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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 m

Re: Ilgren EB, Pooley FD, Kumiya YM, Hoskins JA Critical reappraisal of Balangero chrysotile and mesothelioma risk. Epidemiology Biostatistics and Public Health. 2015; 12:e10125-1

Background: Silica continues to represent an intriguing topic of fundamental and applied research across various scientific fields, from geology to physics, chemistry, cell biology, and particle toxicology. The pathogenic activity of silica is variable, depending on the physico-chemical features of the particles. In the last 50 years, crystallinity and capacity to generate free radicals have been recognized as relevant features for silica toxicity. The ‘surface’ also plays an important role in silica toxicity, but this term has often been used in a very general way, without defining which properties of the surface are actually driving toxicity. How the chemical features (e.g., silanols and siloxanes) and configuration of the silica surface can trigger toxic responses remains incompletely understood. Main body: Recent developments in surface chemistry, cell biology and toxicology provide new avenues to improve our understanding of the molecular mechanisms of the adverse responses to silica particles. New physicochemical methods can finely characterize and quantify silanols at the surface of silica particles. Advanced computational modelling and atomic force microscopy offer unique opportunities to explore the intimate interactions between silica surface and membrane models or cells. In recent years, interdisciplinary research, using these tools, has built increasing evidence that surface silanols are critical determinants of the interaction between silica particles and biomolecules, membranes, cell systems, or animal models. It also has become clear that silanol configuration, and eventually biological responses, can be affected by impurities within the crystal structure, or coatings covering the particle surface. The discovery of new molecular targets of crystalline as well as amorphous silica particles in the immune system and in epithelial lung cells represents new possible toxicity pathways. Cellular recognition systems that detect specific features of the surface of silica particles have been identified. Conclusions: Interdisciplinary research bridging surface chemistry to toxicology is progressively solving the puzzling issue of the variable toxicity of silica. Further interdisciplinary research is ongoing to elucidate the intimate mechanisms of silica pathogenicity, to possibly mitigate or reduce surface reactivity. Keywords: Silica, Silicosis, Lung cancer, Auto-immune diseases, Surface reactivity, Silanol, Coating, Modelling, Spectroscopy, Atomic force microscopy

Exposure to natural occurrences of asbestos (NOA) and other potentially hazardous elongated mineral particles (EMPs) may pose a risk to human health and the environment. Weathering forces and anthropic activities may alter the cohesion of NOA-bearing outcrops and disperse EMPs in air, water, and soil. The current paradigm for fibre toxicity indicates that morphology and crystal chemistry are key parameters in determining the toxicological properties of a mineral. This work aims to assess and discuss the impact of sub-tropical supergene alteration and weathering on the morphology and the chemical composition of antigorite, a non-regulated serpentine that shares chemical composition with asbestos chrysotile. Antigorite naturally occurring in lateritic Ni ores of New Caledonia exhibits a unique asbestos-like habit at the microscopic scale. Standardized mechanical stress was performed on antigorites, selected to represent different cohesion states. The specimens produced a relevant amount of respirable fibres, between 32 and 42% (WHO counting criteria). PCA on chemical data and ternary diagrams show that all antigorites exhibit a similar Si content (from 2.05 to 2.09 a.f.u.) but were mainly differentiated by Mg and Ni content, ranging from 2.66 to 2.80 and 0.00 to 0.09 a.f.u., respectively. Si content in Caledonian antigorite is higher than Si in non-lateritic samples. This suggests that a main alteration process occurred after the obduction of the ultramafic protolith. The supergene alteration determined the Ni enrichment of lateritic deposits and is likely the main cause of the mineral alteration of antigorite under sub-tropical environments. Further, weathering processes prompt the disaggregation of altered antigorite causing the generation and dispersion of respirable, potentially hazardous, antigorite fibres in the environment.

The rising awareness about the risk due to asbestos environmental exposure has led to a new interest in the investigation of non-regulated mineral fibers. Evidence of chronic diseases has been described in individuals exposed to naturally occurring asbestiform (NOA) minerals in Turkey (erionite), Italy (fluoro-edenite), and the United States (winchite/richterite). In New Caledonia, an increased incidence of asbestos-related diseases was correlated with the natural occurrence of fibrous serpentines chrysotile and fibro-lamellar antigorite in outcrops, roadways, and soils. A minor amount of tremolite asbestos was also observed, increasing the health hazard. By adopting a precautionary principle, New Caledonia legislation classified antigorite as regulated asbestos, even if limited toxicity assessment is available. Caledonian antigorite exhibits a wide range of natural shapes, morphologies, and degrees of alteration as a result of pedogenic alteration induced by subtropical conditions. As the alteration increases, lamellar antigorite gradually cleaves into fibrous-like particles, assuming a fibro-lamellar habit. An increase in the emission of inhalable (potentially asbestiform) fibers in air was observed. To understand this mechanism, a multidisciplinary mineralogical and geochemical investigation was carried out. Additionally, several in vitro tests have been performed on three antigorite samples, subjected to different levels of alteration, to collect preliminary information on antigorite toxicity. Alteration modifies the surface reactivity of antigorite. The circulation of fluids induces a mechanical stress and an elemental exchange at mineral/water interface, promoting the loss of cohesion of the mineral structure and affecting the surface chemistry and toxicity of fibrous (asbestiform) antigorite.

Significance Silica particles with a population of nearly free silanols damage cellular membranes and initiate inflammatory reactions. Nearly free silanols are found on the surface of both fractured quartz and amorphous silica particles, and their occurrence initiates the toxicity of silica, thus revisiting the ancient paradigm whereby crystallinity is critical for silica toxicity. This finding resolves the lingering questions about the origin and the variability of the toxicity of silica particles. The discovery of the biological activity of nearly free silanols opens perspectives for the prevention of silicosis through a safer-by-design approach, and will have an impact on other fields that involve interfacial phenomena, including biomaterial design, nanofabrication, and catalysis., Inhalation of silica particles can induce inflammatory lung reactions that lead to silicosis and/or lung cancer when the particles are biopersistent. This toxic activity of silica dusts is extremely variable depending on their source and preparation methods. The exact molecular moiety that explains and predicts this variable toxicity of silica remains elusive. Here, we have identified a unique subfamily of silanols as the major determinant of silica particle toxicity. This population of “nearly free silanols” (NFS) appears on the surface of quartz particles upon fracture and can be modulated by thermal treatments. Density functional theory calculations indicates that NFS locate at an intersilanol distance of 4.00 to 6.00 Å and form weak mutual interactions. Thus, NFS could act as an energetically favorable moiety at the surface of silica for establishing interactions with cell membrane components to initiate toxicity. With ad hoc prepared model quartz particles enriched or depleted in NFS, we demonstrate that NFS drive toxicity, including membranolysis, in vitro proinflammatory activity, and lung inflammation. The toxic activity of NFS is confirmed with pyrogenic and vitreous amorphous silica particles, and industrial quartz samples with noncontrolled surfaces. Our results identify the missing key molecular moieties of the silica surface that initiate interactions with cell membranes, leading to pathological outcomes. NFS may explain other important interfacial processes involving silica particles.

Conventional nanotoxicological assays are subjected to various interferences with nanoparticles and especially carbon nanotubes. A multiparametric flow cytometry (FCM) methodology was developed here as an alternative to quantify oxidative stress, mitochondrial impairment, and later cytotoxic and genotoxic events. The experiments were conducted on RAW264.7 macrophages, exposed for 90 min or 24 h-exposure with three types of multiwalled carbon nanotubes (MWCNTs): pristine (Nanocyl&trade, CNT), acid functionalized (CNTf), or annealed treatment (CNTa). An original combination of reactive oxygen species (ROS) probes allowed the simultaneous quantifications of broad-spectrum ROS, superoxide anion (O2&bull, &minus, ), and hydroxyl radical (&bull, OH). All MWCNTs types induced a slight increase of broad ROS levels regardless of earlier antioxidant catalase activity. CNTf strongly stimulated the O2&bull, production. The &bull, OH production was downregulated for all MWCNTs due to their scavenging capacity. The latter was quantified in a cell-free system by electron paramagnetic resonance spectroscopy (EPR). Further FCM-based assessment revealed early biological damages with a mitochondrial membrane potential collapse, followed by late cytotoxicity with chromatin decondensation. The combined evaluation by FCM analysis and cell-free techniques led to a better understanding of the impacts of MWCNTs surface treatments on the oxidative stress and related biological response.

Among the physico-chemical features responsible for the so-called “variability of quartz hazard”, a key role has been assigned to the silica surface charge, evaluated by means of ζ potential measurement. The ζ potential of silica describes the protonation state of silanols which, in turn, determine interactions with cell membranes. To gain a molecular understanding of the role of silanols in silica pathogenicity, we conducted a systematic investigation of the variation of the ζ potential as a function of pH (ζ plot titration curve) on a large set of respirable quartz particles with different levels of metal contaminants. The membranolytic activity of the particles on red blood cells, used as a readout of pathogenic activity, was assessed in parallel. Pure quartz surfaces showed sigmoid-shaped ζ plots suggesting the presence of silanol families with similar acidity, whereas contaminated dusts exhibited convex-shaped ζ plots, indicating a higher silanol heterogeneity on contaminated surfaces with respect to the pure ones. The quartz particles with a higher surface heterogeneity related to metal contamination showed a higher membranolytic activity. By removing structural defects and chemical heterogeneity, the ζ plot shifted towards the typical shape of pure quartz and the membranolytic activity was reduced. We conclude that the ζ plot is a useful readout to measure the acid-base behavior of quartz surfaces and to describe the chemical heterogeneity of quartz silanols. Surface heterogeneity, here induced by metal contamination, is proposed as the main cause of quartz membranolytic activity, further supporting the hypothesis that surface silanol disorganization determines silica pathogenicity.

Suite notamment au signalement par plusieurs agences nationales et internationales de cas de silicose aigue survenant apres l’usinage de pierres reconstituees contenant des teneurs elevees en quartz (> 85 %), l’Anses s’est auto-saisie et a mis en place un groupe de travail afin de mettre a jour l’ensemble des connaissances concernant les risques pour la sante des professionnels exposes a la silice cristalline. Cette demarche, outre une etude de filieres et la caracterisation de l’exposition des travailleurs, visait plus particulierement a faire le point sur les effets sanitaires, en particulier cancerigenes de la silice cristalline et sur les pistes de prevention. Concernant plus specifiquement la question des effets sanitaires associes a la silice cristalline, une synthese de rapports institutionnels a ete realisee, puis completee par une analyse critique, selon une methode standardisee de lecture et d’evaluation (R-AMSTAR), des revues publiees dans la litterature scientifique depuis la parution de ces rapports. Certaines questions, nouvelles ou peu documentees, ont fait l’objet d’une revue narrative sur la base des articles originaux collectes jusqu’a la fin de l’expertise. Par ailleurs, l’expertise de l’Anses a beneficie d’un regard socio-historique replacant la demarche d’expertise menee par le groupe dans la longue histoire de l’etude et de la reconnaissance des pathologies professionnelles associees a la silice cristalline. L’Anses a ainsi evalue les effets sanitaires de la silice cristalline et plus particulierement les differentes formes de silicose, la relation silice–cancer bronchique, y compris en l’absence de silicose, les cancers extra-pulmonaires, l’ensemble des pathologies respiratoires non malignes, les pathologies auto-immunes, et les atteintes renales. L’Anses a egalement analyse les principaux mecanismes de toxicite associes aux poussieres en general, et a la silice cristalline en particulier. Des developpements specifiques ont notamment ete consacres a la silice fraichement fracturee, et aux particules ultra fines (PUF). L’Anses a propose plusieurs recommandations, en particulier sur la prevention medicale, la valeur limite d’exposition professionnelle (VLEP) et les tableaux de maladies professionnelles. Une synthese des donnees relatives aux effets sanitaires associes a des expositions a la silice cristalline et des principales recommandations en matiere de prevention sera presentee lors du Congres. Deux autres presentations sont consacrees a la caracterisation des expositions a la silice cristalline en France et a l’adaptation de la methode R-Amstar aux etudes epidemiologiques et toxicologiques realisees dans le cadre de cette expertise.

New outbursts of silicosis were recently reported among workers manufacturing an engineered material known as "artificial stone," composed by high percentages of quartz (up to 98%) agglomerated with pigments and polymeric resins. Dusts released by abrasion during artificial stone polishing were characterized for particle size, morphology, and elemental composition and studied for (1) ability to catalyze free radical generation in acellular tests, (2) membranolytic potential on human erythrocytes, (3) cytotoxic activity (lactate dehydrogenase release) on murine alveolar macrophages (MH-S) and human bronchial epithelial (BEAS-2B) cell lines, (4) induction of epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Min-U-Sil 5 was used as reference quartz. Artificial stone dusts exhibited morphological features close to quartz, but contained larger amount of metal transition ions (mainly, Fe, Cu, and Ti), potentially responsible for the high reactivity in free radical generation observed. Opposite to Min-U-Sil 5, they were neither hemolytic nor cytotoxic on MH-S cells, a low cytotoxicity only being observed with BEAS-2B cells. The presence on the particle surface of residues of the resin accounts for this attenuated behavior, as hemolysis appeared and cytotoxicity increased after thermal degradation of the resin, when the free quartz surface was exposed. All dusts induced EMT with loss of E-cadherin expression and increased the expression of mesenchymal proteins (α-smooth muscle actin and vimentin). This may contribute to explain the development of fibrosis on workers exposed to artificial stone dusts.

Resume Dans le cadre de son expertise collective visant evaluer les risques pour la sante des travailleurs exposes a la silice cristalline en France, l’Anses a mis a jour de l’ensemble des connaissances concernant les risques pour la sante des professionnels exposes a la silice cristalline. Cette demarche, outre une etude de filieres et la caracterisation de l’exposition des travailleurs, visait plus particulierement a faire le point sur les effets sanitaires, en particulier cancerigenes de la silice cristalline et sur les pistes de prevention. Concernant plus specifiquement la question des effets sanitaires associes a la silice cristalline, le groupe de travail (GT) mis en place par l’Anses a tout d’abord procede a une synthese de rapports institutionnels. Concernant la silicose et le cancer bronchopulmonaire, cette synthese a ete completee par une analyse critique des revues de synthese publiees dans la litterature scientifique depuis la parution de ces rapports. Les autres types d’effets et notamment certaines questions, nouvelles ou peu documentees, ont fait l’objet d’une revue narrative sur la base des articles originaux collectes jusqu’a la fin de l’expertise. Pour realiser l’analyse critique des revues de synthese portant sur la silicose et le cancer bronchopulmonaire en lien avec une exposition a la silice cristalline, le GT s’est appuye sur une methode standardisee de lecture et d’evaluation (R-AMSTAR) qu’il a adaptee. Cette methode, initialement developpee par des chercheurs universitaires pour analyser la qualite methodologique des revues systematiques d’essais cliniques, repose sur un principe de cotation de 11 items au travers de differents criteres definis. Ces items portent notamment sur les modalites de recherche documentaire, de selection des etudes et d’extraction des donnees, sur les conditions d’inclusion des etudes dans la synthese, etc. Le score final permet de classer differentes revues systematiques portant sur un meme sujet selon leur qualite methodologique. Le GT a modifie certains criteres d’evaluation et elabore des regles de decisions afin d’analyser la qualite methodologique des revues de synthese epidemiologiques et toxicologiques relatives aux effets de la silice cristalline dans le domaine de la sante au travail.

Dans le cadre de son expertise collective visant evaluer les risques pour la sante des travailleurs exposes a la silice cristalline en France, l’Anses a realise une caracterisation des expositions a la silice cristalline par secteur d’activite en s’appuyant sur les donnees de mesures d’exposition disponibles dans les bases de donnees Colchic® et Scola® et sur les donnees de prevalence d’exposition issues des enquetes SUMER 2010 et 2017. Ce travail a permis d’identifier les secteurs d’activite, les tâches et les metiers pour lesquels les niveaux d’exposition excedent certains seuils. Les seuils pris en compte correspondent a la valeur limite d’exposition professionnelle (VLEP-8 h) reglementaire en France pour le quartz (0,1 mg.m−3), a la VLEP-8 h recommandee pour la silice cristalline par differents organismes dont le SCOEL et l’OSHA (0,05 mg.m−3), et a la VLEP-8 h la plus basse actuellement definie par l’ACGIH et retenue comme seuil d’action par l’OSHA (0,025 mg.m−3). D’autres sources de donnees ont egalement ete investiguees en vue d’evaluer les expositions professionnelles a la silice cristalline notamment les matrices emplois expositions disponibles et une revue de la litterature scientifique. Par ailleurs, une synthese des donnees disponibles relatives aux expositions a des particules ultrafines de silice cristalline a ete realisee. Ainsi, en France pres de 365 000 travailleurs seraient exposes par inhalation a la silice cristalline, en particulier au quartz. Selon la methode suivie, entre 23 000 et 30 000 salaries seraient exposes au-dela de 0,1 mg.m−3. L’ensemble des donnees d’exposition convergent pour indiquer que quatre secteurs d’activite sont plus particulierement concernes, avec des niveaux d’exposition a la silice cristalline plus eleves et des depassements frequents des valeurs limites actuelles : La construction, La fabrication de produits mineraux non metalliques, la metallurgie et les industries extractives. Une presentation de ces resultats, sera realisee apres un rappel sur les enjeux lies aux methodes de mesures d’exposition a la silice cristalline. Enfin, les principales recommandations emises par l’Anses en matiere de prevention et portant sur les expositions a la silice cristalline seront exposees. Deux autres presentations sont consacrees a l’analyse des donnees relatives aux effets sanitaires associes a des expositions a la silice cristalline et a l’adaptation de la methode standardisee de lecture et d’evaluation des revues de syntheses scientifiques (R-Amstar) aux etudes epidemiologiques et toxicologiques realisees dans le cadre de cette expertise.

Le programme « ABP, Amiante et bonnes pratiques », a proposé une étude intégrée et pluridisciplinaire depuis l’identification jusqu’au caractère pathogène des fibres issues des minéraux amiantifères présents en secteur minier néo-calédonien.- Au travers d’un échantillonnage d’un panel représentatif des asbestes présents (famille des serpentinites et des amphiboles), les minéralogies, les propriétés physico-chimiques et toxicologiques de ces minéraux amiantifères ont été caractérisées.- À noter que le programme ABP a apporté les premières données toxicologiques sur les fibres d’amiante néo-calédoniennes. Un intérêt particulier est porté sur l’antigorite, minéral fibreux très présent sur le territoire calédonien, notamment en secteur minier, mais non répertorié comme amiante dans la législation hors territoire.

Titanium dioxide (TiO 2 ) is widely used as ingredient in several products in the nanoform. TiO 2 -nanoparticles (NPs) are also currently studied for different medical applications. A large debate exists on possible adverse health effects related to their exposure. While there is some evidence of TiO 2 -NP central nervous system toxicity, their effects on peripheral neurons have been poorly explored. In this study we investigated the effects of TiO 2 -NPs on dorsal root ganglion (DRG) sensory neurons and satellite glial cells that may be reached by nanoparticles from the bloodstream. We found that TiO 2 -NPs are internalized in DRG cells and induce apoptosis in a dose dependent manner in both types of cells, ROS production and changes in expression of proinflammatory cytokine IL-1β. Furthermore, we found that the axonal retrograde transport is altered in neurons upon exposure to TiO 2 -NPs. Overall, the results indicate a potential neurotoxic effect of TiO 2 -NPs on DRG cells. From the Clinical Editor Exposure to titanium dioxide nanoparticles is increasing in medical practice. Little is known about their potential toxic effects on the peripheral nervous system. The authors studied this aspect and showed that titanium nanoparticles might potentially cause toxicity over long term.

Background The eruptions of Eyjafjallajökull (2010) and Grímsvötn (2011), Iceland, triggered immediate, international consideration of the respiratory health hazard of inhaling volcanic ash, and prompted the need to estimate the potential hazard posed by future eruptions of Iceland’s volcanoes to Icelandic and Northern European populations. Methods A physicochemical characterization and toxicological assessment was conducted on a suite of archived ash samples spanning the spectrum of past eruptions (basaltic to rhyolitic magmatic composition) of Icelandic volcanoes following a protocol specifically designed by the International Volcanic Health Hazard Network. Results Icelandic ash can be of a respirable size (up to 11.3 vol.% < 4 μm), but the samples did not display physicochemical characteristics of pathogenic particulate in terms of composition or morphology. Ash particles were generally angular, being composed of fragmented glass and crystals. Few fiber-like particles were observed, but those present comprised glass or sodium oxides, and are not related to pathogenic natural fibers, like asbestos or fibrous zeolites, thereby limiting concern of associated respiratory diseases. None of the samples contained cristobalite or tridymite, and only one sample contained quartz, minerals of interest due to the potential to cause silicosis. Sample surface areas are low, ranging from 0.4 to 1.6 m2 g−1, which aligns with analyses on ash from other eruptions worldwide. All samples generated a low level of hydroxyl radicals (HO•), a measure of surface reactivity, through the iron-catalyzed Fenton reaction compared to concurrently analyzed comparative samples. However, radical generation increased after ‘refreshing’ sample surfaces, indicating that newly erupted samples may display higher reactivity. A composition-dependent range of available surface iron was measured after a 7-day incubation, from 22.5 to 315.7 μmol m−2, with mafic samples releasing more iron than silicic samples. All samples were non-reactive in a test of red blood cell-membrane damage. Conclusions The primary particle-specific concern is the potential for future eruptions of Iceland’s volcanoes to generate fine, respirable material and, thus, to increase ambient PM concentrations. This particularly applies to highly explosive silicic eruptions, but can also hold true for explosive basaltic eruptions or discrete events associated with basaltic fissure eruptions., This work was funded under the UK Natural Environment Research Council (NERC) Knowledge Exchange (KE) Fellowship NE/J500525/1 granted to R.E. Holdsworth at Durham University. DED was additionally supported by the ERC Advanced Grant no. 247076 awarded to D.B. Dingwell at LMU Munich.

The variability of quartz hazard stands as one of the most puzzling issues in particle toxicology, notwithstanding the fact that silicosis, the most ancient occupational disease, was the very topic from which the study of the toxicity of particulates developed. Over the years, other adverse effects of silica particles (i.e., lung cancer and autoimmune diseases) were detected and described. However, a few gaps are still present in the physicochemical determinants and cellular pathways involved in the mechanisms of silica pathogenicity. In this perspective, we illustrate how pooling together studies in occupational health and nanotoxicology might fill such gaps, yielding a consistent picture of what imparts toxicity to a given silica source. Recent investigations have shown that crystallinity is not implied in the pathogenic process of silica per se, while patches of disorganized silanols at the surface of both crystalline and amorphous particles can promote membrane damage and inflammation, a process at the origin of silica-related diseases. Introducing these new findings into the accepted multistep model of silica pathogenicity, we obtain a picture of the chemical features of silica governing each cellular step in agreement with the outcomes of major previous studies. We ascribe the origin of the variability of silica hazard mainly to the distribution of various moieties at the particle surface, with silanols playing the major role. Toxicity turns out to be likely predictable by an ad hoc surface characterization. Tailored modifications of the surface can be envisaged to prepare safe materials or blunt toxicity in existing ones.

Ce rapport présente la synthèse, issue du rapport scientifique final, des résultats du programme « ABP, Amiante et bonnes pratiques ».- Le programme ABP a proposé une étude intégrée et pluridisciplinaire depuis l’identification jusqu’au caractère pathogène des fibres issues des minéraux amiantifères présents en secteur minier néo-calédonien.- Au travers d’un échantillonnage d’un panel représentatif des asbestes présents (famille des serpentinites et des amphiboles), les minéralogies, les propriétés physico-chimiques et toxicologiques de ces minéraux amiantifères ont été caractérisées.- À noter que le programme ABP a apporté les premières données toxicologiques sur les fibres d’amiante néo-calédoniennes. Un intérêt particulier est porté sur l’antigorite, minéral fibreux très présent sur le territoire calédonien, notamment en secteur minier, mais non répertorié comme amiante dans la législation hors territoire.

International audience; Silicon carbide (SiC) an industrial-scale product manufactured through the Acheson process, is largely employed in various applications. Its toxicity has been poorly investigated. Our study aims at characterizing the physico-chemical features and the in vitro impact on biological activity of five manufactured SiC powders: two coarse powders (SiC C1/C2), two fine powders (SiC F1/F2) and a powder rich in iron impurities (SiC I). RAW 264.7 macrophages were exposed to the different SiC particles and the cellular responses were evaluated. Contrary to what happens with silica, no SiC cytotoxicity was observed but pro-oxidative and pro-inflammatory responses of variable intensity were evidenced. Oxidative stress (H2O2 production) appeared related to SiC particle size, while iron level regulated pro-inflammatory response (TNFα production). To investigate the impact of surface reactivity on the biological responses, coarse SiC C1 and fine SiC F1 powders were submitted to different thermal treatments (650 to 1400°C) in order to alter the oxidation state of the particle surface. At 1400°C a decrease in TNFα production and an increase in HO., COO.- radicals production were observed in correlation with the formation of a surface layer of crystalline silica. Finally, a strong correlation was observed between surface oxidation state and in vitro toxicity.

The assay of the toxic effects of carbon nanotubes (CNTs) on human health is a stringent need in view of their expected increasing exploitation in industrial and biomedical applications. Most studies so far have been focused on lung toxicity, as the respiratory tract is the main entry of airborne particulate, but there is also recent evidence on the existence of toxic effects of multiwalled carbon nanotubes (MWCNTs) on neuronal and neuroendocrine cells (Belyanskaya et al., 2009; Xu et al., 2009; Gavello et al., 2012). Commercial MWCNTs often contain large amounts of metals deriving from the catalyst used during their synthesis. Since metals, particularly iron, may contribute to the toxicity of MWCNTs, we compared here the effects of two short MWCNTs samples (

Ashfall into heavily populated areas during the October–November 2010 eruption of Merapi volcano, Indonesia created anxiety regarding the growing impacts to health as the eruption escalated and the hazard zone widened. We made a preliminary assessment of the respiratory hazards to human health of the tephra deposits (ashfall, lahar, and PDC surge) from the eruption using a laboratory protocol specifically developed to study the toxic potential of volcanic ash particles. Twenty samples collected from a range of locations were analysed for health-pertinent mineralogical parameters (grain size, crystalline silica content, morphology, surface area, bulk chemistry, and leachable elements) and bio-reactivity (hydroxyl radical generation, haemolytic potential, oxidative capacity, pro-inflammatory response). The grain size pertinent to respiratory health was variable, ranging from 1.4–15.6 vol.% sub-4 μm and 3.0–28.9 vol.% sub-10 μm diameter material. No fibre-like particles were observed. Cristobalite was present in all samples, ranging from 1.9–9.5 wt.%, but surface reactivity and in vitro toxicity assays showed low reactivity for all samples tested. The risk of direct exposure to ash from fallout was in any case low due to seasonal rains limiting its re-suspension and the immediate and effective clean-up of communities by local people who supplied the ash to the Indonesian construction industry for use as aggregate. However, mining of the lahar and thick PDC deposits in the valleys draining the volcano is performed on a vast, industrial scale, which could result in high occupational exposure to thousands of sand miners at Merapi during the dry seasons. Further study of the health hazard of the mined Merapi deposits is warranted

Industrial processing of materials containing quartz induces physico-chemical modifications that contribute to the variability of quartz hazard in different plants. Here, modifications affecting a quartz-rich sand during cast iron production, have been investigated. Composition, morphology, presence of radicals associated to quartz and reactivity in free radical generation were studied on a raw sand and on a dust recovered after mould dismantling. Additionally, cytotoxicity of the processed dust and ROS and NO generation were evaluated on MH-S macrophages. Particle morphology and size were marginally affected by casting processing, which caused only a slight increase of the amount of respirable fraction. The raw sand was able to catalyze OH and CO2(-) generation in cell-free test, even if in a lesser extent than the reference quartz (Min-U-Sil), and shows hAl radicals, conventionally found in any quartz-bearing raw materials. Enrichment in iron and extensive coverage with amorphous carbon were observed during processing. They likely contributed, respectively, to increasing the ability of processed dust to release CO2- and to suppressing OH generation respect to the raw sand. Carbon coverage and repeated thermal treatments during industrial processing also caused annealing of radiogenic hAl defects. Finally, no cellular responses were observed with the respirable fraction of the processed powder.

Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.

Background Exposure to some - but not all - quartz particles is associated to silicosis, lung cancer and autoimmune diseases. What imparts pathogenicity to any single quartz source is however still unclear. Crystallinity and various surface features are implied in toxicity. Quartz dusts used so far in particle toxicology have been obtained by grinding rocks containing natural quartz, a process which affects crystallinity and yields dusts with variable surface states. To clarify the role of crystallinity in quartz pathogenicity we have grown intact quartz crystals in respirable size. Methods Quartz crystals were grown and compared with a fractured specimen obtained by grinding the largest synthetic crystals and a mineral quartz (positive control). The key physico-chemical features relevant to particle toxicity - particle size distribution, micromorphology, crystallinity, surface charge, cell-free oxidative potential - were evaluated. Membranolysis was assessed on biological and artificial membranes. Endpoints of cellular stress were evaluated on RAW 264.7 murine macrophages by High Content Analysis after ascertaining cellular uptake by bio-TEM imaging of quartz-exposed cells. Results Quartz crystals were grown in the submicron (n-Qz-syn) or micron (μ-Qz-syn) range by modulating the synthetic procedure. Independently from size as-grown quartz crystals with regular intact faces did not elicit cellular toxicity and lysosomal stress on RAW 264.7 macrophages, and were non-membranolytic on liposome and red blood cells. When fractured, synthetic quartz (μ-Qz-syn-f) attained particle morphology and size close to the mineral quartz dust (Qz-f, positive control) and similarly induced cellular toxicity and membranolysis. Fracturing imparted a higher heterogeneity of silanol acidic sites and radical species at the quartz surface. Conclusions Our data support the hypothesis that the biological activity of quartz dust is not due to crystallinity but to crystal fragmentation, when conchoidal fractures are formed. Besides radical generation, fracturing upsets the expected long-range order of non-radical surface moieties - silanols, silanolates, siloxanes - which disrupt membranes and induce cellular toxicity, both outcomes associated to the inflammatory response to quartz. Electronic supplementary material The online version of this article (doi:10.1186/s12989-016-0136-6) contains supplementary material, which is available to authorized users.

Amorphous silicas, opposite to crystalline polymorphs, have been regarded so far as nonpathogenic, but few studies have addressed the toxicity of the wide array of amorphous silica forms. With the advent of nanotoxicology, there has been a rising concern about the safety of silica nanoparticles to be used in nanomedicine. Here, we report a study on the toxicity of amorphous nanostructured silicas obtained with two different preparation procedures (pyrolysis vs. precipitation), the pyrogenic in two very different particle sizes, in order to assess the role of size and origin on surface properties and on the cell damage, oxidative stress, and inflammatory response elicited in murine alveolar macrophages. A quartz dust was employed as positive control and monodispersed silica spheres as negative control. Pyrogenic silicas were remarkably more active than the precipitated one as to cytotoxicity, reactive oxygen species production, lipid peroxidation, nitric oxide synthesis, and production of tumor necrosis factor-α, when compared both per mass and per unit surface. Between the two pyrogenic silicas, the larger one was the more active. Silanols density is the major difference in surface composition among the three silicas, being much larger than the precipitated one as indicated by joint calorimetric and infrared spectroscopy analysis. We assume here that full hydroxylation of a silica surface, with consequent stable coverage by water molecules, reduces/inhibits toxic behavior. The preparation route appears thus determinant in yielding potentially toxic materials, although the smallest size does not always correspond to an increased toxicity.

Sugarcane combustion generates fine-grained particulate that has the potential to be a respiratory health hazard because of its grain size and composition. In particular, conversion of amorphous silica to crystalline forms during burning may provide a source of toxic particles. In this study, we investigate and evaluate the toxicity of sugarcane ash and bagasse ash formed from commercial sugarcane burning. Experiments to determine the main physicochemical properties of the particles, known to modulate biological responses, were combined with cellular toxicity assays to gain insight into the potential reactions that could occur at the particle-lung interface following inhalation. The specific surface area of the particles ranged from ∼16 to 90 m(2) g(-1) . The samples did not generate hydroxyl- or carbon-centered radicals in cell-free tests. However, all samples were able to 'scavenge' an external source of hydroxyl radicals, which may be indicative of defects on the particle surfaces that may interfere with cellular processes. The bioavailable iron on the particle surfaces was low (2-3 μmol m(-2) ), indicating a low propensity for iron-catalyzed radical generation. The sample surfaces were all hydrophilic and slightly acidic, which may be due to the presence of oxygenated (functional) groups. The ability to cause oxidative stress and membrane rupture in red blood cells (hemolysis) was found to be low, indicating that the samples are not toxic by the mechanisms tested. Cytotoxicity of sugarcane ash was observed, by measuring lactate dehydrogenase release, after incubation of relatively high concentrations of ash with murine alveolar macrophage cells. All samples induced nitrogen oxide release (although only at very high concentrations) and reactive oxygen species generation (although the bagasse samples were less potent than the sugarcane ash). However, the samples induced significantly lower cytotoxic effects and nitrogen oxide generation when compared with the positive control.

Regular eruptions from Sakurajima volcano, Japan, repeatedly cover local urban areas with volcanic ash. The frequency of exposure of local populations to the ash led to substantial concerns about possible respiratory health hazards, resulting in many epidemiological and toxicological studies being carried out in the 1980s. However, very few mineralogical data were available for determination of whether the ash was sufficiently fine to present a respiratory hazard. In this study, we review the existing studies and carry out mineralogical, geochemical and toxicological analyses to address whether the ash from Sakurajima has the potential to cause respiratory health problems. The results show that the amount of respirable (

Nanomaterials often act as a double sword. On the one hand they offer exceptional new properties, but on the other hand show signs of toxicity. High aspect ratio nanomaterials (HARNs) cause more concern than isometric nanoparticles owing to their physical similarity with asbestos. Many compounds may be prepared in fibrous shape with nano-sized diameter differing one from the other in various ways. This article reports a comparative picture of the chemical features and related toxic responses to a variety of HARNs, namely carbon nanotubes, asbestos, carbon nanofibers, oxide and metal wires and rods. In spite of similarities in form, durability and several biological responses elicited in vitro and in vivo, carbon nanotubes – opposite to asbestos – quench radicals, are hydrophobic and may be fully purified from metal impurities. Most of the other HARNs produced so far are metal or metal oxide compounds, less biopersistent than carbon nanotubes.

Nanotoxicology studies require investigations of several physico-chemical aspects of the particle/body fluid interaction, here described by reviewing recent literature in the light of new experimental data. Current characterization mostly covers morphology and metric-related characteristics (form, chemical composition, specific surface area, primary particle size and size distribution), and is mandatory in any experimental study. To unveil toxicity mechanisms, several other physico-chemical properties relevant to (geno) toxicity need to be assessed, typically the release or quenching of radical/ROS (Reactive Oxygen Species), the presence of active metal ions, evidence of structural defects. Major tasks for physical chemists working on nanoparticles-induced genotoxicity are described with some examples: (i), Tailored preparation of the same material in different sizes; (ii) particle modification changing a single property at a time; and (iii) identification of appropriate reference materials. Phenomena occurring during the contact between nanoparticles and cellular media or biological fluids (dispersion, agglomeration/aggregation, protein adsorption) are discussed in relation to the surface properties of the nanoparticles considered.

Titanium dioxide is a sunscreen pigment with photocatalytic activity. We studied the behavior of different TiO2 specimens used in cosmetic products on the UVB-induced peroxidation of linoleic acid as model substrate and of porcine skin, at different pH values. Lipoperoxidation of linoleic acid occurred to a lower extent with the coated compared to the uncoated TiO2, and it decreased at pH 7.0 compared to 4.0. The addition of organic additives such as propylene glycol and ethanol induced a significant reduction of the lipoperoxidation activity, particularly with the most reactive TiO2 specimens. Similar results were obtained with the porcine skin.

Mt. Vesuvius, Italy, is regarded as one of the world's most dangerous volcanoes because of the potential for vast numbers of people to be affected by the renewal of volcanic activity; more than 600 000 people live within 10 km of the summit alone. Vesuvius has been quiescent since 1944 and with continued dormancy, the more likely it is that the next eruption will be explosive. At that point, wide-spread concern is likely over the potential health hazard of the ash, away from the zone of primary volcanic hazards. Analyses of the mineralogical and geochemical characteristics of ash provide us with critical information on the potential toxicity of the particles, for example, whether particles are sufficiently small to enter the lungs and whether the particles have reactive properties which could trigger disease. Rapid assessment of these characteristics allows real-time decision making on hazard mitigation issues (e.g. distribution of dust masks) and allows considered judgement on whether to embark on major medical/toxicological studies. The study presented here is the first time that the potential respiratory health hazard of ash from Vesuvius volcano has been considered and allows planning for future eruption scenarios. Twenty-one ash samples, representing the range of eruption styles at Vesuvius, were collected and analysed. The results demonstrate that the physical processes of fragmentation play an important role in determining the grain size and, therefore, hazard, of the ash. Here, the finest samples derive from the interaction of magma and water during the final, phreatomagmatic phases of plinian and subplinian eruptions (∼ 16 vol.%

Verticillium leptobactrum, a rare fungal species, has repeatedly been isolated from serpentinic rocks in the Western Alps, thus suggesting that it adapts easily to this selective mineral substrate. The rRNA internal transcribed spacer region of several isolates has been sequenced to confirm their identity and taxonomic position within Verticillium, a recently revised polyphyletic entity. Isolates of V. leptobactrum have also been investigated to establish their ability to weather asbestos chrysotile, the most common mineral in the isolation sites. The results of solubilization assays on magnesium and silicon, as well as measurement of the Mg/Si ratio in the asbestos fibres after exposure to fungal mycelia, indicate a high bioweathering activity of V. leptobactrum towards chrysotile. Comparison with data on Fusarium oxysporum shows differences among species, with V. leptobactrum being more active than F. oxysporum in removing structural ions from chrysotile. Asbestos weathering by fungi could be envisaged as a bioremediation strategy for hazardous asbestos-rich soils (e.g. abandoned mines). Fungi that have adapted to live in serpentine sites could be good candidates for this purpose.

Asbestos-cement roofs, the most widespread sources of airborne, toxic and carcinogenic asbestos fibres, are often colonized by lichens. Since these latter are physical and chemical weathering agents, they have been often considered as significant responsible of disaggregation processes increasing fibre dispersion. Consequently, official guidelines for the management of asbestos often suggest their removal. Weathering and/or covering effects of lichens on asbestos-cement, however, have never been deeply investigated and available procedures to evaluate asbestos-cement aging do not take the biological colonization into account. In this study we show that a 25% lichen cover modifies physical and chemical properties of asbestos-cement sheets containing chrysotile and crocidolite fibres. By innovatively coupling pull up tests and image analysis of linear structures, we show that fibre loss is significantly lower ( approximately 30%) where lichens develop and offer a physical barrier to the fibre detachment. Below the most covering lichens (Acarospora cervina, Candelariella ssp.), chrysotile and crocidolite undergo a partial incongruent dissolution, which in laboratory assays generally determined a reduction of their surface reactivity. Because of their biocovering and bioweathering effects, lichens on asbestos-cement play a role which differs from the current public opinion and the assumptions of some official regulations, acting as effective spontaneous bioattenuation agents.

The mechanisms underlying asbestos toxicity mainly rely on experiments performed on "laboratory" fibers, but little data is available on naturally occurring asbestos (NOA). Human exposure to NOA is subject to their ecopersistence and the modulation of their potential toxicity following weathering. The effect of weathering on three fibrous minerals from the Italian Western Alps, chrysotile, tremolite, and balangeroite-a Fe-rich asbestiform mineral-was investigated by mimicking more than 100 yr of physical (freezing-thawing/wetting-drying cycles in a climatic chamber) and biochemical forces (incubation with oxalic acid). Ion release, evaluated by means of inductively coupled plasma-atomic emission spectroscopy (ICP-AES), and variation in chemical composition, evaluated by scanning electron microscopy coupled with energy-dispersive spectroscopy (SEM-EDS), indicated that weathering modified the fibers in the series: chrysotilebalangeroitetremolite. Kinetics of ion release from the fibers (Mg, Fe, and Si) revealed different ion removal pathways. Tremolite was poorly affected. Chrysotile preferentially released cations up to a plateau, with physical and biochemical forces acting competitively. Conversely, for balangeroite, upon which weathering forces acted synergistically, the initial loss of ions facilitated further dissolution and more Si than Mg was released, suggesting an ongoing collapse of the crystal structure. Depletion of redox-reactive ions produced a significant reduction in fiber-derived *OH radicals (EPR, spin-trapping technique), but the fibrous nature was always retained. Despite weathered fibers appearing less toxic than "stored/laboratory" ones, NOA is to be considered far from safe because of fibrous nature and residual surface reactivity. Risk assessment needs to consider the effect of weathering on exposures. Both tremolite and balangeroite may contaminate, in some areas, chrysotile asbestos. However, in contrast to tremolite, balangeroite exhibits a low ecopersistence, similar to chrysotile behavior. Any contribution of balangeroite to chrysotile toxicity will thus be related to its quantitative occurrence and not to higher structural stability.

Indium-Tin-Oxide (ITO) is a sintered mixture of indium- (In(2)O(3)) and tin-oxide (SnO(2)) in a ratio of 90:10 (wt:wt) that is used for the manufacture of LCD screens and related high technology applications. Interstitial pulmonary diseases have recently been reported in workers from ITO producing plants. The present study was conducted to identify experimentally the exact chemical component responsible for this toxicity and to address possible mechanisms of action. The reactivity of respirable ITO particles was compared with that of its single components alone or their unsintered 90:10 mixture (MIX) both in vivo and in vitro. For all endpoints considered, ITO particles behaved as a specific toxic entity. In vivo, after a single pharyngeal administration (2-20 mg per rat), ITO particles induced a strong inflammatory reaction. At day 3, the inflammatory reaction (cell accumulation, LDH and protein in bronchoalveolar lavage fluid) appeared more marked with ITO particles than with each oxide separately or the MIX. This inflammatory reaction persisted and even worsened after 15 days. After 60 days, this inflammation was still present but no significant fibrotic response was observed. The cytotoxicity of ITO was assessed in vitro in lung epithelial cells (RLE) and macrophages (NR8383 cell line). While ITO particles (up to 200 microg/ml) did not affect epithelial cell integrity (LDH release), a strong cytotoxic response was found in macrophages exposed to ITO, but not to its components alone or mixed. ITO particles also induced an increased frequency of micronuclei in type II pneumocytes in vivo but not in RLE in vitro, suggesting the preponderance of a secondary genotoxic mechanism. To address the possible mechanism of ITO toxicity, reactive oxygen species production was assessed by electron paramagnetic resonance spectrometry in an acellular system. Carbon centered radicals (COO-.) and Fenton-like activity were detected in the presence of ITO particles, not with In(2)O(3), SnO(2) alone, or the MIX. Because the unsintered mixture of SnO(2) and In(2)O(3) particles was unable to reproduce the reactivity/toxicity of ITO particles, the sintering process through which SnO(2) molecules are introduced within the crystal structure of In(2)O(3) appears critical to explain the unique toxicological properties of ITO. The inflammatory and genotoxic activities of ITO dust indicate that a strict control of exposure is needed in industrial settings.

TiO(2) nanoparticles hazard is associated to their photocatalytic activity causing release of DNA damaging ROS (Reactive Oxygen Species), lipid peroxidation and skin damage. Various coatings have been proposed to minimize photocatalysis, while keeping the potential to block UV radiations. Uncoated and variously coated commercial nano-titania have been classified on the basis of UVB-induced lipoperoxidation of linoleic acid. A selection of the most and the least protective specimens was then examined by ESR (Electron Spin Resonance) to evidence the presence of surface paramagnetic centres and the release of ROS in aqueous suspensions (spin trapping). Paramagnetic centres and ROS were correlated with the extent of lipid peroxidation. When tested on porcine skin (mimicking the human one), titania acted as on linoleic acid. The combined use of lipid peroxidation of simple fatty acids with ESR analysis is here proposed as a possible screening tool for the evaluation of the potential toxicity of nano-titania in sunscreen preparations.

Iron-induced hydroxyl radical generation from the surface of volcanic ash particles is a possible mechanism of respiratory toxicity in addition to crystalline silica induced pathogenicity. Here we show that volcanic ash generates hydroxyl radicals, with greater reactivity in iron-rich, silica-poor samples, such as basaltic ash. Basaltic particles expose at the surface high levels of poorly-coordinated iron ions in both Fe(II) and Fe(III) oxidation states which are likely to be the cause of such reactivity. Hitherto, basaltic ash has been disregarded as a hazard due to the lack of crystalline silica particulate but future hazard assessment should consider its toxic potential.

Inhaled ultrafine particles show considerably stronger pulmonary inflammatory effects when tested at equal mass dose with their fine counterparts. However, the responsible mechanisms are not yet fully understood. We investigated the role of particle size and surface chemistry in initiating pro-inflammatory effects in vitro in A549 human lung epithelial cells on treatment with different model TiO(2) particles. Two samples of TiO(2), i.e. fine (40-300 nm) and ultrafine (20-80 nm) were tested in their native forms as well as upon surface methylation, as was confirmed by Fourier transformed infrared spectroscopy. Radical generation during cell treatment was determined by electron paramagnetic resonance with 5,5-dimethyl-1-pyrroline-N-oxide or 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl. Interleukin-8 mRNA expression/release was determined by RT-PCR and ELISA, whereas particle uptake was evaluated by transmission electron microscopy. TiO(2) particles were rapidly taken up by the cells, generally as membrane bound aggregates and large intracellular aggregates in vesicles, vacuoles and lamellar bodies. Aggregate size tended to be smaller for the ultrafine samples and was also smaller for methylated fine TiO(2) when compared to non-methylated fine TiO(2). No particles were observed inside nuclei or any other vital organelle. Both ultrafine TiO(2) samples but not their fine counterparts elicited significantly stronger oxidant generation and IL-8 release, despite their aggregation state and irrespective of their methylation. The present data indicate that ultrafine TiO(2), even as aggregates/agglomerates, can trigger inflammatory responses that appear to be driven by their large surface area. Furthermore, our results indicate that these effects result from oxidants generated during particle-cell interactions through a yet to be elucidated mechanism(s).

Sterile cultured isolates of lichen-forming ascomycetes have not yet been used to investigate mycobiont-mineral substrate interactions under controlled conditions. In this study Candelariella vitellina, Xanthoparmelia tinctina and Lecanora rupicola mycobionts were isolated and inoculated with chrysotile fibres in the laboratory, in order to verify whether physical and chemical weathering processes, which were already described in the field, may be reproduced in vitro. Tight adhesion of hyphae to chrysotile fibres was observed in all species. The adhering hyphae affected the chemical composition of asbestos fibres, with the selective depletion of magnesium being a prominent feature, as is the case in field conditions. Oxalic acid and pulvinic acid, mycobiont-derived metabolites of X. tinctina and C. vitellina, were involved in the weathering action. Time and environmental factors and the absence of biological synergisms strongly limited the chemical weathering in vitro compared with what was observed in the field. Nevertheless, the results show that in vitro incubation of sterile-cultured lichen-forming fungi with minerals is a practicable experimental system to investigate the weathering effects of different mycobionts and fungal compounds under controlled conditions.

Lunar dust toxicity has to be evaluated in view of future manned missions to the Moon. Previous studies on lunar specimens and simulated dusts have revealed an oxidant activity assigned to HO· release. However, the mechanisms behind the reactivity of lunar dust are still quite unclear at the molecular level. In the present study, a complementary set of tests--including terephthalate (TA) hydroxylation, free radical release as measured by means of the spin-trapping/electron paramagnetic resonance (EPR) technique, and cell-free lipoperoxidation--is proposed to investigate the reactions induced by the fine fraction of a lunar dust analogue (JSC-1A-vf) in biologically relevant experimental environments. Our study proved that JSC-1A-vf is able to hydroxylate TA also in anaerobic conditions, which indicates that molecular oxygen is not involved in such a reaction. Spin-trapping/EPR measures showed that the HO· radical is not the reactive intermediate involved in the oxidative potential of JSC-1A-vf. A surface reactivity implying a redox cycle of phosphate-complexed iron via a Fe(IV) state is proposed. The role of this iron species was investigated by assessing the reactivity of JSC-1A-vf toward hydrogen peroxide (Fenton-like activity), formate ions (homolytic rupture of C-H bond), and linoleic acid (cell-free lipoperoxidation). JSC-1A-vf was active in all tests, confirming that redox centers of transition metal ions on the surface of the dust may be responsible for dust reactivity and that the TA assay may be a useful field probe to monitor the surface oxidative potential of lunar dust.

In the course of studies of the interaction of proteins with TiO2 nanoparticles, we have investigated the role of the medium employed in cellular tests, by measuring the variation of ζ-potential vs pH in the range 2–9 and bovine serum albumin adsorption on TiO2 P25 in the presence of either HEPES or PBS as buffers, both mimicking the physiological pH, but with different chemical nature. The two buffers yield remarkably dissimilar surface charges and protein uptake, i.e., they impart different surface characteristics to the particles which could affect the contact with cells or tissues. This may account for dissimilar toxicological outcomes among in vitro tests and particularly between in vitro vs in vivo tests, considering the high amount of phosphate ions present in body fluids.

Some soil fungi growing on asbestos fibers release chelators and antioxidants. The bioweathering potential of fungi has thus been envisaged as a possible route for bioremediation of asbestos rich soils, where no inactivation procedures have been established so far. The present study reports fungal-mediated modification of the surface reactivity of the fibers and of their potential to damage DNA in vitro. Verticillium sp. and Paecilomyces sp. were selected among the fungi isolated from fragments of chrysotile bearing rocks, as the most potent in iron extraction, and studied in parallel with F. oxysporum, previously reported to modify the surface reactivity of asbestos fibers. One sample of chrysotile from the Western Alps and a sample of UICC (Union Internationale Contre le Cancer) crocidolite were incubated with or without fungi. All fungi extracted iron from both fibers (7.3% from crocidolite and 33.6% from chrysotile by Verticillium sp.), releasing it into the medium. F. oxysporum and Paecilomyces sp. suppressed the potential of the fibers to release hydroxyl radical, while Verticillium sp. suppressed it on crocidolite but enhanced it on chrysotile, a hallmark of ongoing mobilization of reactive iron. Fibers incubated in the growth medium, but in the absence of fungi, exhibited a remarkable potential to damage DNA in vitro, measured by the generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, while all the fungi reduced such effect. Fungi may thus be regarded as appropriate candidates for bioremediation of asbestos rich soils whereby the reactive iron ions responsible for DNA damage are progressively removed from the fibers.

Carbon nanotubes (CNTs) currently attract intense research efforts because of their unique properties which make them suitable for many industrial applications. When inhaled, CNTs constitute a possible hazard to human health. Several studies have shown that when instilled in the lung of experimental animals, CNTs induced an inflammatory and fibrotic response similar to that caused by other toxic particles which might be the result of oxidative stress caused by particle- and/or cell-derived free radicals. There is, however, no direct experimental evidence of a capacity of carbon nanotubes to generate directly free radicals. Here we report that multiwall carbon nanotubes (MWCNT) in aqueous suspension do not generate oxygen or carbon-centered free radicals in the presence of H2O2 or formate, respectively, as detected with the spin-trapping technique. Conversely, we observed that, when in contact with an external source of hydroxyl or superoxide radicals, MWCNT exhibit a remarkable radical scavenging capacity. It is therefore possible that the inflammatory reaction reported in vivo must be ascribed to MWCNT features other than particle-derived free radical generation.

This working group report is the product of the joint efforts of the members of an expert working group organized and convened by the International Life Sciences Institute Risk Science Institute. A...

Background: The hypothesis of widely differing lung damage due to commonly used types of quartz was studied in 16 samples of respirable quartzes (>99% silica) from sites of the European quartz industry, using an in vitro test, the vector model. Two samples with high and 2 with low biological activities were identified and subsequently examined for their in vivo lung toxicity (inflammation, fibrosis, genotoxicity) and surface characteristics. Alveolar macrophages (AM) are considered the target cells of primary dust effects. The vector model mimics some of the elemental dust cell effects such as cell toxicity, effects on the metabolism and stimulatory effects, e.g., TNF alpha and dust-induced ROS secretion. Methods: Doses of 15, 30, 60 and 120μg dust per 106 AM were used together with the control dusts (quartz DQ12 and corundum). Testing parameters were LDH, glucuronidase, PMA forced ROS release, TNF alpha and dust induced ROS secretion. The main criterion for the selection of low or high activity samples was the secretion of TNF alpha. Results: (i) Apart from quartz samples with an activity close to that of DQ12, one also finds examples with a very low activity. (ii) In comparison particular parameters are linked with a specific dose response relationship and different dose points for the leveling off of the effects. The levels of TNF alpha represent a conspicuously broad response pattern; some samples induce secretion at the lowest dose and others are not active even at the highest dose investigated at already apparent toxicity. (iii) Regarding various parameters the dust samples led to distinct dose response profiles considered as vectors. The current study indicates that within the particle type “quartz fine dust” varying harmful doses and different elements of damage must be present. (iv) The lung damage of the subchronic animal assay coincides with in vitro tests thus confirming the concept of the vector model. Conclusion: Threshold effects in the range of 15 – ≥120μg can be demonstrated for the discriminant vector TNF alpha, i.e. over 4 steps of dose doubling. These studies show very toxic quartzes but also quartzes of low biological activity comparable to corundum.

Exposure to particulate silica (most crystalline polymorphs) causes a persistent inflammation sustained by the release of oxidants in the alveolar space. Reactive oxygen species (ROS), which include hydroxyl radical, superoxide anion, hydrogen peroxide, and singlet oxygen, are generated not only at the particle surface, but also by phagocytic cells attempting to digest the silica particle. Two distinct kinds of surface centers-silica-based surface radicals and poorly coordinated iron ions-generate O(2)(*)(-) and HO(*) in aqueous solution via different mechanisms. Crystalline silica is also a potent stimulant of the respiratory burst in phagocytic cells with increased oxygen consumption and production of O(*)(-), H(2)O(2), and NO leading to acute inflammation and HO(*) generation in the lung. Oxidative stress elicited by crystalline silica is also evidenced by increased expression of antioxidant enzymes such as manganese superoxide dismutase (Mn-SOD) and glutathione peroxidase, and the enzyme inducible nitric oxide synthase (iNOS). Generation of oxidants by crystalline silica particles and by silica-activated cells results in cell and lung injury, activation of cell signaling pathways to include MAPK/ERK kinase (MEK), and extracellular signal-regulated kinase (ERK) phosphorylation, increased expression of inflammatory cytokines (e.g., tumor necrosis factoralpha [TNFalpha], interleukin-1 [IL-1]), and activation of specific transcription factors (e.g., NFkappaB, AP-1). Silica can also initiate apoptosis in response to oxygen- and nitrogen-based free radicals, leading to mitochondrial dysfunction, increased gene expression of death receptors, and/or their ligands (TNFalpha, Fas ligand [FasL]).