and acute silicosis, PMF, and autoimmune disease among coal miners and silica-exposed countertop workers, we present previously incompletely-described pulmonary pathology of accelerated silicosis and correlations with mineralogy, radiography, and disease progression in 46 Texas oilfield pipe sandblasters who were biopsied between 1988 and 1995. METHODS: Worker examinations included pulmonary function tests, chest X-ray (CXR), high-resolution computed tomography (HRCT), and Gallium-67 scans. Quantitative mineralogic analysis of pulmonary parenchymal burden of silica, silicates, and metal particles used scanning electron microscopy with energy dispersive x-ray spectroscopy (SEM EDS). RESULTS: Workers had clinical deterioration after <10 years exposure in dusty workplaces. Although initial CXR was normal in 54%, Gallium-67 scans were positive in 68% of those with normal CXR, indicating pulmonary inflammation. The histology of accelerated silicosis is diffuse interstitial infiltration of macrophages filled with weakly birefringent particles with or without silicotic nodules or alveolar proteinosis. Lung silica concentrations were among the highest in our database, showing a dose-response relationship with CXR, HRCT, and pathologic changes (macrophages, fibrosis, and silicotic nodules). Radiographic scores and diffusing capacity worsened during observation. Silica exposure was intensified, patients presented younger, with shorter exposure, more severe clinical abnormalities, higher lung particle burdens, and more rapid progression in a subset of patients exposed to recycled blasting sand. CONCLUSIONS: Accelerated silicosis may present with a normal CXR despite significant histopathology. Multivariable analyses showed silica, and not other particles, is the driver of observed radiologic, physiologic, and histologic outcomes. Eliminating this preventable disease requires higher physician, public health, and societal awareness.

Paracrine signaling of ferroptotic airway epithelium in crystalline silica-induced pulmonary fibrosis augments local fibroblast activation through glycolysis reprogramming.

Chronic exposure to crystalline silica (CS) contributes to pulmonary fibrosis. Airway epithelium dysfunction and fibroblast activation have both been recognized as pivotal players, alongside disturbances in ferroptosis and glycolysis reprogramming. However, the mechanisms involved remain unclear. In this study, we investigated the crosstalk between airway epithelium and fibroblast in the context of CS-induced pulmonary fibrosis. CS was employed in vivo and the in vitro co-culture system of airway epithelium and fibroblast. Spatial transcriptome analysis of CS-induced fibrotic lung tissue was conducted as well. Results showed that epithelium ferroptosis caused by CS enhanced TGFß1-induced fibroblast activation through paracrine signaling. tPA was further identified to be the central mediator that bridges epithelium ferroptosis and fibroblast activation. And increased fibroblast glycolysis reprogramming was evidenced to promote fibroblast activation. By inhibition of epithelium ferroptosis or silencing tPA of airway epithelium, fibroblast AMPK phosphorylation was inhibited. Moreover, we revealed that tPA secreted by ferroptotic epithelium transmits paracrine signals to fibroblasts by governing glycolysis via p-AMPK/AMPK mediated Glut1 accumulation. Collectively, our study demonstrated the regulation of airway epithelium ferroptosis on fibroblast activation in CS-induced pulmonary fibrosis, which would shed light on the complex cellular crosstalk within pulmonary fibrosis and identify potential therapeutic targets.

A Portable Infrared System for Identification of Particulate Matter.

Occupational exposure to airborne dust is responsible for numerous respiratory and cardiovascular diseases. Because of these hazards, air samples are regularly collected on filters and sent for laboratory analysis to ensure compliance with regulations. Unfortunately, this approach often takes weeks to provide a result, which makes it impossible to identify dust sources or protect workers in real time. To address these challenges, we developed a system that characterizes airborne dust by its spectro-chemical profile. In this device, a micro-cyclone concentrates particles from the air and introduces them into a hollow waveguide where an infrared signature is obtained. An algorithm is then used to quantitate the composition of respirable particles by incorporating the infrared features of the most relevant chemical groups and compensating for Mie scattering. With this approach, the system can successfully differentiate mixtures of inorganic materials associated with construction sites in near-real time. The use of a free-space optic assembly improves the light throughput significantly, which enables detection limits of approximately 10 µg/m3 with a 10 minute sampling time. While respirable crystalline silica was the focus of this work, it is hoped that the flexibility of the platform will enable different aerosols to be detected in other occupational settings.

Evaluation of PVC and PTFE filters for direct-on-filter crystalline silica quantification by FTIR.

Direct-on-Filter (DoF) analysis of respirable crystalline silica (RCS) by Fourier Transform Infrared (FTIR) spectroscopy is a useful tool for assessing exposure risks. With the RCS exposure limits becoming lower, it is important to characterize and reduce measurement uncertainties. This study systematically evaluated two filter types (i.e., polyvinyl chloride [PVC] and polytetrafluoroethylene [PTFE]) for RCS measurements by DoF FTIR spectroscopy, including the filter-to-filter and day-to-day variability of blank filter FTIR reference spectra, particle deposition patterns, filtration efficiencies, and pressure drops. For PVC filters sampled at a flow rate of 2.5 L/min for 8 h, the RCS limit of detection (LOD) was 7.4 µg/m3 when a designated laboratory reference filter was used to correct the absorption by the filter media. When the spectrum of the pre-sample filter (blank filter before dust sampling) was used for correction, the LOD could be up to 5.9 µg/m3. The PVC absorption increased linearly with reference filter mass, providing a means to correct the absorption differences between the pre-sample and reference filters. For PTFE, the LODs were 12 and 1.2 µg/m3 when a designated laboratory blank or the pre-sample filter spectrum was used for blank correction, respectively, indicating that using the pre-sample blank spectrum will reduce RCS quantification uncertainty. Both filter types exhibited a consistent radially symmetric deposition pattern when particles were collected using 3-piece cassettes, indicating that RCS can be quantified from a single measurement at the filter center. The most penetrating aerodynamic diameters were around 0.1 µm with filtration efficiencies ≥ 98.8% across the measured particle size range with low-pressure drops (0.2-0.3 kPa) at a flow rate of 2.5 L/min. This study concludes that either the PVC or the PTFE filters are suitable for RCS analysis by DoF FTIR, but proper methods are needed to account for the variability of blank absorption among different filters.

Crystalline silica exposure in patients with rheumatoid arthritis and systemic sclerosis: a nationwide cross-sectional survey.

OBJECTIVES: Develop and validate a thorough exposure questionnaire to comprehensively explore crystalline silica (SiO2) exposure in the general population (gender-specific, occupational and non-occupational) and in patients with autoimmune diseases (rheumatoid arthritis (RA), systemic sclerosis (SSc)). METHODS: Lifetime exposures to SiO2 in occupational and non-occupational settings were assessed using a thorough exposure questionnaire. The questionnaire was applied to a general population panel (n = 2911) sampled from the French rolling census, and to unselected patients with SSc (n = 100) and RA (n = 97). Global (GES), occupational (OES) and non-occupational (NOES) exposure scores were assessed in SSc and RA patients, and compared with up to four controls from the general population, matched by age group, sex and tobacco consumption. RESULTS: Patients had higher GES than their matched controls (SSc: P = 0.001; RA: P < 0.0001) due to higher OES (P < 0.0001 for SSc and RA). Men had higher GES than women (SSc: P < 0.0001; RA: P = 0.002) due to higher OES (P < 0.0001 for SSc and RA). The NOES did not differ between men and women. In SSc patients: Men had higher GES than controls (P < 0.0001). Men and women with SSc had higher OES than controls (P < 0.0001). In RA patients: GES and OES were higher in both men (P = 0.00521; P < 0.0001) and women (P < 0.0001; P < 0.0001) than in their respective controls. Women had higher NOES than controls (P = 0.045). CONCLUSION: The lifetime SiO2 exposure gap between RA and SSc patients and controls was substantially due to occupational exposure. In both diseases, men had higher exposure scores than women.

Occupational quantitative exposure to crystalline silica, solvents, pesticides, and risk of clinical forms of systemic sclerosis.

OBJECTIVES: To estimate the association between SSc clinical phenotypes and quantitative occupational exposure to crystalline silica, chlorinated solvents, trichloroethylene, and pesticides using job-exposure matrices. METHODS: In the VISS-EXPOSITION transversal study, data on declarative occupational exposure to crystalline silica, solvents, and pesticides were retrieved. In parallel, the Lifetime Occupational History was evaluated using a questionnaire and cursus laboris for SSc patients followed at Bordeaux University Hospital (France). Using job-exposure matrices, we assessed patients' occupational exposure in relation to relevant clinical phenotypic forms of the disease. RESULTS: Toxic exposure to crystalline silica and pesticides is underestimated by patients. Non-biased job-exposure matrices retrieved more exposed patients than the declarative assessment (10.1% of patients by job-exposure matrices versus 6.3% by declaration for crystalline silica and 25.9% versus 12.2% for pesticides). Patients overestimate their solvent exposure (7.9% for chlorinated solvents and 4.8% for trichlorethylene assessed by job-exposure matrices and 24.4% declarative exposure to solvents at large). Clinical form evaluation revealed a nonsignificant trend toward an increased risk of crystalline silica occupational exposure in the pulmonary fibrotic group of SSc patients (OR 3.12 CI 95% [0.80-12.15]). We also observed a nonsignificant trend toward elevated OR (OR 2.89 CI 95% [0.93-8.95]) for chlorinated solvent occupational exposure and the vascular phenotype of SSc. Of note, pesticide occupational exposure evaluation represents one of the largest to date in SSc patients. CONCLUSION: This study emphasizes that many exposed SSc patients are unaware of their occupational exposure. Job-exposure matrices allow better exposure screening for SSc secondary prevention and occupational exposure compensation. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03543956.

Crystalline Silica-Induced Proinflammatory Interstitial Macrophage Recruitment through Notch3 Signaling Promotes the Pathogenesis of Silicosis.

Crystalline silica (CS) particles are ubiquitous in the environment, especially in occupational conditions, and exposure to respirable CS causes silicosis. The initial response to CS is mediated by innate immunity, where pulmonary macrophages act as central orchestrators. However, the repercussions of CS on functionally distinct macrophage subsets remain to be inconclusive. Herein, to study the effects of inhaled CS, we divided macrophages into three subsets: circulating monocytes, interstitial macrophages (IMs), and alveolar macrophages (AMs). CS-induced massive IMs increase in the lung, the phenotype and function of which differed from those of tissue-resident AMs and circulating monocytes. The augmented IMs were driven by recruitment of circulating macrophages rather than cell proliferation in situ. Moreover, the IMs predominantly exerted a classic activated (M1) phenotype and expressed proinflammatory cytokines, contributing to CS-induced lung injury. Notably, we demonstrated that IMs augmented Notch3 expression. Mechanistically, using myeloid-specific Notch3-knockout mice, we demonstrated that Notch3 signaling not only promoted IMs recruitment by regulating CCR2 expression but also manipulated the proinflammatory phenotype. Mice with conditional Notch3-knockout exhibited alleviation of CS-induced inflammation and fibrosis in lung. Overall, our study identifies IMs as critical mediators in response to CS and highlights the role of Notch3 in IMs recruitment and activation, providing new insights into CS toxicological effects in the lung.

The impact of occupational exposure to crystalline silica dust on respiratory function (airway obstruction and FEF25-75) in the French general population.

INTRODUCTION: Although several studies have studied the relationship between occupational exposure to crystalline silica dust and respiratory mortality, few have examined the relationship with impairments in respiratory function and the exposure threshold triggering spirometric monitoring in exposed workers. The objective of the present study was to evaluate the impact of exposure to crystalline silica dust on respiratory function. METHODS: We included 1428 male participants (aged 40 to 65) recruited from the French general population, at random from electoral rolls, in the cross-sectional ELISABET study and for whom data on forced expiratory flow-volume curve indices z-scores (calculated using the Global Lung Function Initiative 2012 equations) and exposure (via a questionnaire) were available. A cumulative exposure index (CEI) for crystalline silica dust (CEIsilica, expressed in mg.m-3.year) was calculated using the Matgéné occupational exposure matrix. RESULTS: 293 of the 1428 participants (20.52%) reported exposure to silica dust. We found that the adjusted z-scores for the forced expiratory volume in the first second/forced vital capacity (FEV1/FVC) ratio decreased significantly as CEIsilica increased. After adjustment, the adjusted z-scores for FEV1/FVC (ß: -0.426 (95% confidence interval (CI): -0.792, -0.060) per 1 mg m-3.year increment) and the mean forced expiratory flow between 25 and 75% of the forced vital capacity (FEF25-75) (ß: -0.552 (95% CI: -0.947, -0.157)) were significantly lower in the participants with CEIsilica ≥1 mg m-3.year than in non-exposed participants. The likelihoods of having airway obstruction (odds ratio (OR): 3.056 (95% CI: 1.107, 7.626)) or having an impaired FEF25-75 (OR: 4.305 (95% CI: 1.393, 11.79)) were also significantly higher in participants with CEIsilica ≥1 mg m-3.year. CONCLUSION: Our results emphasize the importance of spirometry-based monitoring in workers exposed to more than 1 mg m-3.year of crystalline silica dust, in order to identify small airway obstruction or airway obstruction as early as possible.

Occupational exposure to respirable crystalline silica and lung cancer: a systematic review of cut-off points.

BACKGROUND: Respirable crystalline silica (RCS) is associated with the development of lung cancer. However, there is uncertainty around the exposure threshold at which exposure to RCS may pose a clear risk for the development of lung cancer. The objective of this study was to review the cut-off points at which the risk of mortality or incidence of lung cancer due to occupational exposure to RCS becomes evident through a systematic review. METHODS: We conducted a search in PubMed, including cohort and case-control studies which assessed various categories of RCS exposure. A search was also conducted on the webpages of institutional organizations. A qualitative data synthesis was performed. RESULTS: Twenty studies were included. Studies that assessed lung cancer mortality and incidence displayed wide variability both in RCS exposure categories and related risks. Although most studies found no significant association for RCS exposure categories, it appears to be a low risk of lung cancer for mean concentrations of less than 0.07mg/m3. Regulatory agencies set annual RCS exposure limits ranging from 0.025mg/m3 through 0.1mg/m3. CONCLUSIONS: There is a wide degree of heterogeneity in RCS exposure categories, with most studies observing no significant risk of lung cancer for the lowest exposure categories. Cut-off points differ between agencies but are nonetheless very similar and do not exceed 0.1mg/m3.

Time-course analysis of pulmonary inflammation induced by intratracheal instillation of nanosized crystalline silica particles in F344 rats.

Crystalline silica is an important cause of serious pulmonary diseases, and its toxic potential is known to be associated with its surface electrical properties. However, in vivo data clarifying the relevance of silica's toxic potential, especially its long-term effects, remain insufficient. To investigate the contribution of physico-chemical property including surface potential on the hazard of nanocrystalline silica, we performed single intratracheal instillation testing using five different crystalline silicas in a rat model and assessed time-course changes in pulmonary inflammation, lung burden, and thoracic lymph node loads. Silica-nanoparticles were prepared from two commercial products (Min-U-Sil5 [MS5] and SIO07PB [SPB]) using three different pretreatments: centrifugation (C), grinding (G), and surface dissolving (D). The five types of silica particles-MS5, MS5_C, SPB_C, SPB_G, and SPB_D-were intratracheally instilled into male F344 rats at doses of 0 mg/kg (purified water), 0.22 mg/kg (SPB), and 0.67, 2, or 6 mg/kg (MS5). Bronchoalveolar lavage, a lung burden analysis, and histopathological examination were performed at 3, 28, and 91 days after instillation. Granuloma formation was present in MS5 group at 91 days after instillation, although granuloma formation was suppressed in MS5_C group, which had a smaller particle size. SPB_C induced severe and progressive inflammation and kinetic lung overload, whereas SPB_G and SPB_D induced only slight and transient acute inflammation. Our results support that in vivo toxic potential of nanosilica by intratracheal instillation may involve with surface electrical properties leading to prolonged effect and may not be dependent not only on surface properties but also on other physico-chemical properties.

Silicosis, asbestosis, and pulmonary fibrosis in Ontario, Canada from 1996 to 2019.

BACKGROUND: Silicosis is a fibrotic lung disease caused by exposure to respirable crystalline silica. Historically, silicosis was common among miners and other professions in the 20th century, and in recent decades has re-emerged in coal mining and appeared in new workplaces, including the manufacture of distressed jeans and artificial stone countertops. METHODS: Physician billing data for the province of Ontario between 1992 and 2019 were analyzed across six time-periods (1993-1995, 1996-2000, 2001-2005, 2006-2010, 2011-2015, and 2016-2019). The case definition was two or more billing records within 24 months with a silicosis diagnosis code (ICD-9 502, ICD-10 J62). Cases from 1993 to 1995 were excluded as prevalent cases. Crude incidence rates per 100,000 persons were calculated by time-period, age, sex, and region. Analyses were repeated in parallel for pulmonary fibrosis (PF) (ICD-9 515, ICD-10 J84) and asbestosis (ICD-9 501; ICD-10 J61). RESULTS: From 1996 to 2019, 444 cases of silicosis, 2719 cases of asbestosis and 59,228 cases of PF were identified. Silicosis rates decreased from 0.42 cases per 100,000 in 1996-2000 to 0.06 per 100,000 people in 2016-2019. A similar trend was observed for asbestosis (1.66 to 0.51 per 100,000 persons) but the incidence rate of PF increased from 11.6 to 33.9 per 100,000 persons. Incidence rates for all outcomes were higher among men and older adults. CONCLUSIONS: A decreasing incidence of silicosis was observed in this analysis. However, the incidence of PF increased, consistent with findings from other jurisdictions. While cases of silicosis have been recorded among artificial stone workers in Ontario these cases do not seem to have impacted the population rates thus far. Ongoing, periodic surveillance of occupational diseases is helpful for tracking population-level trends over time.

Identification of a Gene Signature Predicting (Nano)Particle-Induced Adverse Lung Outcome in Rats.

Nanoparticles are extensively used in industrial products or as food additives. However, despite their contribution to improving our quality of life, concerns have been raised regarding their potential impact on occupational and public health. To speed up research assessing nanoparticle-related hazards, this study was undertaken to identify early markers of harmful effects on the lungs. Female Sprague Dawley rats were either exposed to crystalline silica DQ-12 with instillation, or to titanium dioxide P25, carbon black Printex-90, or multi-walled carbon nanotube Mitsui-7 with nose-only inhalation. Tissues were collected at three post-exposure time points to assess short- and long-term effects. All particles induced lung inflammation. Histopathological and biochemical analyses revealed phospholipid accumulation, lipoproteinosis, and interstitial thickening with collagen deposition after exposure to DQ-12. Exposure to the highest dose of Printex-90 and Mitsui-7, but not P25, induced some phospholipid accumulation. Comparable histopathological changes were observed following exposure to P25, Printex-90, and Mitsui-7. Comparison of overall gene expression profiles identified 15 potential early markers of adverse lung outcomes induced by spherical particles. With Mitsui-7, a distinct gene expression signature was observed, suggesting that carbon nanotubes trigger different toxicity mechanisms to spherical particles.

[The incidence of artificial stone-related silicosis among interior decoration workers in different countries].

In this paper, 177 cases of artificial stone-related silicosis in interior decoration workers from Israel, Spain, USA, Italy and Australia were analyzed. Interior decoration workers were from small businesses (or workshops), engaged in kitchen and/or bathroom artificial stone countertops cutting, grinding, polishing and other reprocessing. In the working environment, the content of crystalline silica in artificial stone was more than 70%, and the concentration of silica dust exceeded the relevant standards. Most workplaces used dry cutting without ventilation and dust removal and other dust-proof measures, and most workers did not wear qualified respiratory protective equipment. Taking comprehensive measures such as wet operation, ventilation and dust removal, and individual protection can effectively prevent the occurrence of artificial stone-related silicosis.

Crystalline silica induces macrophage necrosis and causes subsequent acute pulmonary neutrophilic inflammation.

Crystalline silica (CS), an airborne particulate, is a major global occupational health hazard. While it is known as an important pathogenic factor in many severe lung diseases, the underlying mechanisms of its toxicity are still unclear. In the present study, we found that intra-tracheal instillation of CS caused rapid emergence of necrotic alveolar macrophages. Cell necrosis was a consequence of the release of cathepsin B in CS-treated macrophages, which caused dysfunction of the mitochondrial membrane. Damage to mitochondria disrupted Na+/K+ ATPase activity in macrophages, leading to intracellular sodium overload and the subsequent cell necrosis. Further studies indicate that CS-induced macrophage necrosis and the subsequent release of mitochondrial DNA could trigger the recruitment of neutrophils in the lung, which was regulated by the TLR9 signaling pathway. In conclusion, our results suggest a novel mechanism whereby CS leads to rapid macrophage necrosis through cathepsin B release, following the leakage of mitochondrial DNA as a key event in the induction of pulmonary neutrophilic inflammation. This study has important implications for the early prevention and treatment of diseases induced by CS.

A study of pneumoproteins in crystalline silica exposed rock drillers.

Objective: The objective was to assess serum concentrations of club cell protein 16 (CC-16) and the surfactant proteins A (SPs-A) and D (SP-D) in male rock drillers (N = 123) exposed to crystalline silica and in 48 occupationally non-exposed. Methods: The arithmetic mean (AM) duration of exposure was 10.7 years. The geometric mean (GM) crystalline silica exposure was 36 µg/m3 at the time of the study. The GM cumulative exposure was 239 µg/m3. Results: The concentrations of SP-D (GM 12.7 vs. 8.8 µg/L, p < 0.001) and SP-A (AM 1847 vs. 1378 ng/L, p = 0.051) were higher among rock drillers than among occupationally non-exposed. A positive significant association was observed between cumulative crystalline silica exposure and the SP-D concentrations (ß = 0.07; p < 0.05). Rock drillers with small airway obstruction with maximal mid-expiratory flow % (MMEF%) <70% (N = 29) had higher SP-D concentrations than rock drillers with MMEF% ≥ 70% (N = 91) (GM 17.3 vs. 11.4 µg/L, p = 0.001). Rock drillers with MMEF% ≥70% (N = 91) had higher concentrations of SP-A (1957 vs. 1287 ng/L, p = 0.01) and SP-D (11.4 vs. 9.0 µg/L, p = 0.007) than non-exposed with MMEF% ≥70% (N = 39). Rock drillers with airway obstruction (FEV1/FVC < 0.70, N = 11) had significantly lower CC-16 concentrations than rock drillers with FEV1/FVC ≥0.70 (N = 109) after adjusting for relevant potential confounders (p = 0.02). Conclusion: The results indicate that pulmonary surfactant is a target for crystalline silica toxicity. The alterations appear to be driven by pulmonary alterations in the small airways and by exposure itself. Further studies on pneumoproteins and pulmonary function in other groups of workers exposed to crystalline silica are needed.

Elevated exposures to respirable crystalline silica among engineered stone fabrication workers in California, January 2019-February 2020.

BACKGROUND: Workers fabricating engineered stone face high risk for exposure to respirable crystalline silica (RCS) and subsequent development of silicosis. In response, the California Division of Occupational Safety and Health (Cal/OSHA) performed targeted enforcement inspections at engineered stone fabrication worksites. We investigated RCS exposures and employer adherence to Cal/OSHA's RCS and respiratory protection standards from these inspections to assess ongoing risk to stone fabrication workers. METHODS: We extracted employee personal air sampling results from Cal/OSHA inspection files and calculated RCS exposures. Standards require that employers continue monitoring employee RCS exposures and perform medical surveillance when exposures are at or above the action level (AL; 25 µg/m3 ); exposures above the permissible exposure limit (PEL; 50 µg/m3 ) are prohibited. We obtained RCS and respiratory protection standard violation citations from a federal database. RESULTS: We analyzed RCS exposures for 152 employees at 47 workplaces. Thirty-eight (25%) employees had exposures above the PEL (median = 89.7 µg/m3 ; range = 50.7-670.7 µg/m3 ); 17 (11%) had exposures between the AL and PEL. Twenty-four (51%) workplaces had ≥1 exposure above the PEL; 7 (15%) had ≥1 exposure between the AL and PEL. Thirty-four (72%) workplaces were cited for ≥1 RCS standard violation. Twenty-seven (57%) workplaces were cited for ≥1 respiratory protection standard violation. CONCLUSIONS: Our investigation demonstrates widespread RCS overexposure among workers and numerous employer Cal/OSHA standard violation citations. More enforcement and educational efforts could improve employer compliance with Cal/OSHA standards and inform employers and employees of the risks for RCS exposure and strategies for reducing exposure.

Sarcoidosis in Northern Ontario hard-rock miners: A case series.

Sarcoidosis is a rare multisystem granulomatous disease traditionally considered to be of unknown etiology. The notion that sarcoidosis has no known cause is called into question with the increasing number of case reports and epidemiologic studies showing associations between occupational exposures and disease published in the past 10-20 years. Occupational exposures for which associations are strongest and most consistent are silica and other inorganic dusts, World Trade Center (WTC) dust, and metals. Occupations identified as at-risk for sarcoidosis include construction workers; iron-foundry and diatomaceous earth workers; WTC emergency responders; and metal workers. We report here 12 cases of sarcoidosis in a cohort of hard-rock miners in Northern Ontario, Canada. To our knowledge sarcoidosis has not been reported previously in hard-rock miners. The cases are all male and Caucasian, with average age 74 years. At the time of diagnosis, two were never smokers; six, former smokers; and four, current smokers. Five have extrapulmonary sarcoidosis: two cardiac and three endocrine (hypercalciuria). Using occupational histories and air sampling data from the gold, uranium, and base-metal mines in which they worked, we examined exposure of each case to respirable crystalline silica (RCS). The annual mean RCS exposure for the 12 cases was 0.14 mg/m3 (range: 0.06-1.3 mg/m3 ); and the mean cumulative RCS exposure was 1.93 mg/m3  years (range: 0.64-4.03 mg/m3  years). We also considered their exposure to McIntyre Powder, an aluminum powder used for silicosis prophylaxis.