AFM1 exposure in male balb/c mice and intervention strategies against its immuno-physiological toxicity using clay mineral and lactic acid bacteria alone or in combination.

CONTEXT: Aflatoxins are the most harmful mycotoxins that cause human and animal health concerns. Aflatoxin M1 (AFM1) is the primary hydroxylated metabolite of aflatoxin B1 and is linked to the development of hepatocellular carcinoma and immunotoxicity in humans and animals. Because of the important role of dairy products in human life, especially children, AFM1 is such a major concern to humans because of its frequent occurrence in dairy products at concentrations high enough to cause adverse effects to human and animal health. Reduced its bioavailability becomes a high priority in order to protect human and animal health. OBJECTIVES: This study aimed to investigate, in vivo, the ability of lactic acid bacteria (lactobacillus rhamnosus GAF01, LR) and clay mineral (bentonite, BT) mixture to mitigate/reduce AFM1-induced immunotoxicity, hepatotoxicity, nephrotoxicity and oxidative stress in exposed Balb/c mice. MATERIALS AND METHODS: The in vivo study was conducted using male Balb/c mice that treated, orally, by AFM1 alone or in combination with LR and/or BT, daily for 10 days as follows: group 1 control received 200 µl of PBS, group 2 treated with LR alone (2.108 CFU/mL), group 3 treated with BT alone (1 g/kg bw), group 4 treated with AFM1 alone (100 µg/kg), group 5 co-treated with LR + AFM1, group 6 co-treated with BT + AFM1, group 7 co-treated with BT + LR + AFM1. Forty-eight h after the end of the treatment, the mice were sacrificed and the blood, spleen, thymus, liver and kidney were collected. The blood was used for biochemical and immunological study. Spleen and thymus samples were used to thymocytes and splenocytes assessments. Liver and kidney samples were the target for evaluation of oxidative stress enzymes status and for histological assays. RESULTS: The results showed that AFM1 caused toxicities in male Blab/c mice at different levels. Treatment with AFM1 resulted in severe stress of liver and kidney organs indicated by a significant change in the biochemical and immunological parameters, histopathology as well as a disorder in the profile of oxidative stress enzymes levels. Also, it was demonstrated that AFM1 caused toxicities in thymus and spleen organs. The co-treatment with LR and/or BT significantly improved the hepatic and renal tissues, regulated antioxidant enzyme activities, spleen and thymus viability and biochemical and immunological parameters. LR and BT alone showed to be safe during the treatment. CONCLUSION: In summary, the LR and/or BT was able to reduce the biochemical, histopathological and immunological damages induced by AFM1 and indeed it could be exploited as one of the biological strategies for food and feedstuffs detoxification.

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.

Cytotoxicity of fibrous antigorite from New Caledonia.

Exposure to asbestos and asbestos-like minerals has been related to the development of severe lung diseases, including cancer and malignant mesothelioma (MM). A high incidence of non-occupational MM was observed in New Caledonia (France) in people living in proximity of serpentinite outcrops, containing chrysotile and fibrous antigorite. Antigorite is a magnesium silicate, which shares with chrysotile asbestos the chemical formula. To achieve information on antigorite toxicity, we investigated the physico-minero-chemical features relevant for toxicity and cellular effects elicited on murine macrophages (MH-S) and alveolar epithelial cells (A549) of three fibrous antigorites (f-Atg) collected in a Caledonian nickel lateritic ore and subjected to supergene alteration. Field Atg were milled to obtain samples suitable for toxicological studies with a similar particle size distribution. UICC chrysotile (Ctl) and a non-fibrous antigorite (nf-Atg) were used as reference minerals. A high variability in toxicity was observed depending on shape, chemical alteration, and surface reactivity. The antigorites shared with Ctl a similar surface area (16.3, 12.1, 20.3, 13.4, and 15.6 m2/g for f-Atg1, 2, 3, nf-Atg, and Ctl). f-Atg showed different level of pedogenetic weathering (Ni depletion f-Atg1 ≪ f-Atg2 and 3) and contained about 50% of elongated mineral particles, some of which exhibited high aspect ratios (AR > 10 µm, 20%, 26%, 31% for f-Atg1, 2, and 3, respectively). The minerals differed in bio-accessible iron at pH 4.5 (f-Atg1 ≪ f-Atg3, < f-Atg2, nf-Atg < Ctl), and surface reactivity (ROS release in solution, f-Atg1 ≪ f-Atg2, 3, nf-Atg, and Ctl). f-Atg2 and f-Atg3 induced oxidative stress and pro-inflammatory responses, while the less altered, poorly reactive sample (f-Atg1) induced negligible effects, as well nf-Atg. The slow dissolution kinetics observed in simulated body fluids may signal a high biopersistence. Overall, our work revealed a significative cellular toxicity of f-Atg that correlates with fibrous habit and surface reactivity.

Excitable systems: A new perspective on the cellular impact of elongate mineral particles.

We investigate how the geometry of elongate mineral particles (EMPs) in contact with cells influences esotaxis, a recently discovered mechanism of texture sensing. Esotaxis is based on cytoskeletal waves and oscillations that are nucleated, shaped, and steered by the texture of the surroundings. We find that all EMPs studied trigger an esotactic response in macrophages, and that this response dominates cytoskeletal activity in these immune cells. In contrast, epithelial cells show little to no esotactic response to the EMPs. These results are consistent with the distinct interactions of both cell types with ridged nanotopographies of dimensions comparable to those of asbestiform EMPs. Our findings raise the question of whether narrow, asbestiform EMPs may also dominate cytoskeletal activity in other types of immune cells that exhibit similar esotactic effects. These findings, together with prior studies of esotaxis, lead us to the hypothesis that asbestiform EMPs suppress the migration of immune cells and activate immune signaling, thereby outcompeting signals that would normally stimulate the immune system in nearby tissue.

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.

The importance of mineralogical composition for the cytotoxic and pro-inflammatory effects of mineral dust.

BACKGROUND: Respirable mineral particles represent a potential health hazard in occupational settings and ambient air. Previous studies show that mineral particles may induce cytotoxicity and inflammatory reactions in vitro and in vivo and that the potency varies between samples of different composition. However, the reason for these differences is largely unknown and the impact of mineralogical composition on the biological effects of mineral dust remains to be determined. METHODS: We have assessed the cytotoxic and pro-inflammatory effects of ten mineral particle samples of different composition in human bronchial epithelial cells (HBEC3-KT) and THP-1-derived macrophages, as well as their membranolytic properties in erythrocytes. Moreover, the results were compiled with the results of recently published experiments on the effects of stone particle exposure and analysed using linear regression models to elucidate which mineral components contribute most to the toxicity of mineral dust. RESULTS: While all mineral particle samples were more cytotoxic to HBEC3-KT cells than THP-1 macrophages, biotite and quartz were among the most cytotoxic in both cell models. In HBEC3-KT cells, biotite and quartz also appeared to be the most potent inducers of pro-inflammatory cytokines, while the quartz, Ca-feldspar, Na-feldspar and biotite samples were the most potent in THP-1 macrophages. All particle samples except quartz induced low levels of membranolysis. The regression analyses revealed associations between particle bioactivity and the content of quartz, muscovite, plagioclase, biotite, anorthite, albite, microcline, calcite, chlorite, orthopyroxene, actinolite and epidote, depending on the cell model and endpoint. However, muscovite was the only mineral consistently associated with increased cytotoxicity and cytokine release in both cell models. CONCLUSIONS: The present study provides further evidence that mineral particles may induce cytotoxicity and inflammation in cells of the human airways and that particle samples of different mineralogical composition differ in potency. The results show that quartz, while being among the most potent samples, does not fully predict the toxicity of mineral dust, highlighting the importance of other particle constituents. Moreover, the results indicate that the phyllosilicates muscovite and biotite may be more potent than other minerals assessed in the study, suggesting that this group of sheet-like minerals may warrant further attention.

Dimensional characteristics of the major types of amphibole mineral particles and the implications for carcinogenic risk assessment.

Context: Though some significant advances have been made in recent decades to evaluate the importance of size and morphology (habit) of elongate mineral particles (EMPs), further research is needed to better understand the role of each dimensional metric in determining the levels of cancer potency.Objective: To determine dimensional parameters most relevant for predicting cancer potency of durable elongate particles, specifically amphibole and durable silicate minerals generally.Methods: A database on dimensional and other relevant characteristics of elongate amphibole mineral particles was created, containing particle-by-particle information for 128 099 particles. Integral statistical characteristics on dimensionality of various amphibole types and morphological habits of EMPs were calculated, compared, and correlated with published mesothelioma and lung cancer potency factors.Results: The highest absolute Pearson correlation (r = 0.97, r2 = 0.94, p < 0.05) was achieved between mesothelioma potency (RM) and specific surface area. The highest correlation with adjusted lung cancer potency was found with particle aspect ratio (AR) (r = 0.80, r2 = 0.64, p < 0.05). Cluster analysis demonstrates that fractions of thin fibers (width less than 0.15 and 0.25 µm) also closely relate both to lung cancer and RM. Asbestiform and non-asbestiform populations of amphiboles significantly differ by dimensionality and carcinogenic potency.Conclusions: Dimensional parameters and morphological habits of EMPs are the main drivers for the observable difference in cancer potency among amphibole populations.

Integration of Evidence on Community Cancer Risks from Elongate Mineral Particles in Silver Bay, Minnesota.

The potential for cancer-related risks to community members from ambient exposure to elongate mineral particles (EMPs) in taconite processing has not been formally evaluated. We evaluated 926 ambient air samples including 12,928 EMPs (particle structures with length-to-width ratio ≥3:1) collected over 26 years near a taconite processing facility in Silver Bay, Minnesota. Eighty-two percent of EMPs were ≤3 µm in length and 97% of EMPs had an average aspect ratio <20:1. A total of 935 (7.3%) EMPs had length >5 µm and AR ≥3:1. Average ambient concentration of NIOSH countable amphibole EMPs over all years was 0.000387 EMPs per cubic centimeter (EMP/cm3 ). Of 12,765 nonchrysotile EMPs, the number of amphiboles with length and width dimensions that correlate best with asbestos-related carcinogenicity ranged from four (0.03%) to 13 (0.1%) and the associated ambient amphibole air concentrations ranged from 0.000003 to 0.000007 EMP/cm3 . After 65 years of taconite processing in Silver Bay, evidence of an increased risk of mesothelioma and lung cancer in community members who did not work in the taconite industry is lacking. The absence of an increased risk of asbestos-related cancer in the Silver Bay community is coherent with supporting evidence from epidemiological and toxicological studies, as well as ambient exposure data and lake sediment data collected in Minnesota Iron Range communities. Collectively, the data provide consistent evidence that nonasbestiform amphibole minerals lack the carcinogenic potential exhibited by amphibole asbestos.

No pathogenic responses in rat lung upon exposure to ground granulated blast furnace slag (GGBS).

Objective: Granulated blast furnace slag (GBS) is a by-product of the manufacture of iron by thermochemical reduction in a blast furnace. Blast furnace slag is generated at temperatures above 1500 °C. If the liquid slag is quenched very rapidly with water, a glassy slag is generated (GBS). It is used - after grinding <100 µm - [ground granulated blast furnace slag (GGBS)] for cement and concrete production. A small particulate fraction of GGBS might be accessible to the pulmonary alveoli, where it could settle down and induces physiological inflammatory responses. Within the scope of the 'Registration, Evaluation, Authorization and Restriction of Chemicals' (REACH), GGBS was already tested in rats in an acute toxicity inhalation study, as well as in a dose range finding study as a predecessor study for this study. Both did not show systemic and local toxic effect in rats upon inhalation of high-dose GGBS.Material and methods: In this study, low (4.3 mg/m3), intermediate (9.5 mg/m3), and high-dose (24.9 mg/m3) repetitive exposure of GGBS to rats was tested over a period of 4 weeks with 6 h exposure per day for 5 days per week. Results and conclusion: Even at high doses, GGBS was inactive and did not induce clinically relevant phenotypic changes in rats compared to concomitant controls.Together with both the previous acute toxicity and the dose range finding study in rats, it was shown that the exposure to the tested GGBS was unable to induce any severe pathogenic responses.

Dosimetry of inhaled elongate mineral particles in the respiratory tract: The impact of shape factor.

Inhalation exposure to some types of fibers (e.g., asbestos) is well known to be associated with respiratory diseases and conditions such as pleural plaques, fibrosis, asbestosis, lung cancer, and mesothelioma. In recent years, attention has expanded to other types of elongate mineral particles (EMPs) that may share similar geometry with asbestos fibers but which may differ in mineralogy. Inhalability, dimensions and orientation, and density are major determinants of the aerodynamic behavior for fibers and other EMPs; and the resultant internal dose is recognized as being the critical link between exposure and pathogenesis. Insufficient data are available to fully understand the role of specific physicochemical properties on the potential toxicity across various types of fiber materials. While additional information is required to assess the potential health hazards of EMPs, dosimetry models are currently available to estimate the initially deposited internal dose, which is an essential step in linking airborne exposures to potential health risks. Based on dosimetry model simulations, the inhalability and internal dose of EMPs were found to be greater than that of spherical particles having the same mass or volume. However, the complexity of the dependence of internal dose on EMPs dimensions prevented a straightforward formulation of the deposition-dimension (length or diameter) relationship. Because health outcome is generally related to internal dose, consideration of the factors that influence internal dose is important in assessing the potential health hazards of airborne EMPs.

Predicting EMP hazard: Lessons from studies with inhaled fibrous and non-fibrous nano- and micro-particles.

Inhalation exposure to elongated cleavage fragments occurring at mineral and rock mining and crushing operations raises important questions regarding potential health effects given their resemblance to fibers with known adverse health effects like amphibole asbestos. Thus, a major goal for establishing a toxicity profile for elongate mineral particles (EMPs) is to identify and characterize a suspected hazard and characterize a risk by examining together results of hazard and exposure assessment. This will require not only knowledge about biokinetics of inhaled EMPs but also about underlying mechanisms of effects induced by retained EMPs. In vitro toxicity assays with predictive power for in vivo effects have been established as useful screening tools for toxicological characterization of particulate materials including EMPs. Important determinants of physiological/toxicological mechanisms are physico-chemical and functional properties of inhaled particulate materials. Of the physico-chemical (intrinsic) properties, size, shape and surface characteristics are well known to affect toxicological responses; functional properties include (i) solubility/dissolution rate in physiological fluid simulants in vitro and following inhalation in vivo; (ii) ROS-inducing capacity in vitro and in vivo determined as specific particle surface reactivity; (iii) bioprocessing in vivo. A key parameter for all is the dose and duration of exposure, requiring to establish exposure-dose-response relationships. Examples of studies with fibrous and non-fibrous particles are discussed to illustrate the relevancy of evaluating extrinsic and intrinsic particle properties for predicting in vivo responses of new particulate materials. This will allow hazard and risk ranking/grouping based on a comparison to toxicologically well-characterized positive and negative benchmarks. Future efforts should be directed at developing and validating new approaches using in vitro (non-animal) studies for establishing a complete risk assessment for EMPs. Further comparative in-depth analyses with analytical and ultra-high resolution technology examining bioprocessing events at target organ sites have proven highly successful to identify biotransformations in target cells at near atomic level. In the case of EMPs, such analyses can be essential to separate benign from harmful ones.

Analysis and identification of elongated mineral particles in road coated aggregates.

The issue of Elongated Mineral Particles (EMP) in building materials has been revealed during roadworks in 2013 in France. In fact, road coating aggregates are made of specific rock gravels that can contain Naturally Occurring Asbestos (NOA), which is mainly actinolite. The legislation refers to six regulatory asbestos, that consist in asbestiform habitus of the six minerals. The current technical standard is not adapted for analyzing natural material, as it cannot distinguish the asbestiform fibers and the cleavage fragments fibers. Therefore, the Eichrom Laboratories developed an internal method for analyzing rock gravel and identifying the different kind of EMP. This analytical method is based on an accurate sample preparation and three techniques at different resolutions: a petrological analysis with a stereomicroscope, a mineralogical analysis with a Polarized Light Microscope (PLM) and structural and with a Transmission Electronic Microscope (TEM). This innovative procedure is reinforced by the expertise of geologists, which is not necessary for the manufactured products. Putting the process in a national standard is essential for result homogenization of the asbestos testing laboratories.

OSHA and elongate mineral particles.

The United States Occupational Safety and Health Administration (OSHA) was established to provide guidance to protect workers from hazards in the workplace. After broadly adopting extant health and safety standards, OSHA promulgated an expanded standard for regulation of asbestos. This standard provided for regulation of six named minerals and practices to be followed. Since the initial establishment of asbestos regulation by OSHA, other elongate particles have been considered for evaluation. This discussion describes the evolution of the OSHA regulations for asbestos, what they cover and how other materials might be regulated if they are found to pose a health risk.

The epidemiologic evidence for elongate mineral particle (EMP)-related human cancer risk.

Epidemiologic research on the role of fibers and other elongate mineral particles (EMP) and human diseases including cancers has generated a large body of literature over the last decades: nevertheless, there remain some questions for which the scientific community appears unable to reach consensus. Reasons for genuine differences in opinion include (i) ways in which exposures have been classified; (ii) methodological limitations of the available studies, (iii) criteria for the interpretation of study results, including potential underlying biological mechanisms, and (iv) methodology for integrating the evidence. Various approaches have been proposed in recent years to address these issues, which will be illustrated using examples from asbestos, talc, taconite, synthetic mineral fibers and silicon carbide, with emphasis on potential carcinogenic effects. Potential solutions include improved exposure and outcome assessment - including use of biomarkers and other molecular approaches, consideration of potential confounding and other sources of bias, implementation of guidelines for study quality assessment and evidence evaluation and integration.

Mechanistic in vitro studies: What they have told us about carcinogenic properties of elongated mineral particles (EMPs).

In vitro studies using target and effecter cells of mineral-induced cancers have been critical in determining the mechanisms of pathogenesis as well as the properties of elongated mineral particles (EMPs) important in eliciting these responses. Historically, in vitro models of 'mutagenesis' and immortalized cell lines were first used to test the theory that EMPs were mutagenic to cells, and 'genotoxicity', as defined as damage to DNA often culminating in cell death, was observed in a dose-dependent fashion as responses of many cell types to a number of EMPs. As two-stage and multi-step models of cancer development emerged in the 1970s and 1980s, differentiated 3D organ cultures and monolayers of lung epithelial and mesothelial cells were used to probe the mechanisms of cancer development. These studies demonstrated a spectrum of pre-neoplastic changes, including hyperplasia and squamous metaplasia, in response to long (>5 µm in length) needlelike EMPs whereas long, curly chrysotile fibers caused acute cytotoxicity. Shorter fibers of many types were taken up by cells and encompassed in phagolysosomes. Comparative studies using chemical carcinogens showed that chemical agents interacted directly with DNA whereas long EMPs appeared to be promoters of cancers via a number of mechanisms such as inflammation, generation of oxidants, and instigation of cell division. The multitude of these signaling cascades and epigenetic mechanisms of both lung cancers and mesotheliomas have been most recently studied in normal or telomerase immortalized human cells. Importantly, many of these pathways are elicited by long, straight amphibole asbestos fibers or carbon nanotubes in rodents and not by short (<5 µm) EMPs, fragments, or nonfibrous particles. However, the chemistry and surface properties of long fibers are also critical in cell responses to minerals.

A case study of the translocation, bioprocessing and tissue interactions of EMP following inhalation exposure.

Human autopsied lung sections from a resident in the Quebec asbestos region were examined. The study utilized high resolution transmission electron microscopy, scanning transmission electron microscopy (HRTEM/STEM) with the analytical capabilities of electron energy loss spectroscopy (EELS) and energy dispersive spectroscopy (EDS) detectors. We report the first analytical ultrastructural characteristics of EMPs, detailing chemical concentration gradients inside the iron-protein coatings and lateral elemental gradients in the local tissue regions. It is shown that the EMPs are subjected to bioprocessing which involves physicochemical transformations and also an elemental transport mechanism that alters the inhaled EMP as well as the surrounding cellular matrix. At high resolution imaging the iron-rich coating around the EMP was observed to have a distinct channel-like nanostructure with some parallel aligned nanofibrils that are reminiscent of tooth enamel which consists of biomineralized nanocomposites with alternating organic/inorganic matrices.

A comparison of asbestos fiber potency and elongate mineral particle (EMP) potency for mesothelioma in humans.

We analyzed the mesothelioma mortality in cohorts of workers exposed to crocidolite, amosite, and chrysotile to estimate asbestos fiber potency for mesothelioma, using the method of Hodgson and Darnton (2000). We relied on the original 17 cohort studies in their analysis, along with 3 updates of those studies and 3 new asbestos cohort studies published since 2000. We extended the analyses to examine the mesothelioma potency of tremolite in vermiculite from Libby, Montana, and for non-asbestiform elongate mineral particles (EMPs) in taconite iron ore, talc, and South Dakota gold mining. Mesothelioma potency (RMeso) was calculated as the percent of all expected deaths that were due to mesothelioma per fiber/cc-year of exposure.The RMeso was 0.0012 for chrysotile, 0.099 for amosite, and 0.451 for crocidolite: thus, the relative potency of chrysotile:amosite:crocidolite was 1:83:376, which was not appreciably different from the estimates by Hodgson and Darnton in 2000. The RMeso for taconite mining fibers was 0.069 which was slightly smaller than that for amosite. The RMeso for Libby fibers was 0.028 which was greater than that for chrysotile and less than that for amosite. Talc and gold mining EMPs were non-potent for mesothelioma. Although there are a number of methods for estimating fiber potency of asbestos and non-asbestiform EMPs, the method of Hodgson and Darnton provides a uniform method by which fiber potency can be compared across many fiber types. Our estimates of RMeso provide a useful addition to our knowledge of mesothelioma potency for different asbestos and non-asbestiform EMP fibers.

Measurement of elongate mineral particles: What we should measure and how do we do it?

The length distributions of single fibrils of Coalinga, UICC-B and wet dispersed chrysotile were measured by transmission electron microscopy (TEM). It was found that the distributions significantly diverged above approximately 10 µm (µm) in length, corresponding to differences in published results of animal experiments. This result is in contrast to published data in which counting of an insufficient number of fibers resulted in an erroneous conclusion that the length distribution of Coalinga chrysotile fibrils was indistinguishable from those of other sources of chrysotile. The size distributions of the respirable particle size fractions from acknowledged tremolite asbestos samples were found to be dominated by elongate particles longer than 5 µm that are within the dimensional range of non-asbestiform amphiboles. Prior studies have shown that these elongate particles obscure a correlation between a specific size range of particles and results of animal implantation studies that used tremolite of various morphologies. In the prior studies, a reference protocol was developed from four crushed non-asbestiform amphiboles to differentiate the size range of amphibole particles that correlates with the mesothelioma frequencies observed in the animal studies. In the work reported here, this correlation was tested with TEM analyses of amphiboles from Libby, MT, Sparta, NJ and Homestake mine, Lead, SD, which represent known environmental/occupational situations. Further TEM analyses of the tremolite samples used in the original animal implantation studies have also shown that the numbers of elongate tremolite particles with lengths ≤5 µm implanted into the animals are not correlated with the observed mesothelioma frequencies.

Mesothelioma and other lung disease in taconite miners; the uncertain role of non-asbestiform EMP.

The purpose of this paper was to assess the role of non-asbestiform amphibole EMPs in the etiology of mesotheliomas and other lung disease in taconite (iron ore) miners. Increased mesothelioma rates have been described in Minnesota taconite workers since the late 1990s. Currently, over 100 cases have been reported by the Minnesota Department of Health within the complete cohort of miners in Minnesota. Geologic sampling has indicated that only the eastern part of the iron range contains non-asbestiform amphibole elongate mineral particles (EMPs), in close proximity to the ore. This type of EMP has been less studied and also exists in talc and gold mining. A series of investigations into the state's taconite industry have been recently completed. Results from a cohort mortality study indicated an SMR of 2.77 (95% CI = 1.87-3.96) for mesothelioma. In a case-control study, the odds ratio for mesothelioma for high vs. low EMP exposure was 2.25 (5% CI = 1.13-4.5) but EMPs in this study were counted by phase contrast microscopy. Odds ratios were not elevated in mines located in the eastern part of the Mesabi iron range. The overall findings suggest that mesothelioma in taconite miners is related to EMP exposure. Because of the way EMPs were counted, results from these studies cannot allow a firm conclusion about the association between EMP exposure and the reported excess mesothelioma.