Recognizing the pleura in asbestos-related pleuropulmonary disease: Known and new manifestations of pleural fibrosis.

Pleural thickening (PT) is a major consequence of exposure to all fiber types of asbestos. In recent decades, it is more prevalent than parenchymal asbestosis. Its manifestations occupy a full clinical and radiographic spectrum. Six major manifestations can be identified: (a) acute pleuritis generally with effusion; (b) diffuse PT or fibrous pleuritis; (c) rounded atelectasis; (d) circumscribed PT or plaques; (e) chronic pleuritic pain; and (f) mesothelioma. Review of the experience of workers and community members in Libby, MT to asbestiform fibers in vermiculite has confirmed the appearance of these previously known benign and malignant asbestos-related diseases as well as a unique pleuropulmonary disease characterized as lamellar PT and associated with progressive decline in pulmonary function and pleuritic pain. Despite previous literature asserting that PT represents a marker for asbestos exposure without significant effect on pulmonary function and physiology, the experience of Libby amphibole (LA) disease, along with other studies, indicates that PT plays a role in declining vital capacity in those with prolonged or unusual exposures such as those arising from LA.

The diagnosis of asbestosis in the 21st century: a clinicopathological correlation of 102 cases.

Asbestosis, defined as diffuse pulmonary fibrosis caused by inhalation of asbestos fibers, occurs after heavy exposures to asbestos dust over several decades. Because workplace exposures have been significantly curtailed since the banning of asbestos in insulation products, we were interested in examining the clinicopathological characteristics of cases diagnosed in the 21st century. The consultation files of one of the authors (VLR) were reviewed for cases of asbestosis diagnosed since 1/1/2001. 102 cases were identified, with a median age of 75 years (range: 45-89). There were 100 men and 2 women. The women were from Turkey and Brazil (none from the United States). Malignancies were present in 78 cases, including 38 lung cancers, 29 pleural mesotheliomas, and 8 peritoneal mesotheliomas. The grade of asbestosis was available in 88 cases (median severity of 2; scale: 1-4). Pleural plaque was present in 94% of cases. The most common exposure categories were insulators (39), shipyard workers (16), asbestos manufacturing (9), boiler workers (8) and pipefitter/welders (6). The median duration of exposure was 33 years (range: 2-49 years). Lung fiber burden analysis was performed in 34 cases, with amosite being the predominant fiber type. Results were compared with similar information for 475 cases diagnosed prior to 1/1/2001.

A review of the mesotheliogenic potency of cleavage fragments found in talc.

It has long been recognized that amphibole minerals, such as cleavage fragments of tremolite and anthophyllite, may exist in some talc deposits. We reviewed the current state of the science regarding the factors influencing mesotheliogenic potency of cleavage fragments, with emphasis on those that may co-occur in talc deposits, including dimensional and structural characteristics, animal toxicology, and the most well-studied cohort exposed to talc-associated cleavage fragments. Based on our review, multiple lines of scientific evidence demonstrate that inhaled cleavage fragments associated with talc do not pose a mesothelioma hazard.

Cr5.7Si2.3P8N24-A Chromium(+IV) Nitridosilicate Phosphate with Amphibole-Type Structure.

The first nitridic analog of an amphibole mineral, the quaternary nitridosilicate phosphate Cr5.7Si2.3P8N24 was synthesized under high-pressure high-temperature conditions at 1400 °C and 12 GPa from the binary nitrides Cr2N, Si3N4 and P3N5, using NH4N3 and NH4F as additional nitrogen source and mineralizing agent, respectively. The crystal structure was elucidated by single-crystal X-ray diffraction with microfocused synchrotron radiation (C2/m, a=9.6002(19), b=17.107(3), c=4.8530(10) Å, ß=109.65(3)°). The elemental composition was analyzed by energy dispersive X-ray spectroscopy. The structure consists of vertex-sharing PN4-tetrahedra forming zweier double chains and edge-sharing (Si,Cr)-centered octahedra forming separated ribbons. Atomic resolution scanning transmission electron microscopy shows ordered Si and Cr sites next to a disordered Si/Cr site. Optical spectroscopy indicates a band gap of 2.1 eV. Susceptibility measurements show paramagnetic behavior and support the oxidation state Cr+IV, which is confirmed by EPR. The comprehensive analysis expands the field of Cr-N chemistry and provides access to a nitride analog of one of the most prevalent silicate structures.

Alkaline magmas in shallow arc plutonic roots: a field and experimental investigation of hydrous cumulate melting in the southern Adamello batholith.

Despite the first-order importance of crystallisation-differentiation for arc magma evolution, several other processes contribute to their compositional diversity. Among them is the remelting of partly crystallised magmas, also known as cumulate melting or 'petrological cannibalism'. The impact of this process on the plutonic record is poorly constrained. We investigate a nepheline-normative dyke suite close to the Blumone gabbros, a large amphibole-gabbro unit of the Tertiary Southern Alpine Adamello igneous complex. The compositions of the studied dykes are characterised by low SiO2 (43-46 wt. %), MgO (5.0-7.2 wt. %), Ni (18-40 µg/g), and high Al2O3 (20.2-22.0 wt. %) contents. Phenocrystic plagioclase in these dykes exhibits major, trace, and Sr isotope compositions similar to Blumone cumulate plagioclase, suggesting a genetic link between the nepheline-normative dykes and the amphibole-gabbro cumulates. We tested this hypothesis by performing saturation experiments on a nepheline-normative dyke composition in an externally heated pressure vessel at 200 MPa between 975 and 1100 °C at fO2 conditions close to the Ni-NiO buffer. Plagioclase and spinel are near-liquidus phases at and above 1050 °C, contrasting with the typical near-liquidus olivine ± spinel assemblage in hydrous calc-alkaline basalts. The alkaline nature of the dykes results from the abundance of amphibole in the protolith, consistent with melting of amphibole-gabbro cumulates. We modelled the heat budget from the repeated injection of basaltic andesite into a partly crystallised amphibole-gabbro cumulate. The results of this model show that no more than 7% of the cumulate pile reaches temperatures high enough to produce nepheline-normative melts. We propose that such nepheline-normative dykes are a hallmark of hydrous cumulate melting in subvolcanic plumbing systems. Therefore, ne-normative dykes in arc batholiths may indicate periods with high magma fluxes. Supplementary Information: The online version contains supplementary material available at 10.1007/s00410-023-02047-3.

Discriminant analysis of amphiboles: Additional considerations.

Amphibole minerals are found throughout nature and could pose a respiratory hazard if these exist in the asbestiform growth habit. Though amphibole asbestos has not been used in commercial products as an added material for more than 30 years, these minerals could exist in other materials as trace contaminants as well as occurring in mines and earth-moving environments. It is necessary, then, that the asbestiform amphibole minerals be properly identified in order to appropriately use health-protective measures. Recent analyses of various amphibole data sets have been used to derive a discriminant function that can be used to differentiate asbestiform amphibole from non-asbestiform amphibole minerals. This paper expands on this function and examines the validity of the procedure for different size fractions of minerals. This analysis suggests that the derived function is appropriate for fibers 10 µm and longer. For fibers shorter than 10 µm, the data suggest that a broader acceptance limit may be needed. The data also suggest that current analytical procedures may require some adjustment to provide more accurate details on the widths of fibers. With additional samples, the accuracy of the discriminate function can be improved by calculating functions for each mineral.

Quantitative assessment of mesothelioma and lung cancer risk based on Phase Contrast Microscopy (PCM) estimates of fibre exposure: an update of 2000 asbestos cohort data.

An earlier meta-analysis of mortality studies of asbestos-exposed worker populations, quantified excess mesothelioma and lung cancer risks in relation to cumulative exposure to the three main commercial asbestos types. The aim of this paper was to update these analyses incorporating new data based on increased follow-up of studies previously included, as well as studies of worker populations exposed predominantly to single fibre types published since the original analysis. Mesothelioma as a percentage of expected mortality due to all causes of death, percentage excess lung cancer and mean cumulative exposure were abstracted from available mortality studies of workers exposed predominantly to single asbestos types. Average excess mesothelioma and lung cancer per unit of cumulative exposure were summarised for groupings of studies by fibre type; models for pleural and peritoneal mesothelioma risk and lung cancer risk in terms of cumulative exposure for the different fibre types were fitted using Poisson regression. The average mesothelioma risks (per cent of total expected mortality) per unit cumulative exposure (f/cc.yr), RM, were 0.51 for crocidolite, 0.12 for amosite, and 0.03 for the Libby mixed amphiboles cohort. Significant heterogeneity was present for cohorts classed as chrysotile, with RM values of 0.01 for chrysotile textiles cohorts and 0.0011 for other chrysotile-exposed cohorts. Average percentage excess lung cancer risks per unit cumulative exposure, RL, were 4.3 for crocidolite and amosite combined, 0.82 for Libby. Very significant heterogeneity was present for chrysotile-exposed cohorts with RL values spanning two orders of magnitude from 0.053 for the Balangero mine to 4.8 for the South Carolina textiles cohort. Best fitting models suggest a non-linear exposure-response in which the peritoneal mesothelioma risk is proportional to approximately the square of cumulative exposure. Pleural mesothelioma and lung cancer risk were proportion to powers of cumulative exposure slightly less than one and slightly higher than one respectively.

Characterization of elongate mineral particles including talc, amphiboles, and biopyriboles observed in mineral derived powders: Comparisons of analysis of the same talcum powder samples by two laboratories.

Elongate mineral particles, including asbestos, have long been screened in talc and other mineral powders. In recent years, there has been a renewed scrutiny of talc containing asbestos due to allegations in civil litigation in the United States as well as reports, proposals, and white papers by international laboratories and government bodies related to this subject. This study demonstrates the importance of the fundamental understanding of both mineralogy and its application, using microscopy with empirical examples from conflicting analyses of the same talc powders by two independent laboratories in civil litigation in the United States. Methods include polarized light microscopy (PLM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) in the accurate measurement of morphological, optical, compositional, and structural data to characterize mineral-based samples. Discussions in this study include: 1) contrasting the interlaboratory findings of amphibole and amphibole asbestos by PLM and TEM using various preparation techniques, 2) the use of multiple analytical tools on a singular particle for identification, 3) the misidentification of anthophyllite asbestos by inexpert use of electron diffraction using TEM, and 4) the misidentification of chrysotile in talc by PLM. These examples emphasize the importance of not only maintaining the existing requirements, but of the need for even more rigorous analytical requirements in routine monitoring of elongate mineral particles that may occur in mineral-based powders.

Nucleation of naturally occurring calcic amphibole asbestos.

This article proposes an initial model of natural asbestiform minerals growing in four stages. Structures dating from the early stages of the development were observed in the damaged zone surrounding meso-fractures, more particularly in microfractures, microcavities and microcracks that lie in front of and along mesofractures. This study is limited to calcium amphiboles cross-fibers, which develop from altered calcium amphiboles. The observations were made using PLM, with some using TEM. The samples are amphibolites, dolerites and skarns from France. All these rocks have in common that they have been exposed to hydrothermal circulation which gives them a propylite character. The earliest phenomenon was the development of metasomatic veins. In these veins, actinolite form pseudomorphs after hornblendes. The new amphiboles preserve the original morphology of hornblende, in particular the appearance of the cleavages. In the second stage, hydrothermal Fluid circulation promotes the development of subgrains (DSG) with boundaries generally parallel to the cleavage. Some sub-grains become thinner and more and more individualized due to dissolution by the hydrothermal fluid. The third stage is fracturing. The irregular ends of DSGs and amphibole debris can form the substrate of asbestiform mineral nuclei. Further dissolution of DSGs can also lead to the creation of substrates. The last stage is the nucleation and growth. The nuclei have a conical shape and variable widths, from a few microns to about ten microns. The basal parts of the asbestos minerals (BPAMs) extend the DSGs along the c axis. BPAMs have variable widths and can divide during their development at the level of transverse microcracks. BPAMs when not dividing have a morphology comparable to that of whisker nanocrystals synthesized using the vapor-liquid-crystal mechanism. The shape of the fragments from BPMAs is close to that of DSGs as both have variable widths and both have lengths controlled by microcracks.

Asbestiform fibers and cleavage Fragments: Conceptual approaches for differentiation in laboratory practice and data analysis.

The respirable fractions from 46 different crushed amphibole samples were separated by water elutriation. The dimensions of approximately 200 elongate mineral particles (EMPs) longer than 5 µm in each of these fractions were measured by transmission electron microscopy (TEM). The data were used to address three questions: 1. Can amphiboles be classified on a scale that represents the level of inhalation hazard they present? 2. Can prismatic amphibole be discriminated from amphibole asbestos on the basis of EMP size distributions and concentration measurements? 3. How do different exposure indices (Phase Contrast Microscopy Equivalent (PCME), Berman & Crump protocol fibers, Chatfield extra-criteria EMPs) compare when applied to these amphibole samples? For each sample, the number of respirable EMPs longer than 5 µm per gram of respirable dust and the number of extra-criteria EMPs per gram of respirable dust were calculated. The number of respirable EMPs longer than 5 µm per gram of respirable dust and the proportion of those with dimensions associated with mesothelioma in animal studies were considered to be contributors to the inhalation hazard presented by amphibole dust. In addition to these concentration measurements, the median EMP width, median aspect ratio and the aspect ratio geometric standard deviation (GSD) were considered to be relevant parameters in discriminating prismatic amphibole from asbestiform amphibole. A plot of the aspect ratio GSD against either the concentration of respirable EMPs per gram of respirable dust, the median aspect ratio or the median width allowed discrimination. The data showed a close correspondence between exposures in terms of Chatfield extra-criteria EMPs and Berman and Crump protocol structures for all of the amphibole samples. However, although for commercial asbestos varieties exposures in terms of PCME fibers were comparable to those of the other two metrics, they greatly exceeded those for non-asbestiform amphiboles.

Natural mineral fibers: conducting inhalation toxicology studies-part B: development of a nose-only exposure system for repeat-exposure in vivo study of Libby amphibole aerosol.

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.

Natural mineral fibers: conducting inhalation toxicology studies - part A: Libby Amphibole aerosol generation and characterization method development.

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.

The health effects of short fiber chrysotile and amphibole asbestos.

The potential toxic effects of short chrysotile and amphibole asbestos fibers with lengths <5 to ∼10 µm have been debated over the years. This stems from the large database of epidemiology, toxicology, and in-vitro studies, each of which often provides different information in understanding and differentiating the effects of short fibers. The epidemiology studies in which the cancer potency estimates were based upon relatively high exposure concentrations provide a conservative assessment that shorter fibers would have little if any effect, especially under controlled exposure or environmental conditions that may occur today. The QSAR models have shown that fiber aspect ratio and Mg content are excellent predictors of cancer potency and that short fibers/particles of amphibole would have no effect. The studies of motor vehicle mechanics and in particular workers who serviced chrysotile containing brakes with the majority of the fibers being short provides evidence that motor vehicle mechanics, including workers who were engaged in brake repair, are not at an increased risk of mesothelioma. Several inhalation toxicology studies clearly differentiated that short chrysotile and amphibole asbestos fibers did not produce a significant carcinogenic effect in the lung or pleural cavity. Because of dosing and lack of sensitivity to biosolubility, in vitro studies can be difficult to interpret; however, a number have differentiated short chrysotile and amphibole asbestos fibers from long fibers. Integral to understanding the importance of fiber length in determining possible health effects is an understanding of the biological and physiological function of the respiratory system. Short asbestos fibers, like innocuous dust, can be cleared through the tracheobronchial ciliated mucous transport, phagocytized by macrophages and cleared via the bronchial tree, and can also be removed through the lymphatic system. While the first two methods can remove them from the lung, with lymphatic transport through one-way valves, fibers are removed from the active area of the lung where the fiber-related disease has been shown to develop and can accumulate in lymphatic sumps and lymph nodes. While short asbestos fibers are present in most occupational or environmental exposures, the large body of studies strongly supports that they do not contribute to the health effects of asbestos exposure.

Case-fatality study of workers and residents with radiographic asbestos disease in Libby, Montana.

BACKGROUND: Vermiculite ore from Libby, Montana contains on average 24% of a mixture of toxic and carcinogenic amphibole asbestiform fibers. These comprise primarily winchite (84%), with smaller quantities of richterite (11%) and tremolite (6%), which are together referred to as Libby amphibole (LA). METHODS: A total of 1883 individuals who were occupationally and/or environmentally exposed to LA and were diagnosed with asbestos-related pleuropulmonary disease (ARPPD) following participation in communitywide screening programs supported by the Agency for Toxic Substances and Disease Registry (ATSDR) and followed up at the Center for Asbestos Related Disease (CARD) between 2000 and 2010. There were 203 deaths of patients with sufficient records and radiographs. Best clinical and radiologic evidence was used to determine the cause of death, which was compared with death certificates. RESULTS: Asbestos-related mortality was 55% (n = 112) in this series of 203 patients. Of the 203 deaths, 34 (17%) were from asbestos-related malignancy, 75 (37%) were from parenchymal asbestosis, often with pleural fibrosis, and 3 (1.5%) were from respiratory failure secondary to pleural thickening. CONCLUSIONS: Asbestos is the leading cause of mortality following both occupational and nonoccupational exposure to LA in those with asbestos-related disease.

Final results from a 90-day quantitative inhalation toxicology study evaluating the dose-response and fate in the lung and pleura of chrysotile-containing brake dust compared to TiO2, chrysotile, crocidolite or amosite asbestos: Histopathological examination, confocal microscopy and collagen quantification of the lung and pleural cavity.

The final results from this multi-dose, 90-day inhalation toxicology study in the rat with life-time post-exposure observation have shown a significant fundamental difference in pathological response and tumorgenicity between brake dust generated from brake pads manufactured with chrysotile or from chrysotile alone in comparison to the amphiboles, crocidolite and amosite asbestos. The groups exposed to brake dust showed no significant pathological or tumorigenic response in the respiratory track compared to the air control group at exposure concentrations and deposited doses well above those at which humans have been exposed. Slight alveolar/interstitial macrophage accumulation of particles was noted. Wagner grades were 1-2 (1 = control group), similar to the TiO2 particle control group. Chrysotile was not biopersistent, exhibiting in the lung a deterioration of its matrix which results in breakage into particles and short fibers which can be cleared by alveolar macrophages and which can continue to dissolve. Particle-laden macrophage accumulation was observed, leading to a very-slight interstitial inflammatory response (Wagner grade 1-3). There was no peribronchiolar inflammation, occasional very-slight interstitial fibrosis (Wagner grade 4), and no exposure-related tumorigenic response. The pathological response of crocidolite and amosite compared to the brake dust and chrysotile was clearly differentiated by the histopathology and the confocal analysis. Crocidolite and amosite induced persistent inflammation, microgranulomas, persistent fibrosis (Wagner grades 4), and a dose-related lung tumor response. Confocal microscopy quantified extensive inflammatory response and collagen development in the lung, visceral and parietal pleura as well as pleural adhesions. These results provide a clear foundation for differentiating the innocuous effects of brake dust exposure from the adverse effects following amphibole asbestos exposure.

Discrepancies of asbestos body and fiber content between formalin-fixed and corresponding paraffin embedded lung tissue.

BACKGROUND: Formalin-fixed lung tissue and paraffin blocks containing peripheral lung tissue obtained from subjects with an occupational asbestos exposure are both regarded to be suitable to determine asbestos load. Because sample preparation of paraffin blocks requires a more intense treatment than formalin-fixed tissue, we tested whether asbestos analysis of formalin-fixed lung tissue and paraffin blocks obtained from the same patients deliver comparable results. MATERIALS AND METHODS: We determined numbers of asbestos bodies (AB) and amphibole asbestos fibers (AF) in formalin-fixed lung tissue and corresponding paraffin blocks from 36 patients. For AB counts, samples were digested in sodium hypochlorite. For AF analysis, tissue was freeze-dried and then ashed. Results were reported as numbers of AB and AF per gram dry lung tissue. RESULTS: Both AB counts as well as AF counts were lower in paraffin blocks than formalin-fixed lung tissue. Compared to formalin-fixed tissue, the limit of detection was higher for paraffin blocks, rendering more results from paraffin blocks not interpretable than from formalin-fixed tissue (8 samples versus 1 for AB and 15 samples versus 4 for AF). DISCUSSION AND CONCLUSION: Asbestos analysis of paraffin blocks may lead to underestimation of asbestos exposure. This should be considered when assessing occupational asbestos exposure through lung dust analysis in medico-legal evaluation.

Late Inflammation Induced by Asbestiform Fibers in Mice Is Ameliorated by a Small Molecule Synthetic Lignan.

Exposure to Libby amphibole (LA) asbestos-like fibers is associated with increased risk of asbestosis, mesothelioma, pulmonary disease, and systemic autoimmune disease. LGM2605 is a small molecule antioxidant and free radical scavenger, with anti-inflammatory effects in various disease models. The current study aimed to determine whether the protective effects of LGM2605 persist during the late inflammatory phase post-LA exposure. Male and female C57BL/6 mice were administered daily LGM2605 (100 mg/kg) via gel cups for 3 days before and 14 days after a 200 µg LA given via intraperitoneal (i.p.) injection. Control mice were given unsupplemented gel cups and an equivalent dose of i.p. saline. On day 14 post-LA treatment, peritoneal lavage was assessed for immune cell influx, cytokine concentrations, oxidative stress biomarkers, and immunoglobulins. During the late inflammatory phase post-LA exposure, we noted an alteration in trafficking of both innate and adaptive immune cells, increased pro-inflammatory cytokine concentrations, induction of immunoglobulin isotype switching, and increased oxidized guanine species. LGM2605 countered these changes similarly among male and female mice, ameliorating late inflammation and altering immune responses in late post-LA exposure. These data support possible efficacy of LGM2605 in the prolonged treatment of LA-associated disease and other inflammatory conditions.

Modeling mesothelioma risk factors from amphibole fiber dimensionality: mineralogical and epidemiological perspective.

Amphiboles are common rock-forming minerals but when they form asbestos, they are known carcinogens. Mesothelioma mortality among miners and millers per the unit of asbestiform amphibole exposure varies significantly across cohorts when asbestos exposure measurements are based on the membrane filter method. Because the cohorts were exposed to different occurrences of asbestiform amphibole, variance in mesothelioma potency (RM ) among cohorts is likely due to differences in exposure characteristics not reflected by the membrane filter method. In this paper using both linear and nonlinear models we correlate RM from four mining and milling cohorts with two-dimensional parameters of the exposure. The parameters are based on the proportion of elongated minerals that are >5 µm in length from each occurrence that also have either (a) width ≤ 0.15 µm, or (b) width ≤ 0.25 µm. Based on the models we derived, it was possible to quantify RM for the occurrences of asbestiform amphibole associated with mesothelioma excess but for which epidemiologically based RM has not been published. It was demonstrated that modeled RM for amphibole occurrences in nonasbestiform habits are lower (fibrous glaucophane) or not significant (cleavage fragments). The results of the study can be used in a risk assessment of elongated mineral particles and have implications for public policy and regulations.

Synthetic secoisolariciresinol diglucoside (LGM2605) inhibits Libby amphibole fiber-induced acute inflammation in mice.

BACKGROUND: Exposure to the Libby amphibole (LA) asbestos-like fibers found in Libby, Montana, is associated with inflammatory responses in mice and humans, and an increased risk of developing mesothelioma, asbestosis, pleural disease, and systemic autoimmune disease. Flaxseed-derived secoisolariciresinol diglucoside (SDG) has anti-inflammatory, anti-fibrotic, and antioxidant properties. We have previously identified potent protective properties of SDG against crocidolite asbestos exposure modeled in mice. The current studies aimed to extend those findings by evaluating the immunomodulatory effects of synthetic SDG (LGM2605) on LA-exposed mice. METHODS: Male and female C57BL/6 mice were given LGM2605 via gavage initiated 3 days prior to and continued for 3 days after a single intraperitoneal dose of LA fibers (200 µg) and evaluated on day 3 for inflammatory cell influx in the peritoneal cavity using flow cytometry. RESULTS: LA exposure induced a significant increase (p < 0.0001) in spleen weight and peritoneal influx of white blood cells, all of which were reduced with LGM2605 with similar trends among males and females. Levels of peritoneal PMN cells were significantly (p < 0.0001) elevated post LA exposure, and were significantly (p < 0.0001) blunted by LGM2605. Importantly, LGM2605 significantly ameliorated the LA-induced mobilization of peritoneal B1a B cells. CONCLUSIONS: LGM2605 reduced LA-induced acute inflammation and WBC trafficking supporting its possible use in mitigating downstream LA fiber-associated diseases. SUMMARY: Following acute exposure to Libby amphibole (LA) asbestos-like fibers, synthetic SDG (LGM2605), a small synthetic molecule, significantly reduced the LA-induced increase in spleen weight and peritoneal inflammation in C57BL/6 male and female mice. Our findings highlight that LGM2605 has immunomodulatory properties and may, thus, likely be a chemopreventive agent for LA-induced diseases.

Identifying the ingredients of hydrous arc magmas: insights from Mt Lamington, Papua New Guinea.

Volcanism is the surface expression of magma intrusion, crystallization, assimilation and hybridization processes operating throughout the crust over a range of time periods. Many magmas, including those erupted at subduction zones, have complex textures that reflect these processes. Here, we use textural and geochemical characteristics of calcic amphiboles to help identify multiple ingredients of subduction zone magmatism at Mt Lamington volcano, Papua New Guinea. Our approach uses existing trace element partitioning schemes to calculate the compositions of amphibole equilibrium melts (AEMs). The AEM compositions show that Mt Lamington andesites and plutonic enclaves are dominated by fractionation of amphibole + plagioclase + biotite, with assimilation of plagioclase and zircon. Magnesiohastingsite crystals in the andesite and diktytaxitic mafic enclaves reflect multiple episodes of recharge by more primitive, geochemically variable melts. The andesite also contains clots with rounded grains and melt on grain boundaries. These features indicate slow crystallization, and the retention of melt films could significantly enhance the potential for remobilization of crystals by infiltrating melts or during magma mixing. Variations in crystallization conditions could thus significantly affect the mush microstructure. We suggest that this could result in a significant bias of the volcanic record towards the preferential incorporation of more slowly cooled plutonic material from the lower crust or from more thermally mature plumbing systems. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.