ABSTRACT
OBJECTIVES: Pleural mesothelioma is a rare respiratory cancer, mainly caused by inhalation of asbestos fibres. Other inorganic fibres are also suggested risk factors. We aimed to investigate the association between exposure to asbestos or refractory ceramic fibres (RCFs) and pleural mesothelioma among male Norwegian offshore petroleum workers. METHODS: Among 25 347 men in the Norwegian Offshore Petroleum Workers (NOPW) cohort (1965-1998), 43 pleural mesothelioma cases were identified through the Cancer Registry of Norway (1999-2022). A case-cohort study was conducted with 2095 randomly drawn non-cases from the cohort. Asbestos and RCF exposures were assessed with expert-made job-exposure matrices (JEMs). Weighted Cox regression was used to estimate HRs and 95% CIs, adjusted for age at baseline and pre-offshore employment with likely asbestos exposure. RESULTS: An increased risk of pleural mesothelioma was indicated for the highest versus lowest tertile of average intensity of asbestos (HR=1.21, 95% CI: 0.57 to 2.54). Pre-offshore asbestos exposure (vs no such exposure) was associated with increased risk of pleural mesothelioma (HR=2.06, 95% CI: 1.11 to 3.81). For offshore workers with no pre-offshore asbestos exposure, an increased risk of pleural mesothelioma was found for the highest tertile of average intensity of asbestos (HR=4.13, 95% CI: 0.93 to 18), versus the lowest tertile. No associations were found between RCF and pleural mesothelioma. CONCLUSIONS: Associations between JEM-based offshore asbestos exposure and pleural mesothelioma were confirmed in the NOPW cohort. Pleural mesothelioma risk was also associated with asbestos exposure before work in the offshore petroleum industry.
Subject(s)
Asbestos , Ceramics , Mesothelioma , Occupational Diseases , Occupational Exposure , Petroleum , Pleural Neoplasms , Humans , Norway/epidemiology , Occupational Exposure/adverse effects , Male , Asbestos/adverse effects , Middle Aged , Mesothelioma/epidemiology , Mesothelioma/etiology , Mesothelioma/chemically induced , Pleural Neoplasms/epidemiology , Pleural Neoplasms/etiology , Pleural Neoplasms/chemically induced , Occupational Diseases/epidemiology , Occupational Diseases/chemically induced , Occupational Diseases/etiology , Adult , Aged , Ceramics/adverse effects , Petroleum/adverse effects , Cohort Studies , Mesothelioma, Malignant/epidemiology , Mesothelioma, Malignant/etiology , Risk Factors , Oil and Gas Industry , Lung Neoplasms/epidemiology , Lung Neoplasms/etiology , Lung Neoplasms/chemically induced , Mineral Fibers/adverse effects , Case-Control Studies , Proportional Hazards ModelsABSTRACT
BACKGROUND: Inhalation of biopersistent fibers like asbestos can cause strong chronic inflammatory effects, often resulting in fibrosis or even cancer. The interplay between fiber shape, fiber size and the resulting biological effects is still poorly understood due to the lack of reference materials. RESULTS: We investigated how length, diameter, aspect ratio, and shape of synthetic silica fibers influence inflammatory effects at doses up to 250 µg cm-2. Silica nanofibers were prepared with different diameter and shape. Straight (length ca. 6 to 8 µm, thickness ca. 0.25 to 0.35 µm, aspect ratio ca. 17:1 to 32:1) and curly fibers (length ca. 9 µm, thickness ca. 0.13 µm, radius of curvature ca. 0.5 µm, aspect ratio ca. 70:1) were dispersed in water with no apparent change in the fiber shape during up to 28 days. Upon immersion in aqueous saline (DPBS), the fibers released about 5 wt% silica after 7 days irrespectively of their shape. The uptake of the fibers by macrophages (human THP-1 and rat NR8383) was studied by scanning electron microscopy and confocal laser scanning microscopy. Some fibers were completely taken up whereas others were only partially internalized, leading to visual damage of the cell wall. The biological effects were assessed by determining cell toxicity, particle-induced chemotaxis, and the induction of gene expression of inflammatory mediators. CONCLUSIONS: Straight fibers were only slightly cytotoxic and caused weak cell migration, regardless of their thickness, while the curly fibers were more toxic and caused significantly stronger chemotaxis. Curly fibers also had the strongest effect on the expression of cytokines and chemokines. This may be due to the different aspect ratio or its twisted shape.
Subject(s)
Chemotaxis , Macrophages , Particle Size , Silicon Dioxide , Silicon Dioxide/toxicity , Silicon Dioxide/chemistry , Animals , Humans , Rats , Macrophages/drug effects , Macrophages/metabolism , Chemotaxis/drug effects , Nanofibers/toxicity , Nanofibers/chemistry , THP-1 Cells , Transcriptome/drug effects , Mineral Fibers/toxicity , Cytokines/metabolism , Cytokines/genetics , Cell LineABSTRACT
Asbestos fibres have been considered an environmental hazard for decades. However, little is known about the attempts of circulating immune cells to counteract their toxicity. We addressed the early effects of fibre-released soluble factors (i.e. heavy metals) in naïve immune cells, circulating immediately below the alveolar/endothelial cell layer. By comparison, the direct fibre effects on endotheliocytes were also studied since these cells are known to sustain inflammatory processes. The three mineral fibres analysed showed that mainly chrysotile (CHR) and erionite (ERI) were able to release toxic metals in extracellular media respect to crocidolite (CRO), during the first 24 h. Nevertheless, all three fibres were able to induce oxidative stress and genotoxic damage in indirectly challenged naïve THP-1 monocytes (separated by a membrane). Conversely, only CHR-released metal ions induced apoptosis, NF-κB activation, cytokines and CD163 gene overexpression, indicating a differentiation towards the M0 macrophage phenotype. On the other hand, all three mineral fibres in direct contact with HECV endothelial cells showed cytotoxic, genotoxic and apoptotic effects, cytokines and ICAM-I overexpression, indicating the ability of these cells to promote an inflammatory environment in the lung independently from the type of inhaled fibre. Our study highlights the different cellular responses to mineral fibres resulting from both the nature of the cells and their function, but also from the chemical-physical characteristics of the fibres. In conclusion, CHR represented the main pro-inflammatory trigger, able to recruit and activate circulating naïve monocytes, through its released metals, already in the first 24 h after inhalation.
Subject(s)
Mineral Fibers , Humans , Mineral Fibers/toxicity , Oxidative Stress/drug effects , Apoptosis/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , DNA Damage/drug effects , Asbestos, Serpentine/toxicity , THP-1 Cells , Cytokines/metabolism , Inflammation/chemically induced , Monocytes/drug effects , Monocytes/metabolism , Metals, Heavy/toxicity , NF-kappa B/metabolism , Cell Line , Asbestos, Crocidolite/toxicity , ZeolitesABSTRACT
Chronic inflammation induced in vivo by mineral fibres, such as asbestos, is sustained by the cyclic formation of cytotoxic/genotoxic oxidant species that are catalysed by iron. High catalytic activity is observed when iron atoms are isolated in the crystal lattice (nuclearity=1), whereas the catalytic activity is expected to be reduced or null when iron forms clusters of higher nuclearity. This study presents a novel approach for systematically measuring iron nuclearity across a large range of iron-containing standards and mineral fibres of social and economic importance, and for quantitatively assessing the relation between nuclearity and toxicity. The multivariate curve resolution (MCR) empirical approach and density functional theory (DFT) calculations were applied to the analysis of UV-Vis spectra to obtain information on the nature of iron and nuclearity. This approach led to the determination of the nuclearity of selected mineral fibres which was subsequently used to calculate a toxicity-related index. High nuclearity-related toxicity was estimated for chrysotile samples, fibrous glaucophane, asbestos tremolite, and fibrous wollastonite. Intermediate values of toxicity, corresponding to a mean nuclearity of 2, were assigned to actinolite asbestos, amosite, and crocidolite. Finally, a low nuclearity-related toxicity parameter, corresponding to an iron-cluster with a lower catalytic power to produce oxidants, was assigned to asbestos anthophyllite.
Subject(s)
Asbestos , Iron , Mineral Fibers/toxicity , Mineral Fibers/analysis , Asbestos/toxicity , Asbestos, Serpentine , Asbestos, Crocidolite , OxidantsABSTRACT
OBJECTIVES: In Italy, the highest pleural cancer mortality and incidence have been observed among Italian regions where the 2 largest Italian shipyards were (and are) located. The objective of this study was to assess the exposure-response relationship for mesothelioma among male workers employed in the Monfalcone, Italy, shipyard. METHODS: We conducted a necropsy-based case-control study. Cases (N = 102) were mesothelioma decedents and controls were those with lung cancer (N = 84). Complete job histories were available; the lung fibre content was measured using a scanning electron microscope with X-ray fluorescence, after sample preparation according to the European Respiratory Society guidelines. Odds ratios and 95% confidence intervals of mesothelioma by fibre type and lung fibre burden, as a categorical or continuous variable, were assessed by unconditional logistic regression, adjusted for age and time since exposure cessation. Analyses for the amphibole and chrysotile lung fibre burden were mutually adjusted. We calculated a cumulative exposure index by applying a job-exposure matrix to the job histories of study cases and assessed its correlation with the lung fibre burden. RESULTS: We found an odds ratio of 22.0 (confidence intervals 5.66-85.7) for the highest lung fibre burden category (mean 43.8 million total asbestos fibres per gram of dry tissue) compared with the reference (mean 0.48). Using log10-transformed lung fibre burden, we found that the odds ratio was 3.71 (confidence intervals 2.03-6.79) for a 10-fold lung fibre burden increase. Results for the amphibole lung fibre burden were similar. Odds ratios increased over chrysotile lung fibre burden categories (P-trend = 0.025), and the odds ratio for a 10-fold increase was 4.73 (confidence intervals 0.32-70.4). CONCLUSIONS: The cumulative exposure index was correlated with total and amphibole lung fibre burden, but not with chrysotile lung fibre burden. Mesothelioma risk was proportional to total, amphibole, and chrysotile lung fibre burden in shipyard workers.
Subject(s)
Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Occupational Exposure , Ships , Humans , Male , Case-Control Studies , Occupational Exposure/adverse effects , Mesothelioma/pathology , Mesothelioma/etiology , Mesothelioma/epidemiology , Italy/epidemiology , Middle Aged , Lung Neoplasms/pathology , Lung Neoplasms/etiology , Lung Neoplasms/epidemiology , Aged , Mineral Fibers/analysis , Mineral Fibers/adverse effects , Occupational Diseases/epidemiology , Occupational Diseases/etiology , Lung/pathology , Pleural Neoplasms/etiology , Pleural Neoplasms/pathology , Pleural Neoplasms/epidemiology , Adult , Odds Ratio , Autopsy , Asbestos/analysis , Asbestos/adverse effects , Asbestos, Amphibole/analysis , Asbestos, Amphibole/adverse effects , Asbestos, Serpentine/analysis , Asbestos, Serpentine/adverse effects , Risk FactorsABSTRACT
Asbestos has been widely used due to its unique characteristics. It is known that exposure to asbestos causes serious damage to health but one species, chrysolite, is still used because it is considered less toxic and not biopersistent in some countries. The aim of our study was to investigate if cellular process underlying the proliferation, differentiation and cell death of placental tissues could be modify in presence of asbestos fibres (50 µg/ml final concentration), long chrysolite fibres (CHR-L) and short chrysolite fibres (CHR-S), using BeWo cell line, an in vitro model that mimics the syncytiotrophoblast (STB), the outer layer of placental villi. Our data demonstrated that none of the fibres analysed alter syncytiotrophoblast formation but all of them induce ROS formation and reduced cell proliferation. Moreover, we showed that only CHR-L fibre induced was able to induce irreversible DNA alterations that carried cells to apoptosis. In fact, BeWo cells exposed to CHR-L fibre showed a significant increase in cleaved CASP3 protein, a marker of apoptosis. These data suggest that CHR-L may induce death of the placental villi leading to impaired placental development. The impairment of placental development is the basis of many gestational pathologies such as preeclampsia and intrauterine growth retardation. Since these pathologies are very dangerous for foetal and maternal life, we suggest to the gynaecologists to carefully evaluate the area of maternal residence, the working environment, the food used, and the materials used daily to avoid contact with these fibres as much as possible.
Subject(s)
Asbestos , Placenta , Humans , Pregnancy , Female , Mineral Fibers/toxicity , Trophoblasts/metabolism , Asbestos/metabolism , Asbestos/toxicity , ApoptosisABSTRACT
BACKGROUND: Exposure to asbestos is associated with malignant and nonmalignant respiratory disease. To strengthen the scientific basis for risk assessment on fibers, the National Institute of Environmental Health Sciences (NIEHS) has initiated a series of studies to address fundamental questions on the toxicology of naturally occurring asbestos and related mineral fibers after inhalation exposure. A prototype nose-only exposure system was previously developed and validated. The prototype system was expanded to a large-scale exposure system in this study for conducting subsequent in vivo rodent inhalation studies of Libby amphibole (LA) 2007, selected as a model fiber. RESULTS: The exposure system consisting of six exposure carousels was able to independently deliver stable LA 2007 aerosol to individual carousels at target concentrations of 0 (control group), 0.1, 0.3, 1, 3, or 10 mg/m3. A single aerosol generator was used to provide aerosol to all carousels to ensure that exposure atmospheres were chemically and physically similar, with aerosol concentration as the only major variable among the carousels. Transmission electron microscopy (TEM) coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis of aerosol samples collected at the exposure ports indicated the fiber dimensions, chemical composition, and mineralogy were equivalent across exposure carousels and were comparable to the bulk LA 2007 material. CONCLUSION: The exposure system developed is ready for use in conducting nose-only inhalation toxicity studies of LA 2007 in rats. The exposure system is anticipated to have applicability for the inhalation toxicity evaluation of other natural mineral fibers of concern.
Subject(s)
Asbestos, Amphibole , Asbestos , Rats , Animals , Asbestos, Amphibole/toxicity , Mineral Fibers , Aerosols , Inhalation Exposure/adverse effectsABSTRACT
BACKGROUND: Asbestos has been classified as a human carcinogen, and exposure may increase the risk of diseases associated with impaired respiratory function. As the range of health effects and airborne concentrations that result in health effects across asbestos-related natural mineral fiber types are not fully understood, the National Institute of Environmental Health Sciences has established a series of research studies to characterize hazards of natural mineral fibers after inhalation exposure. This paper presents the method development work of this research project. RESULTS: A prototype nose-only exposure system was fabricated to explore the feasibility of generating natural mineral fiber aerosol for in vivo inhalation toxicity studies. The prototype system consisted of a slide bar aerosol generator, a distribution/delivery system and an exposure carousel. Characterization tests conducted using Libby Amphibole 2007 (LA 2007) demonstrated the prototype system delivered stable and controllable aerosol concentration to the exposure carousel. Transmission electron microscopy (TEM) analysis of aerosol samples collected at the exposure port showed the average fiber length and width were comparable to the bulk LA 2007. TEM coupled with energy dispersive spectrometry (EDS) and selected area electron diffraction (SAED) analysis further confirmed fibers from the aerosol samples were consistent with the bulk LA 2007 chemically and physically. CONCLUSIONS: Characterization of the prototype system demonstrated feasibility of generating LA 2007 fiber aerosols appropriate for in vivo inhalation toxicity studies. The methods developed in this study are suitable to apply to a multiple-carousel exposure system for a rat inhalation toxicity testing using LA 2007.
Subject(s)
Asbestos, Amphibole , Asbestos , Humans , Rats , Animals , Asbestos, Amphibole/toxicity , Mineral Fibers , Asbestos/analysis , Carcinogens/toxicity , AerosolsABSTRACT
CONTEXT: Excess mesothelioma risk was observed among chrysotile miners and millers in Balangero, Italy. The mineral balangeroite has been identified in an asbestiform habit from the Balangero chrysotile mine (Italy). Previous studies did not contain a detailed description of the fiber dimensions, thus limiting possible approaches to estimating their carcinogenic potential. OBJECTIVES: To reconstruct excess mesothelioma risk based on characteristics of mixed fiber exposure. METHODS: The lengths and widths of particles from a sample of balangeroite were measured by transmission electron microscopy (TEM). Statistical analysis and modeling were applied to assess the toxicological potential of balangeroite. RESULTS: Balangeroite fibers are characterized as asbestiform, with geometric mean length of 10 µm, width of 0.54 µm, aspect ratio of 19, and specific surface area of 13.8 (1/µm). Proximity analysis shows dimensional characteristics of balangeroite close to asbestiform anthophyllite. Modeling estimates the average potency of balangeroite as 0.04% (95% CI 0.0058, 0.16) based on dimensional characteristics and 0.05% (95% CI-0.04, 0.24) based on epidemiological data. The available estimate of the fraction of balangeroite in the Balangero mine is very approximate. There were no data for airborne balangeroite fibers from the Balangero mine and no lung burden data are available. All estimates were performed using weight fractions of balangeroite and chrysotile. However, based on reasonable assumptions, of the seven cases of mesothelioma in the cohort, about three cases (43%) can be attributed to fibrous balangeroite. CONCLUSION: The presence of different types of mineral fibers in aerosolized materials even in small proportions can explain observed cancer risks.
Subject(s)
Asbestos , Lung Neoplasms , Mesothelioma, Malignant , Mesothelioma , Humans , Asbestos, Serpentine/toxicity , Mineral Fibers/toxicity , Carcinogens/toxicity , Asbestos, Amphibole/toxicity , Mesothelioma/chemically induced , Mesothelioma/epidemiology , Lung Neoplasms/chemically induced , Lung Neoplasms/epidemiology , Asbestos/analysisABSTRACT
Mineral wool fibers can be released into the air during the production and handling of a mineral wool product where a small fraction of fibers will stay airborne and can potentially be inhaled. The aerodynamic fiber diameter determines how far an airborne fiber can pass through the human airway. Respirable fibers with an aerodynamic diameter < 3 µm can reach the deep part of the lungs (i.e., the alveolar region). Binder material (i.e., organic binder and mineral oil) is used in the production of mineral wool products. However, at the current stage, it is unknown if airborne fibers can contain binder material. We explored binder presence on airborne respirable fiber fractions being released and collected during the installation of two mineral wool products (a stone wool product and a glass wool product). Fiber collection was done by pumping a controlled air volume (2, 13, 22, and 32 l/min) through polycarbonate membrane filters during the installation of the mineral wool products. The morphological and chemical composition of the fibers were studied using scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDXS) analysis. The study demonstrates that binder material is found on the surface of the respirable mineral wool fiber mainly as circular or elongated droplets. Our findings suggest that respirable fibers explored in previous epidemiological studies, which have been used for proving a lack of hazardous effects of mineral wool on humans, may have also contained binder materials on the fibers.
Subject(s)
Mineral Fibers , Silicates , Humans , Minerals , GlassABSTRACT
CONTEXT: Based on a decade-long exploration, dimensions of elongate mineral particles are implicated as a pivotal component of their carcinogenic potency. This paper summarizes current understanding of the discovered relationships and their importance to the protection of public health. OBJECTIVES: To demonstrate the relationships between cancer risk and dimensions (length, width, and other derivative characteristics) of mineral fibers by comparing the results and conclusions of previously published studies with newly published information. METHODS: A database including 59 datasets comprising 341,949 records were utilized to characterize dimensions of elongate particles. The descriptive statistics, correlation and regression analysis, combined with Monte Carlo simulation, were used to select dimensional characteristics most relevant for mesothelioma and lung cancer risk prediction. RESULTS: The highest correlation between mesothelioma potency factor and weight fraction of size categories is achieved for fibers with lengths >5.6 µm and widths ≤0.26 µm (R = 0.94, P < 0.02); no statistically significant potency was found for lengths <5 µm. These results are consistent with early published estimations, though are derived from a different approach. For combinations of amphiboles and chrysotile (with a consideration of a correction factor between mineral classes), the potency factors correlated most highly with a fraction of fibers longer than 5 µm and thinner than 0.2 µm for mesothelioma, and longer than 5 µm and thinner than 0.3 µm for lung cancer. Because the proportion of long, thin particles in asbestiform vs. non-asbestiform dusts is higher, the cancer potencies of the former are predicted at a significantly higher level. The analysis of particle dimensionality in human lung burden demonstrates positive selection for thinner fibers (especially for amosite and crocidolite) and prevailing fraction of asbestiform habit. CONCLUSION: Dimensions of mineral fibers can be confirmed as one of the main drivers of their carcinogenicity. The width of fibers emerges as a primary potency predictor, and fibers of all widths with lengths shorter than 5 µm seem to be non-impactful for cancer risk. The mineral dust with a fibrous component is primarily carcinogenic if it contains amphibole fibers longer than 5 µm and thinner than 0.25 µm.
Subject(s)
Asbestos , Lung Neoplasms , Mesothelioma , Humans , Mineral Fibers/toxicity , Minerals/toxicity , Minerals/analysis , Mesothelioma/chemically induced , Mesothelioma/epidemiology , Asbestos, Amphibole , Lung Neoplasms/chemically induced , Lung Neoplasms/epidemiology , Carcinogens/analysis , Dust/analysisABSTRACT
This study aimed to systematically review and synthesize epidemiological evidence evaluating the association between occupational man-made vitreous fiber (MMVF) exposure and non-malignant respiratory disease (NMRD). We searched PubMed and Scopus databases to identify epidemiological studies evaluating the association between occupational MMVF exposure (limited to insulation wools) and at least 1 NMRD outcome published prior to January 2023. A total of 23 studies met our inclusion criteria. Studies of NMRD mortality among workers with MMVF exposure (n = 9) predominately reported null findings. Qualitative and quantitative synthesis of evidence from these studies suggests that MMVF exposure is not associated with elevated risk of NMRD mortality. The remaining 14 studies evaluated NMRD morbidity, specifically self-reported respiratory symptoms and/or subclinical measures of respiratory disease. Our review did not identify any consistent or compelling evidence of an association between MMVF exposure and any NMRD morbidity outcome; however, this body of evidence was largely limited by cross-sectional design, self-reported exposure and/or outcome ascertainment, incomplete statistical analysis and reporting, and questionable generalizability given that 13/14 studies were published over 20 years ago. We recommend that future studies aim to overcome the limitations of this literature to more accurately characterize the association between occupational MMVF exposure and NMRD morbidity.
Subject(s)
Occupational Diseases , Occupational Exposure , Respiratory Tract Diseases , Animals , Humans , Cross-Sectional Studies , Respiratory Tract Diseases/chemically induced , Respiratory Tract Diseases/epidemiology , Occupational Exposure/adverse effects , Epidemiologic Studies , Occupational Diseases/chemically induced , Occupational Diseases/epidemiology , Mineral Fibers/adverse effectsABSTRACT
OBJECTIVE: We developed predictive formulae for the in vitro dissolution rate constant kdis of acid-soluble synthetic vitreous fibers (SVF), paralleling our earlier work with glass wools, which are typically more soluble at neutral pH. Developing simple models for predicting the kdis of a fiber can allow prediction of in vivo behavior, aid fiber developers, and potentially reduce in vivo testing. METHODS: The kdis of several acid-soluble SVF were determined using high simulant fluid flow/fiber surface area (F/A) conditions via a single-fiber measurement system. Four fluids were employed, varying in base composition and citrate levels. Equations predicting the kdis were derived from fiber chemistry and dissolution measurements for two of the fluids. RESULTS: Testing of several fibers showed a â¼10× increase in the kdis when citrate was included in the simulant solution. Data from tests with Stefaniak's citrate-free Phagoloysosmal Simulant Fluid (PSF) yielded kdis values aligned with expectations from in vivo results, unlike results from citrate-containing modified Gamble's solution. Predictive equations relating fiber chemistry to kdis showed reasonable agreement between the measured and predicted values. CONCLUSIONS: Citrate inclusion in the solution under high F/A conditions significantly increased the measured kdis. This resulted in more biorelevant data being obtained using the PSF fluid with the high F/A method used. The developed predictive equations, sufficient for fiber development work, require refinement before a recommending their use in place of in vivo biopersistence testing. Significant fit improvements are possible through additional measurements under these experimental conditions.
Subject(s)
Mineral Fibers , Silicates , Solubility , Minerals/chemistry , Glass/chemistry , Citric AcidABSTRACT
This work reviews the bio-chemical mechanisms leading to adverse effects produced when mineral fibres are inhaled and transported in the lungs from the perspective of a mineralogist. The behaviour of three known carcinogenic mineral fibres (crocidolite, chrysotile, and fibrous-asbestiform erionite) during their journey through the upper respiratory tract, the deep respiratory tract and the pleural cavity is discussed. These three fibres have been selected as they are the most socially and economically relevant mineral fibres representative of the classes of chain silicates (amphiboles), layer silicates (serpentine), and framework silicates (zeolites), respectively. Comparison of the behaviour of these fibres is made according to their specific crystal-chemical assemblages and properties. Known biological and subsequent pathologic effects which lead and contribute to carcinogenesis are critically reviewed under the mineralogical perspective and in relation to recent progress in this multidisciplinary field of research. Special attention is given to the understanding of the cause-effect relationships for lung cancer and malignant mesothelioma. Comparison with interstitial pulmonary fibrosis, or "asbestosis", will also be made here. This overview highlights open issues, data gaps, and conflicts in the literature for these topics, especially as regards relative potencies of the three mineral fibres under consideration for lung cancer and mesothelioma. Finally, an attempt is made to identify future research lines suitable for a general comprehensive model of the carcinogenicity of mineral fibres.
Subject(s)
Asbestos , Lung Neoplasms , Zeolites , Humans , Mineral Fibers/toxicity , Asbestos, Crocidolite , Asbestos, Serpentine , Zeolites/chemistry , Asbestos, Amphibole/toxicity , Lung , Lung Neoplasms/chemically induced , Asbestos/toxicityABSTRACT
Alveolar macrophages are the first line of defence against detrimental inhaled stimuli. To date, no comparative data have been obtained on the inflammatory response induced by different carcinogenic mineral fibres in the three main macrophage phenotypes: M0 (non-activated), M1 (pro-inflammatory) and M2 (alternatively activated). To gain new insights into the different toxicity mechanisms of carcinogenic mineral fibres, the acute effects of fibrous erionite, crocidolite and chrysotile in the three phenotypes obtained by THP-1 monocyte differentiation were investigated. The three mineral fibres apparently act by different toxicity mechanisms. Crocidolite seems to exert its toxic effects mostly as a result of its biodurability, ROS and cytokine production and DNA damage. Chrysotile, due to its low biodurability, displays toxic effects related to the release of toxic metals and the production of ROS and cytokines. Other mechanisms are involved in explaining the toxicity of biodurable fibrous erionite, which induces lower ROS and toxic metal release but exhibits a cation-exchange capacity able to alter the intracellular homeostasis of important cations. Concerning the differences among the three macrophage phenotypes, similar behaviour in the production of pro-inflammatory mediators was observed. The M2 phenotype, although known as a cell type recruited to mitigate the inflammatory state, in the case of asbestos fibres and erionite, serves to support the process by supplying pro-inflammatory mediators.
Subject(s)
Asbestos , Mineral Fibers , Asbestos/metabolism , Asbestos, Crocidolite/metabolism , Asbestos, Serpentine , Inflammation Mediators/metabolism , Macrophages, Alveolar/metabolism , Mineral Fibers/toxicity , Phenotype , Reactive Oxygen Species/metabolismABSTRACT
Asbestos fibers have been used as an industrial and construction material worldwide due to their high durability and low production cost. Commercial usage of asbestos is currently prohibited in Japan; however, the risk of asbestos-induced malignant mesothelioma (MM) remains. According to epidemiological data, the onset of MM is estimated to occur after a latent period of 30-40 years from initial exposure to asbestos fibers; thus, the continuous increase in MM is a concern. To explore the molecular mechanisms of MM using animal models, iron saccharate with iron chelator-induced sarcomatoid mesothelioma (SM) revealed hallmarks of homozygous deletion of Cdkn2a/2b by aCGH and microRNA-199/214 by expression microarray. Oral treatment of iron chelation by deferasirox decreased the rate of high-grade SM. Moreover, phlebotomy delayed MM development in crocidolite-induced MM in rats. In Divalent metal transporter 1 (Dmt1) transgenic mice, MM development was delayed because of low reactive oxygen species (ROS) production. These results indicate the importance of iron and ROS in mesothelial carcinogenesis. The aims of this review focus on the pathogenesis of elongated mineral particles (EMPs), including asbestos fibers and multiwalled carbon nanotubes (MWCNTs) that share similar rod-like shapes in addition to the molecular mechanisms of MM development.
Subject(s)
Asbestos/adverse effects , Iron/metabolism , Mesothelioma, Malignant/pathology , Mineral Fibers/adverse effects , Nanotubes, Carbon/adverse effects , Reactive Oxygen Species/metabolism , Animals , Asbestos, Crocidolite/adverse effects , Carcinogenesis , Cation Transport Proteins/genetics , Cation Transport Proteins/metabolism , Deferasirox/administration & dosage , Humans , Iron Chelating Agents/administration & dosage , Mesothelioma, Malignant/chemically induced , Mice , Mice, Transgenic , Oxidative StressABSTRACT
Inhalation of mineral fibres is associated with the onset of an inflammatory activity in the lungs and the pleura responsible for the development of fatal malignancies. It is known that cell damage is a necessary step for triggering the inflammatory response. However, the mechanisms by which mineral fibres exert cytotoxic activity are not fully understood. In this work, the kinetics of the early cytotoxicity mechanisms of three mineral fibres (i.e., chrysotile, crocidolite and fibrous erionite) classified as carcinogenic by the International Agency for Research on Cancer, was determined for the first time in a comparative manner using time-lapse video microscopy coupled with in vitro assays. All tests were performed using the THP-1 cell line, differentiated into M0 macrophages (M0-THP-1) and exposed for short times (8 h) to 25 µg/mL aliquots of chrysotile, crocidolite and fibrous erionite. The toxic action of fibrous erionite on M0-THP-1 cells is manifested since the early steps (2 h) of the experiment while the cytotoxicity of crocidolite and chrysotile gradually increases during the time span of the experiment. Chrysotile and crocidolite prompt cell death mainly via apoptosis, while erionite exposure is also probably associated to a necrotic-like effect. The potential mechanisms underlying these different toxicity behaviours are discussed in the light of the different morphological, and chemical-physical properties of the three fibres.
Subject(s)
Apoptosis , Microscopy, Video/methods , Mineral Fibers/toxicity , Reactive Oxygen Species/metabolism , Time-Lapse Imaging/methods , Asbestos, Crocidolite/toxicity , Asbestos, Serpentine/toxicity , Calcium/metabolism , Fluorescent Dyes , Humans , Sodium/metabolism , THP-1 Cells , Zeolites/toxicityABSTRACT
The biopersistence of fiber materials is one of the cornerstones in estimating potential risk to human health upon inhalation. To connect epidemiological and in vivo investigations with in vitro studies, reliable and robust methods of fiber biopersistence determination and understanding of fiber dissolution mechanism are required. We investigated dissolution properties of oil treated stone wool fibers with and without sugar-based binder (SBB) at 37 °C in the liquids representing macrophages intracellular conditions (pH 4.5). Conditions varied from batch to flow of different rates. Fiber morphology and surface chemistry changes caused by dissolution were monitored with scanning electron microscopy and time-of-flight secondary ion mass spectrometry mapping. Stone wool fiber dissolution rate depends on liquid composition (presence of ligands, such as citrate), pH, reaction products transport and fibers wetting properties. The dissolution rate decreases when: 1) citrate is consumed by the reaction with the released Al cations; 2) the pH increases during a reaction in poorly buffered solutions; 3) the dissolution products are accumulated; 4) fibers are not fully wetted with the fluid. Presence of SBB has no influence on dissolution rate if fiber material was wetted prior to dissolution experiment to avoid poorly wetted fiber agglomerates formation in the synthetic lung fluids.
Subject(s)
Mineral Fibers/analysis , Solubility , Lung , Microscopy, Electron, Scanning , Spectrometry, Mass, Secondary Ion , Sugars/chemistryABSTRACT
Extensive toxicology studies of synthetic vitreous fibers (SVFs) demonstrated that fiber dimension, durability/dissolution, and biopersistence are critical factors for risk of fibrogenesis and carcinogenesis. Lessons learned from the SVF experience provide useful context for predicting hazards and risk of nano-enabled advanced materials. This review provides (1) a historical toxicological overview of animal and in vitro toxicology studies of SVFs, (2) key findings that long durable fibers pose a risk of fibrogenic and tumorigenic responses and not short fibers or long soluble fibers, (3) in vitro and in vivo test methods for biodurability and biopersistence and associated predictive thresholds for fibrosis or tumors, and (4) recommendations for testing of advanced materials. Generally, SVFs (fiber lengths >20 µm) with in vitro fiber dissolution rates greater than 100 ng/cm2/hr (glass fibers in pH 7 and stone fibers in pH 4.5) and in vivo fiber clearance less than WT1/2 40 or 50 days were not associated with fibrosis or tumors. Long biodurable and biopersistent fibers exceeding these fiber dissolution and clearance thresholds may pose a risk of fibrosis and cancer. Fiber length-, durability-, and biopersistent-dependent factors that influence pathogenicity of mineral fibers are also expected to affect the biological effects of high aspect ratio nanomaterials (HARN). Only with studies aimed to correlate in vitro durability, in vivo biopersistence, and biological outcomes will it be determined whether similar or different in vitro fiber dissolution and in vivo half-life thresholds, which exempt carcinogenicity classification of SVFs, can also apply to HARNs.
Subject(s)
Lung , Mineral Fibers , Animals , Mineral Fibers/toxicity , Carcinogenesis/pathology , FibrosisABSTRACT
BACKGROUND: Refractory Ceramic fibres (RCF) are man-made mineral fibres used in high performance thermal insulation applications. Analogous to asbestos fibres, RCF are respirable, show a pleural drift and can persist in human lung tissue for more than 20 years after exposure. Pleural changes such as localised or diffuse pleural thickening as well as pleural calcification were reported. RESULT: A 45 years old man worked in high performance thermal insulation applications using refractory ceramic fibres (RCF) for almost 20 years. During a occupational medical prophylaxis to ensure early diagnosis of disorders caused by inhalation of aluminium silicate fibres with X-ray including high-resolution computed tomography (HRCT), bilateral pleural thickening was shown and a pleural calcification next to a rounded atelectasis was detected. Asbestos exposure could be excluded. In pulmonary function test a restrictive lung pattern could be revealed. In work samples scanning electron microscopy (SEM) including energy dispersive X-ray analysis (EDX) classified used fibres as aluminium silicate fibres. X-ray powder diffraction (XRD) and transmission electron microscopy (TEM) showed crystalline as well as amorphous fibres. CONCLUSIONS: A comprehensive lung function analysis and in case of restrictive lung disorders additional CT scans are needed in RCF exposed workers in accordance to the guidelines for medical occupational examinations comparable to asbestos exposed workers.