3D-printed bredigite scaffolds with ordered arrangement structures promote bone regeneration by inducing macrophage polarization in onlay grafts.

Bone tissue engineering scaffolds may provide a potential strategy for onlay bone grafts for oral implants. For determining the fate of scaffold biomaterials and osteogenesis effects, the host immune response is crucial. In the present study, bredigite (BRT) bioceramic scaffolds with an ordered arrangement structure (BRT-O) and a random morphology (BRT-R) were fabricated. The physicochemical properties of scaffolds were first characterized by scanning electron microscopy, mechanical test and micro-Fourier transform infrared spectroscopy. In addition, their osteogenic and immunomodulatory properties in an onlay grafting model were investigated. In vitro, the BRT-O scaffolds facilitated the macrophage polarization towards a pro-regenerative M2 phenotype, which subsequently facilitated the migration and osteogenic differentiation of bone marrow-derived mesenchymal stem cells. In vivo, an onlay grafting model was successfully established in the cranium of rabbits. In addition, the BRT-O scaffolds grafted on rabbit cranium promoted bone regeneration and CD68 + CD206 + M2 macrophage polarization. In conclusion, the 3D-printed BRT-O scaffold presents as a promising scaffold biomaterial for onlay grafts by regulating the local immune microenvironment.

Elongated particulate burden in an individual who died of mesothelioma and had an occupational history as a talc "mucker".

INTRODUCTION: Tissue from a 77-year-old man diagnosed with mesothelioma was referred with a request for identification of the presence of fibrous structures in tissue samples. The individual's work history including working as a "mucker" at a specific "industrial" talc mine. METHODS: Ferruginous bodies in the tissue digests as well as asbestos fibers were found. A bulk sample of a talc containing product from that mine was also analyzed. DISCUSSIONS/CONCLUSIONS: The correlation between the unique asbestos mineral/fibrous content of the talc to which he was exposed and findings of the same type of asbestos found in his lung is discussed. The type of asbestos found (tremolite) is a "non-commercial" type of asbestos that has been identified in some talc deposits. Tremolite, like all forms of asbestos is a causative agent for mesothelioma-the disease from which this individual suffered.

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.

Environmental asbestos exposure from nephrite jade mining and lung cancer.

BACKGROUND: Nephrite is an asbestos mineral composed of tremolite and actinolite. Fengtian is a community where nephrite was mined between 1970 and 1980 and asbestos was mined between 1960 and 1985. The lung cancer risk to the surrounding community is unknown. AIMS: To analyse the trend of lung cancer caused by environmental contamination from nephrite mining. METHODS: We conducted a field survey of nephrite mines and tracked new cases of lung cancer from 1980 to 2019. We calculated the age-standardized incidence rates (ASIRs) and applied join-point regression to examine the lung cancer trend. We assessed the age effect, period effect, and birth cohort effect on lung cancer risk. RESULTS: The nephrite mines were contaminated with chrysotile and tremolite/actinolite asbestos. A total of 278 new cases of lung cancer were reported during the study period. There was an apparent age effect and a slight period effect for lung cancer. After adjustment for the age and period effects, the birth cohort born between 1970 and 1980 during the period of nephrite mass production had the highest relative risk compared with other birth cohorts. The ASIR of lung cancer increased significantly from 1980 to 2010 (the annual percentage change = 6.8 %, 95 % CI: 4.0-9.7 %, P < 0.01) and then decreased 30 years after the cessation of nephrite jade mining. CONCLUSION: Nephrite mining increases the risk of lung cancer in nearby communities.

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.

Geological and mineralogical characterization of fibrous tremolite from Iacolinei quarry (Basilicata, Italy).

Naturally Occurring Asbestos (NOA) has drawn the attention worldwide when investigation revealed an increased incidence of malignant mesothelioma in population living near NOA sites. In Basilicata region (South Italy), population living in the villages of Castelluccio Superiore and Inferiore, Lauria, Latronico, Episcopia, San Severino Lucano, and Francavilla in Sinni may be considered at high risk of asbestos exposure because these villages are either surrounded by or built on NOA-rich ophiolitic outcrops. In this work we investigated an asbestos tremolite sample coming from the ophiolitic rocks outcropping in the quarry of Iacolinei, widely used in the past to extract aggregates for various applications.  A detailed mineralogical characterization has been attained by using a multi-analytical approach (EMPA, SEM-EDS, TEM-EDS, Mössbauer, µ-Raman, X-ray powder diffraction, and thermal analysis). Morphological investigation highlighted that the sample is composed of long fibers (> 5 µm) with a significant fraction (ca. 55%) having width below 0.25 µm, considered the most biologically active fibers. Moreover, the crystal chemical characterization showed that Fe occurs at the octahedral sites of the tremolite structure. It should be noted that Fe plays a primary role in the toxicity of asbestos. Based on these results, the investigated asbestos tremolite may be considered a potent mesothelial carcinogen, requiring therefore special attention for public health protection purposes. Investigations using sentinel animals to assess the diffusion of the tremolite fibers into the environment from the serpentinite rocks and soils of Iacolinei quarry are in progress.

An updated evaluation of reported no-observed adverse effect levels for chrysotile, amosite, and crocidolite asbestos for lung cancer and mesothelioma.

This analysis updates two previous analyses that evaluated the exposure-response relationships for lung cancer and mesothelioma in chrysotile-exposed cohorts. We reviewed recently published studies, as well as updated information from previous studies. Based on the 16 studies considered for chrysotile (<10% amphibole), we identified the "no-observed adverse effect level" (NOAEL) for lung cancer and/or mesothelioma; it should be noted that smoking or previous or concurrent occupational exposure to amphiboles (if it existed) was not controlled for. NOAEL values ranged from 2.3-<11.5 f/cc-years to 1600-3200 f/cc-years for lung cancer and from 100-<400 f/cc-years to 800-1599 f/cc-years for mesothelioma. The range of best-estimate NOAELs was estimated to be 97-175 f/cc-years for lung cancer and 250-379 f/cc-years for mesothelioma. None of the six cohorts of cement or friction product manufacturing workers exhibited an increased risk at any exposure level, while all but one of the six studies of textile workers reported an increased risk at one or more exposure levels. This is likely because friction and cement workers were exposed to much shorter chrysotile fibers. Only eight cases of peritoneal mesothelioma were reported in all studies on predominantly chrysotile-exposed cohorts combined. This analysis also proposed best-estimate amosite and crocidolite NOAELs for mesothelioma derived by the application of relative potency estimates to the best-estimate chrysotile NOAELs for mesothelioma and validated by epidemiology studies with exposure-response information. The best-estimate amosite and crocidolite NOAELs for mesothelioma were 2-5 f/cc-years and 0.6-1 f/cc-years, respectively. The rate of peritoneal mesothelioma in amosite- and crocidolite-exposed cohorts was between approximately 70- to 100-fold and several-hundred-fold higher than in chrysotile-exposed cohorts, respectively. These findings will help characterize potential worker and consumer health risks associated with historical and current chrysotile, amosite, and crocidolite exposures.

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.

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.

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.

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.

An updated review of diffuse mesothelioma of the pleura - A sentinel health event of potential elongate mineral particle pathogenicity.

There are approximately 400 inorganic minerals in the Earth's crust, some of which can be encountered as elongate mineral particles [EMPs] with dimensional characteristics similar to the six minerals known as asbestos and other asbestiform amphiboles with established human pathogenicity. In addition, the rapidly developing field of nanotechnology is producing an ever-increasing array of high aspect ratio engineered nanomaterials [HARNs] with physical dimensions and biodurability similar to the asbestos fiber types with recognized pathogenic potential. Many of these non-asbestos/non-asbestiform EMPs and HARNs with the potential for aerosolization into the breathing zones of workers and in individuals in non-occupational environments have not yet been thoroughly studied with respect to their potential human pathogenicity, a fact which obviously poses concerns for both occupational health and public health professionals. On the basis of dose-response considerations it seems reasonable to infer that if any of these non-regulated EMPs or HARNs actually are pathogenic, then those mineral fiber exposure-induced disorders associated with the lowest cumulative exposure doses of the commercial amphibole types of asbestos, that is, diffuse mesothelioma of the pleura, and its non-malignant correlate of benign parietal pleural plaques, are those which are most likely to occur following inhalational exposures to any of the non-regulated EMPs and HARNs. Because of that observation, this paper reviews certain aspects of diffuse mesothelioma, including a summary of recent changes in the nomenclature of diffuse mesothelioma of the pleura; of both the descriptive and the analytical epidemiology of the disease; of the etiologies of mesothelioma, both "exposure" related and endogenous in nature; and of the asbestos population attributable fraction for diffuse mesotheliomas in the USA, both historically and in the future.

Mechanisms and shapes of causal exposure-response functions for asbestos in mesotheliomas and lung cancers.

This paper summarizes recent insights into causal biological mechanisms underlying the carcinogenicity of asbestos. It addresses their implications for the shapes of exposure-response curves and considers recent epidemiologic trends in malignant mesotheliomas (MMs) and lung fiber burden studies. Since the commercial amphiboles crocidolite and amosite pose the highest risk of MMs and contain high levels of iron, endogenous and exogenous pathways of iron injury and repair are discussed. Some practical implications of recent developments are that: (1) Asbestos-cancer exposure-response relationships should be expected to have non-zero background rates; (2) Evidence from inflammation biology and other sources suggests that there are exposure concentration thresholds below which exposures do not increase inflammasome-mediated inflammation or resulting inflammation-mediated cancer risks above background risk rates; and (3) The size of the suggested exposure concentration threshold depends on both the detailed time patterns of exposure on a time scale of hours to days and also on the composition of asbestos fibers in terms of their physiochemical properties. These conclusions are supported by complementary strands of evidence including biomathematical modeling, cell biology and biochemistry of asbestos-cell interactions in vitro and in vivo, lung fiber burden analyses and epidemiology showing trends in human exposures and MM rates.

Dimensions of elongate mineral particles and cancer: A review.

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.

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.

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.

Lung asbestos fiber burden analysis: effects of the counting rules for legal medicine evaluations.

OBJECTIVES: The work shows the effect of counting rules, such as analysis magnification and asbestos fiber dimension to be count (with length ≥5 µm or also asbestos fibers with length <5 µm) in the lung asbestos fiber burden analysis for legal medicine evaluations. METHODS: On the same lung tissue samples, two different analyses were carried out to count any asbestos fibers with length ≥1 µm and with length ≥5 µm. Results of the amphibole burden of the two analyses were compared by linear regression analysis on log10-transformed values. RESULTS: The analysis should be carried out at an appropriate magnification and on samples prepared in such a way as they allow the counting of very fine fibers. If the analysis is limited to the asbestos fibers with length ≥5 µm, there is a high risk of not detecting possible residual chrysotile fiber burden and thinner crocidolite asbestos fibers. CONCLUSIONS: On average we estimated that 1 amphibole fiber with length ≥5 µm corresponds to ∼8 amphibole fibers with length ≥1 µm in the lung. The values of the Helsinki criteria should be updated taking this into account.

Toxicological and epidemiological approaches to carcinogenic potency modeling for mixed mineral fiber exposure: the case of fibrous balangeroite and chrysotile.

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.

Manufactured doubt and the EPA 2020 chrysotile asbestos risk assessment.

While all forms of asbestos have been determined to be carcinogenic to humans by the International Agency for Research on Cancer (IARC) as well as other authoritative bodies, the relative carcinogenic potency of chrysotile continues to be argued, largely in the context of toxic tort litigation. Relatively few epidemiologic studies have investigated only a single form of asbestos; however, one study that included an asbestos textile plant located in Marshville, North Carolina that processed chrysotile asbestos was used by the United States Environmental Protection Agency (EPA) in 2020 to help inform the agency's chrysotile asbestos risk assessment. During the EPA proceedings toxic tort defense consultants submitted comments to the EPA docket and made public presentations asserting that the Marshville plant had processed amphibole asbestos types and should not be used for the chrysotile risk assessment. A detailed evaluation of defense consultant assertions and supporting information and a full assessment of the available information concerning asbestos types used at the Marshville plant was undertaken. The preponderance of evidence continues to support the conclusion that neither amosite nor crocidolite were likely to have been processed in the Marshville textile plant. Defense consultants' assertions about chrysotile use are not supported by the preponderance of evidence and constitute an example of manipulation of information to cast uncertainty and doubt rather than to seek truth and contribute to the body of scientific evidence.