Quartz Dust Exposure Affects NLRP3 Inflammasome Activation and Plasma Levels of IL-18 and IL-1Ra in Iron Foundry Workers.
ABSTRACT: To study the association between inhalation of particulate matter or quartz in Swedish iron foundries and the effects on NLRP3 inflammasome activation. Particle exposure measurements were performed during an eight-hour work day for 85 foundry workers at three Swedish iron foundries. Personal sampling was used for measurement of respirable quartz and dust and stationary measurements to obtain exposure measurements for inhalable dust and PM10. The NLRP3 inflammasome markers, interleukin- (IL-) 1? and IL-18, and inhibitors IL-1 receptor antagonist (IL-1Ra) and IL-18 binding protein (IL-18BP) were measured in plasma. Inflammasome activation was measured by caspase-1 enzymatic activity in monocytes in whole blood by flow cytometry, and expression of inflammasome-related genes was quantified using real-time PCR. Multiple linear regression analysis was used to investigate associations between PM exposures and inflammatory markers. Sex, age, smoking, current infection, BMI, and single nucleotide polymorphism in the inflammasome regulating genes CARD8 (C10X) and NLRP3 (Q705K) were included as covariates. The average exposure levels of respirable dust and quartz were 0.85 and 0.052?mg/m3, respectively. A significant exposure-response was found for respirable dust and IL-18 and for inhalable dust and IL-1Ra. Whole blood, drawn from study participants, was stimulated ex vivo with inflammasome priming stimuli LPS or Pam3CSK4, resulting in a 47% and 49% increase in caspase-1 enzymatic activity in monocytes. This increase in caspase-1 activity was significantly attenuated in the higher exposure groups for most PM exposure measures. The results indicate that exposure levels of PM in the iron foundry environment can affect the NLRP3 inflammasome and systemic inflammation.
Project description:PURPOSE:To study the relationship between respirable dust, quartz and chemical binders in Swedish iron foundries and respiratory symptoms, lung function (as forced expiratory volume FEV1 and vital capacity FVC), fraction of exhaled nitric oxide (FENO) and levels of club cell secretory protein 16 (CC16) and CRP. METHODS:Personal sampling of respirable dust and quartz was performed for 85 subjects in three Swedish iron foundries. Full shift sampling and examination were performed on the second or third day of a working week after a work free weekend, with additional sampling on the fourth or fifth day. Logistic, linear and mixed model analyses were performed including, gender, age, smoking, infections, sampling day, body mass index (BMI) and chemical binders as covariates. RESULTS:The adjusted average respirable quartz and dust concentrations were 0.038 and 0.66 mg/m3, respectively. Statistically significant increases in levels of CC16 were associated with exposure to chemical binders (p = 0.05; p = 0.01) in the regression analysis of quartz and respirable dust, respectively. Non-significant exposure-responses were identified for cumulative quartz and the symptoms asthma and breathlessness. For cumulative chemical years, non-significant exposure-response were observed for all but two symptoms. FENO also exhibited a non significant exposure-response for both quartz and respirable dust. No exposure-response was determined for FEV1 or FVC, CRP and respirable dust and quartz. CONCLUSIONS:Our findings suggest that early markers of pulmonary effect, such as increased levels of CC16 and FENO, are more strongly associated with chemical binder exposure than respirable quartz and dust in foundry environments.
Project description:<i>Background:</i> Respirable crystalline silica (RCS) has been recognized as a human carcinogen; however, the measurement and analysis of RCS in small-scale foundries is rare and difficult. This study aimed to measure respirable dust and RCS levels among 236 foundry workers in Taiwan and used these data to establish predictive models for personal exposure. <i>Methods:</i> Personal sampling of various production processes were measured gravimetrically and analyzed using the X-ray diffraction method. Multiple linear regression was used to establish predictive models. <i>Results:</i> Foundry workers were exposed to geometric means and geometric standard deviations of 0.52 ± 4.0 mg/m³ and 0.027 ± 15 mg/m³ for respirable dust and RCS, respectively. The highest exposure levels were observed among workers in the sand blasting process, with geometric means of 1.6 mg/m³ and 0.099 mg/m³ for respirable dust and RCS, respectively. The predictive exposure model for respirable dust fitted the data well (R² = 0.75; adjusted R² = 0.64), and the predictive capacity for RCS was higher (R² = 0.89; adjusted R² = 0.84). <i>Conclusions:</i> Foundry workers in the sand blasting process may be exposed to the highest levels of respirable dust and RCS. The developed models can be applied to predict respirable dust and RCS levels adequately in small-scale foundry workers for epidemiological studies.
Project description:Indium-tin oxide production has increased greatly in the last 20 years subsequent to increased global demand for touch screens and photovoltaics. Previous studies used measurements of indium in blood as an indicator of indium exposure and observed associations with adverse respiratory outcomes. However, correlations between measurements of blood indium and airborne respirable indium are inconsistent, in part because of the long half-life of indium in blood, but also because respirable indium measurements do not incorporate inhalable indium that can contribute to the observed biological burden. Information is lacking on relationships between respirable and inhalable indium exposure, which have implications for biological indicators like blood indium. The dual IOM sampler includes the foam disc insert and can simultaneously collect respirable and inhalable aerosol. Here, the field performance of the dual IOM sampler was evaluated by comparing performance with the respirable cyclone and traditional IOM for respirable and inhalable indium and dust exposure, respectively. Side-by-side area air samples were collected throughout an indium-tin oxide manufacturing facility. Cascade impactors were used to determine particle size distribution. Several statistical methods were used to evaluate the agreement between the pairs of samplers including calculating the concordance correlation coefficient and its accuracy and precision components. One-way ANOVA was used to evaluate the effect of dust concentration on sampler differences. Respirable indium measurements showed better agreement (concordance correlation coefficient: 0.932) compared to respirable dust measurements (concordance correlation coefficient: 0.777) with significant differences observed in respirable dust measurements. The dual IOM measurements had high agreement with the traditional IOM for inhalable indium (concordance correlation coefficient: 0.997) but lower agreement for inhalable dust (concordance correlation coefficient: 0.886 and accuracy: 0.896) with a significantly large mean bias (-146.9 µg/m3). Dust concentration significantly affected sampler measurements of inhalable dust and inhalable indium. Results from this study suggest that the dual IOM is a useful single sampler for simultaneous measurements of occupational exposure to respirable and inhalable indium.
Project description:The South African mining industry is one of the largest producers of platinum (Pt) in the world. Workers in this industry are exposed to significant amounts of dust, and this dust consists of particles sizes that can penetrate deep inside the respiratory region. A cross-sectional study was conducted to evaluate dust exposure risk at two Pt mine waste rock crusher plants (Facility A and B) in Limpopo, South Africa. Workers' demographic and occupational information was collected through a structured questionnaire, a walk-through observation on facilities' processes, and static dust sampling for the collection of inhalable and respirable dust particles using the National Institute for Occupational Safety and Health (NIOH) 7602 and the Methods for Determination of Hazardous Substance (MDHS) 14/4 as guidelines. Only 79% of Pt mine workers, used their respiratory protective equipment (RPE), sixty-five percent were exposed to work shifts exceeding the recommended eight hours and 8.8% had been employed for more than ten years. The mean time-weighted average (TWA) dust concentrations between Facility A and B showed a significant difference (p < 0.026). The Pt mine's inhalable concentrations (range 0.03-2.2 mg/m3) were higher than the respirable concentrations (range 0.02-0.7 mg/m3), however were all below the respective international and local occupational exposure limits (OELs). The Pt mine's respirable crystalline silica (SiO2) quartz levels were all found below the detectable limit (<0.01 mg/m3). The Pt miners had increased health risks due to accumulated low levels of dust exposure and lack of usage of RPE. It is recommended that an improved dust control program be put in place which includes, but is not limited to, stockpile enclosures, tire stops with water sprays, and education on the importance of RPE) usage.
Project description:Exposure to occupational aerosols are a known hazard in many industry sectors and can be a risk factor for several respiratory diseases. In this study, a laboratory evaluation of low-cost aerosol sensors, the Dylos DC1700 and a modified Dylos known as the Utah Modified Dylos Sensor (UMDS), was performed to assess the sensors' efficiency in sampling respirable and inhalable dust at high concentrations, which are most common in occupational settings. Dust concentrations were measured in a low-speed wind tunnel with 3 UMDSs, collocated with an aerosol spectrometer (Grimm 1.109) and gravimetric respirable and inhalable samplers. A total of 10 tests consisting of 5 different concentrations and 2 test aerosols, Arizona road dust and aluminum oxide, were conducted. For the Arizona road dust, total particle count was strongly related between the spectrometer and the UMDS with a coefficient of determination (R2) between 0.86-0.92. Particle count concentrations measured with the UMDS were converted to mass and also were related with gravimetrically collected inhalable and respirable dust. The UMDS small bin (i.e., all particles) compared to the inhalable sampler yielded an R2 of 0.86-0.92, and the large bin subtracted from the small bin (i.e., only the smallest particles) compared to the respirable sampler yielded an R2 of 0.93-0.997. Tests with the aluminum oxide demonstrated a substantially lower relationship across all comparisons. Furthermore, assessment of intra-instrument variability was consistent for all instruments, but inter-instrument variability indicated that each instrument requires its own calibration equation to yield accurate exposure estimates. Overall, it appears that the UMDS can be used as a low-cost tool to estimate respirable and inhalable concentrations found in many workplaces. Future studies will focus on deployment of a UMDS network in an occupational setting.
Project description:<h4>Background</h4>Mild equine asthma is presumed to arise in response to environmental exposures but the relative impact of differing inflammatory phenotypes upon performance are largely unexplored.<h4>Hypotheses</h4>Airway inflammation negatively affects performance and cytological phenotype varies with environmental exposure.<h4>Animals</h4>Thoroughbred racehorses in active training and racing.<h4>Methods</h4>Thoroughbreds were recruited 24-48 hours before racing. Each horse was eligible for re-enrollment with each race entry. Within one hour of race completion, physical examination, respiratory endoscopy, and BAL were performed. Respirable and inhalable dust, respirable endotoxin, and respirable ?-glucan exposures were measured at the breathing zone within one week after racing. Controlling for age, trainer, and pulmonary hemorrhage, the relationship between performance, bronchoalveolar lavage fluid (BALF) cytology, and measures of exposure were modeled.<h4>Results</h4>Performance and BALF data were collected on 64 individual horses from 8 stables for a total of 98 race performances and 79 dust exposure assessments. Evidence of mild equine asthma was found in 80% (78/98) of BALF samples from 52/64 horses. For each percent increase in BALF mast cell and neutrophil proportions, speed figures were reduced by 2.9 (P?=?.012) and 1.4 (P?=?.046) points, respectively. Respirable dust concentration was associated with BALF neutrophil proportions (P?=?.015). Bronchoalveolar lavage fluid mast cell proportions were only associated with respirable ?-glucan exposures (P?=?.030).<h4>Conclusions and clinical importance</h4>Mild equine asthma is common in racing horses and negatively impacts performance. The data support that respirable, rather than inhalable, dust exposure measures are pertinent to equine airway health.
Project description:Rock dusting is used to prevent secondary explosions in coal mines, but inhalation of rock dusts can be hazardous if the crystalline silica (e.g., quartz) content in the respirable fraction is high. The objective of this study is to assess the quartz content and physical characteristics of four selected rock dusts, consisting of limestone or marble in both treated (such as treatment with stearic acid or stearates) and untreated forms. Four selected rock dusts (an untreated and treated limestone and an untreated and treated marble) were aerosolized in an aerosol chamber. Respirable size-selective sampling was conducted along with particle size-segregated sampling using a Micro-Orifice Uniform Deposit Impactor. Fourier Transform Infrared spectroscopy and scanning electron microscopy with energy-dispersive X-ray (SEM-EDX) analyses were used to determine quartz mass and particle morphology, respectively. Quartz percentage in the respirable dust fraction of untreated and treated forms of the limestone dust was significantly higher than in bulk samples, but since the bulk percentage was low the enrichment factor would not have resulted in any major change to conclusions regarding the contribution of respirable rock dust to the overall airborne quartz concentration. The quartz percentage in the marble dust (untreated and treated) was very low and the respirable fractions showed no enrichment. The spectra from SEM-EDX analysis for all materials were predominantly from calcium carbonate, clay, and gypsum particles. No free quartz particles were observed. The four rock dusts used in this study are representative of those presented for use in rock dusting, but the conclusions may not be applicable to all available materials.
Project description:The study assesses the contamination, classification and phytotoxicity of foundry waste. The presented results are a part of the research on the agrotechnical use of foundry waste. Landfilled foundry waste (LFW) and dust samples were taken from one of the Polish foundries. An analysis of the waste and its leachate composition was conducted. Phytotoxicity tests were carried out using Lepidium sativum. The aim of the phytotoxicity study was to evaluate germination and root growth after 72?h and the accumulation of heavy metals after 7 days. LFW was least contaminated with heavy metals and metalloids compared to dust. The composition of the foundry dusts depended on the unit of the foundry, from which it was collected. It was found that electric arc furnace dust (EAFD) was the most polluted by heavy metals among the dust samples. According to the requirements of Polish regulations most of tested waste were classified as non-hazardous, and EAFD as hazardous waste due to high Pb concentration in leachate. Phytotoxicity tests have shown a low phytotoxicity of the leachate from most of the tested waste. The results of the accumulation test showed that an excess of metal and metalloids in leachate was not directly related to its accumulation in plants. A negative correlation between EC, Cu, Co, Fe, Pb, Cr, K, Na, sulfate, fluoride, ammonia, phenol and formaldehyde concentration in leachate and GI was found. It was stated that the Fe, Mn, As and Se in plants was significantly correlated with concentrations in leachate.
Project description:Exposure to organic dusts is associated with increased respiratory morbidity and mortality in agricultural workers. Organic dusts in dairy farm environments are complex, polydisperse mixtures of toxic and immunogenic compounds. Previous toxicological studies focused primarily on exposures to the respirable size fraction; however, organic dusts in dairy farm environments are known to contain larger particles. Given the size distribution of dusts from dairy farm environments, the nasal and bronchial epithelia represent targets of agricultural dust exposures. In this study, well-differentiated normal human bronchial epithelial cells and human nasal epithelial cells were exposed to two different size fractions (PM10 and PM>10) of dairy parlor dust using a novel aerosol-to-cell exposure system. Levels of proinflammatory transcripts (interleukin [IL]-8, IL-6, and tumor necrosis factor [TNF]-?) were measured 2 h after exposure. Lactate dehydrogenase (LDH) release was also measured as an indicator of cytotoxicity. Cell exposure to dust was measured in each size fraction as a function of mass, endotoxin, and muramic acid levels. To our knowledge, this is the first study to evaluate the effects of distinct size fractions of agricultural dust on human airway epithelial cells. Our results suggest that both PM10 and PM>10 size fractions elicit a proinflammatory response in airway epithelial cells and that the entire inhalable size fraction needs to be considered when assessing potential risks from exposure to agricultural dusts. Further, data suggest that human bronchial cells respond differently to these dusts than human nasal cells, and therefore that the two cell types need to be considered separately in airway cell models of agricultural dust toxicity.
Project description:Background:Dust exposure at quarry mines is inevitable and can result in poor air quality. This research aimed to assess pulmonary symptoms and lung functions of dust-exposed workers at an iron-ore mine in eastern Iran. Methods:An environmental cross-sectional study sampled 174 dust-exposed mine workers and 93 unexposed administrative employees as the reference group. A standardized questionnaire on respiratory symptoms was completed in accordance with recommendations of the American Thoracic Society(ATS). Calibrated spirometer measured Pulmonary Function Tests (PFTs). Data were analyzed via SPSS-21, integrating independent samples t-test, Chi-square and linear or logistic-regression models. Results:There was no significant variation between dust-exposed and reference groups in terms of age, weight, height, work experience and the number of smokers (P>0.05). Mean levels of exposure to inhalable and respirable mineral-dust were 15.09±2.34 and 3.45±2.57 mg/m3 respectively. Pulmonary capacities of dust-exposed group were considerably decreased as compared to others (Forced Vital Capacity [FVC] 86.55±13.77 vs. 105.05±21.5; Forced Expiratory Volume in 1 second [FEV1] 88.06±16.8 vs. 105.81±21.55; FEV1/FVC 103.03±18.17 vs. 93.3±12.49; and Peak Expiratory Flow [PEF] 89.82±22.58 vs. 98.09±20.60) (P<0.001); with a higher prevalence of cough (P=0.041), wheezing (P=0.032), and dyspnea (P=0.035) among formers. Age along with exposure to respirable-dust significantly reduced FVC, FEV1 and FEV1/FVC. Cigarette consumption attenuated FVC and FEV1 on an average of 5 to 9 units. Conclusion:Controlled occupational dust-exposure is a definitive pre-requisite to reduce respiratory problems among quarry workers, with an explicit consideration towards mineral- mine workers. Modifiable accomplices like smoking and non-compliance of PPEs usage should be amicably resolved.