The in vitro cytotoxic effects of natural (fibrous epsomite crystals) and synthetic (Epsom salt) magnesium sulfate.

Exposure to mineral fibers represents an occupational and environmental hazard since particulate inhalation leads to several health disorders. However, few data are available on the effect of fibers with high solubility like natural epsomite, a water-soluble fiber with an inhalable size that allows it to penetrate biological systems, with regard to the respiratory tract. This study evaluated the natural (fibrous epsomite) and synthetic (Epsom salt) magnesium sulfate pathogenicity. Investigations have been performed through morpho-functional and biochemical analyses, in an in vitro cell model that usually grows as monocytes, but that under appropriate conditions differentiates into macrophages. These latter, known as alveolar macrophages, if referred to lungs, represent the first line of defense against harmful inhaled stimuli. Morphological observations reveal that, if Epsom salt induces osmotic stress on cell culture, natural epsomite fibers lead to cellular alterations including thickening of the nuclear envelope and degenerated mitochondria. Moreover, the insoluble fraction (impurities) internalized by cells induces diffuse damage characterized at the highest dosage and exposure time by secondary necrosis or necrotic cell death features. Biochemical analyses confirm this mineral behavior that involves MAPK pathway activation, resulting in many different cellular responses ranging from proliferation control to cell death. Epsom salt leads to MAPK/ERK activation, a marker predictive of overall survival. Unlike, natural epsomite induces upregulation of MAPK/p38 protein involved in the phosphorylation of downstream targets driving necrotic cell death. These findings demonstrate natural epsomite toxicity on U937 cell culture, making the inhalation of these fibers potentially hazardous for human health. RESEARCH HIGHLIGHTS: Natural epsomite and synthetic Epsom salt effects have been evaluated in U937 cell model. Epsom salt induces an osmotic cellular stress. Natural epsomite fibers lead to cellular damage and can be considered potentially dangerous for human health.

Could soluble minerals be hazardous to human health? Evidence from fibrous epsomite.

From a toxicological point of view, particulates and fibres with high solubility in water and/or in biological environments have not been considered in detail and the knowledge to date in this area is very scarce. In this study, the water-soluble natural epsomite fibres from Perticara Mine (Italy) were investigated using SEM-EDS, XRPD, ICP-AES and alpha spectrometry measurements which were combined and integrated to characterise the fibres' morphology, crystal chemistry and mineralogy. The morphological and morphometric results showed that most of the fibres are of inhalable size (Dae 5.09 µm) and can be potentially adsorbed from all parts of the respiratory tract. Chemical analysis reveals significant amounts of toxic elements (As, Co, Fe, Mn, Ni, Sr, Ti, Zn) and surprisingly high contents of radioactive isotopes (210Po and 228Th) in epsomite crystals, making the inhalation of these fibres potentially hazardous to human health. Through this study, we want to focus on soluble minerals, such as epsomite, which can be present in both natural and anthropic environments and have never been considered from the point of view of their potential hazard.

Characterisation of potentially toxic natural fibrous zeolites by means of electron paramagnetic resonance spectroscopy and morphological-mineralogical studies.

This study explored the morphological, mineralogical, and physico-chemical features of carcinogenic erionite and other possibly hazardous zeolites, such as mesolite and thomsonite, while also investigating the interacting capability of the mineral surface at the liquid/solid interface. Extremely fibrous erionite is K+ and Ca2+-rich and shows the highest Si/Al ratio (3.38) and specific surface area (8.14 m2/g). Fibrous mesolite is Na+ and Ca2+-rich and displays both a lower Si/Al ratio (1.56) and a smaller specific surface area (1.56 m2/g). The thomsonite composition shows the lowest values of Si/Al ratio (1.23) and specific surface area (0.38 m2/g). Electron paramagnetic resonance data from selected spin probes reveal that erionite has a homogeneous site distribution and interacts well with all spin probes. The surfaces of mesolite and thomsonite are less homogeneous and closer polar sites were found through consequent interaction with the probes. The mesolite surface can also clearly interact but with a lower strength and may represent a potential health hazard for humans, though with a lower degree if compared to erionite. The thomsonite surface is not inert and interacts with the probes with a low-grade capability. We can expect small fragments of thomsonite to interact with the biological environment, though with a low-grade intensity.

Historical and clinical considerations on Ekbom's syndrome.

Ekbom's syndrome represents a relatively uncommon neuropsychiatric condition characterized by the recurrent and bizarre fixed delusional belief to be infested by small organisms or even unanimated materials ('Morgellons disease'), without any objective evidence of infestation/parasitosis. The condition, mainly diagnosed in a nonpsychiatric setting, is supposed to be largely underestimated and, hence, undermanaged. The present comprehensive review aims at investigating Ekbom's syndrome, from a historical, epidemiological, clinical and therapeutic perspective, by providing diagnostic-treatment strategies in managing this condition in routine psychiatric clinical settings. The prototypical patient is a middle-aged woman (or a younger subject in those cases in which substance and/or alcohol abuse is implicated), often single, divorced or widowed (loneliness component and social withdrawal), who has already consulted several specialists due to skin lesions associated with a firm and delusional belief to be infested. The identification and diagnosis are challenging due to poor patient's insight, poor knowledge and collaboration between specialists and differential diagnoses to be considered before asking for a psychiatric referral. Management and treatment strategies mainly derive from isolated case reports or observational studies with a small sample size. Further randomized clinical trials should be performed to evaluate the efficacy of newer antipsychotic drugs, including long-acting injectable formulations.

EPR, TEM and cell viability study of asbestiform zeolite fibers in cell media.

Human monocyte U937 cell line was used as a model to verify the toxicity of erionite and offretite asbestiform zeolite fibers. As a presumed non-toxic reference, a fibrous scolecite zeolite was also used. To analyze the process of fiber ingestion into cells and the cells-fibers interactions, a spin-probe electron paramagnetic resonance (EPR) analysis was performed supported by transmission electron microscopy (TEM) and cell viability measurements as a function of the incubation time. Erionite fibers were fast internalized in the membrane mainly as aggregates with radical-solution drops trapped inside, and were found in the cytosol and at the nucleus. In 24h, first erionite fibers rich in sodium and potassium, and then calcium-rich erionite fibers, induced cell necrosis. The offretite fibers formed rounding electron-dense filaments which transformed in curved filaments, initially perturbing the cell structure and interacting at the external surface more than erionite fibers. Such interactions probably diminished the toxic effect of offretite on cells. Interestingly, the presumed non-toxic scolecite fibers were partially internalized, inducing formation of swollen mitochondria and squared cells. Overall, the toxic effect of the fibrous zeolites was related to fiber morphology, chemical distribution of sites, structural variations and formation of aggregates.

Electron paramagnetic resonance and transmission electron microscopy study of the interactions between asbestiform zeolite fibers and model membranes.

Different asbestiform zeolite fibers of the erionite (termed GF1 and MD8, demonstrated carcinogenic) and offretite (termed BV12, suspected carcinogenic) families were investigated by analyzing the electron paramagnetic resonance (EPR) spectra of selected surfactant spin probes and transmission electron microscopy (TEM) images in the presence of model membranes-cetyltrimethylammonium (CTAB) micelles, egg-lecithin liposomes, and dimyristoylphosphatidylcholine (DMPC) liposomes. This was undertaken to obtain information on interactions occurring at a molecular level between fibers and membranes which correlate with entrance of fibers into the membrane model or location of the fibers at the external or internal membrane interfaces. For CTAB micelles, all fibers were able to enter the micelles, but the hair-like structure and chemical surface characteristics of GF1 modified the micelle structure toward a bilayer-like organization, while MD8 and BV12, being shorter fibers and with a high density of surface interacting groups, partially destroyed the micelles. For liposomes, GF1 fibers partially penetrated the core solution, but DMPC liposomes showed increasing rigidity and organization of the bilayer. Conversely, for MD8 and BV12, the fibers did not cross the membrane demonstrating a smaller membrane structure perturbation. Scolecite fibers (termed SC1), used for comparison, presented poor interactions with the model membranes. The carcinogenicity of the zeolites, as postulated in the series SC1

Geological occurrence, mineralogical characterization, and risk assessment of potentially carcinogenic erionite in Italy.

Erionite is a zeolite representing a well-known health hazard. In fact, exposure of humans to its fibers has been unequivocally associated with occurrence of malignant mesothelioma. For this reason, a multi-methodological approach, based upon field investigation, morphological characterization, scanning electron microscopy (SEM)/energy-dispersive spectroscopy (EDS) chemical analysis, and structure refinement through X-ray powder diffraction (XRPD), was applied to different samples of potentially carcinogenic erionite from Northern Italy. The studied crystals have a chemical composition ranging from erionite-Ca to erionite-Na and display variable morphologies, varying from prismatic, through acicular and fibrous, to extremely fibrous asbestiform habits. The fibrous samples were characterized by an unusual preferred partition of aluminum (Al) at tetrahedral site T1 instead of tetrahedral site T2. Further, a mismatch between the a-parameter of erionite-Ca and levyne-Ca that are intergrown in the asbestiform sample was detected. This misfit was coupled to a relevant micro-strain to maintain structure coherency at the boundary. Erionite occurs in 65% of the investigated sites, with an estimated quantity of 10 to 40 vol% of the associated minerals. The presence of this mineral is of concern for risk to human health, especially if one considers the vast number of quarries and mining-related activities that are operating in the zeolite host rocks. The discovery of fibrous and asbestiform erionite in Northern Italy suggests the need for a detailed risk assessment in all Italian areas showing the same potential hazard, with specific studies such as a quantification of the potentially respirable airborne fibers and targeted epidemiological surveillance.

Potential carcinogenic erionite from Lessini Mounts, NE Italy: Morphological, mineralogical and chemical characterization.

Exposure of humans to erionite fibers of suitable morphology and dimension has been unambiguously linked to the occurrence of malignant mesothelioma. For this reason, a morphological, morphometrical, mineralogical, and chemical investigation was performed on two representative samples of potential carcinogenic, fibrous erionite from Lessini Mounts, northeastern (NE) Italy, which has not apparently been examined previously. The first sample is erionite-Ca with an extremely fibrous, hair-like and flexible appearance, and growth in intimate association with levyne. The second sample is erionite-Ca with prismatic to acicular crystals and rigid behavior, enriched in K(+) and Ca(2+) extra-framework cations. Although erionite is a nominally Fe-free phase, iron (Fe) was detected in low amounts in all the analyzed crystals. In both the investigated samples, erionite is present as individual fibers of respirable size. Considering that the toxicity and carcinogenic potential of erionite is associated with its size parameters, together with its in vivo durability and high surface area, most of the investigated fibers may also be potentially carcinogenic. The presence of erionite in extensively quarried and largely employed volcanic rocks, suggesting the need for detailed health-based studies in the region.

Morpho-chemical characterization and surface properties of carcinogenic zeolite fibers.

Erionite belonging to the zeolite family is a human health-hazard, since it was demonstrated to be carcinogenic. Conversely, offretite family zeolites were suspected carcinogenic. Mineralogical, morphological, chemical, and surface characterizations were performed on two erionites (GF1, MD8) and one offretite (BV12) fibrous samples and, for comparison, one scolecite (SC1) sample. The specific surface area analysis indicated a larger availability of surface sites for the adsorption onto GF1, while SC1 shows the lowest one and the presence of large pores in the poorly fibrous zeolite aggregates. Selected spin probes revealed a high adsorption capacity of GF1 compared to the other zeolites, but the polar/charged interacting sites were well distributed, intercalated by less polar sites (Si-O-Si). MD8 surface is less homogeneous and the polar/charged sites are more interacting and closer to each other compared to GF1. The interacting ability of BV12 surface is much lower than that found for GF1 and MD8 and the probes are trapped in small pores into the fibrous aggregates. In comparison with the other zeolites, the non-carcinogenic SC1 shows a poor interacting ability and a lower surface polarity. These results helped to clarify the chemical properties and the surface interacting ability of these zeolite fibers which may be related to their carcinogenicity.