Crystalline Phase Modulates the Potency of Nanometric TiO₂ to Adhere to and Perturb the Stratum Corneum of Porcine Skin under Indoor Light

Nanometric TiO₂ is largely employed in cosmetics, but in vitro toxic effects have been reported when nano-TiO₂ is exposed to UV light. The photoreactivity of TiO₂ largely depends on its crystal phase, namely, anatase and rutile. Surface acidity, which is also dependent on crystal structure, may impart a positive or negative charge to the nanomaterial surface and ultimately modulate particle adhesion to tissues. Three nanometric TiO₂ powders with a different crystal lattice and surface charge (anatase, rutile, and anatase/rutile) have been employed here to investigate their interaction with the skin and to examine the molecular mechanisms of the TiO₂-induced oxidative damage. The strength of the interaction of nano-TiO₂ with skin has been revealed by chemiometric mapping (μ-XRF and SEM–EDS) after tissue washing. Positively charged anatase and anatase/rutile, but not negatively charged rutile, were strongly held on the skin surface and were able to promote a structural rearrangement of the lipid bilayer in the stratum corneum (DSC and Raman) under controlled indoor illumination (UVA < 1 mW/m²). Under the same conditions, cell-free reactivity tests (ROS-mediated free-radical release and lipoperoxidation) indicated that anatase and anatase/rutile are more reactive than rutile, suggesting a ROS-mediated oxidative mechanism that may alter the structure of the stratum corneum. Both the higher oxidative potential and the stronger adhesion to skin of anatase and anatase/rutile TiO₂ may explain the stronger disorganization induced by these two samples and suggests the use of rutile to produce safer TiO₂-based cosmetic and pharmaceutical products

In Search of the Chemical Basis of the Hemolytic Potential of Silicas

The membranolytic activity of silica particles toward red blood cells (RBCs) has been known for a long time and is sometimes associated with silica pathogenicity. However, the molecular mechanism and the reasons why hemolysis differs according to the silica form are still obscure. A panel of 15 crystalline (pure and commercial) and amorphous (pyrogenic, precipitated from aqueous solutions, vitreous) silica samples differing in size, origin, morphology, and surface chemical composition were selected and specifically prepared. Silica particles were grouped into six groups to compare their potential in disrupting RBC membranes so that one single property differed in each group, while other features were constant. Free radical production and crystallinity were not strict determinants of hemolytic activity. Particle curvature and morphology modulated the hemolytic effect, but silanols and siloxane bridges at the surface were the main actors. Hemolysis was unrelated to the overall concentration of silanols as fully rehydrated surfaces (such as those obtained from aqueous solution) were inert, and one pyrogenic silica also lost its membranolytic potential upon progressive dehydration. Overall results are consistent with a model whereby hemolysis is determined by a defined surface distribution of dissociated/undissociated silanols and siloxane groups strongly interacting with specific epitopes on the RBC membrane

Hematite Nanoparticles Larger than 90 nm Show No Sign of Toxicity in Terms of Lactate Dehydrogenase Release, Nitric Oxide Generation, Apoptosis, and Comet Assay in Murine Alveolar Macrophages and Human Lung Epithelial Cells

Three hematite samples were synthesized by precipitation from a FeCl₃ solution under controlled pH and temperature conditions in different morphology and dimensions: (i) microsized (average diameter 1.2 μm); (ii) submicrosized (250 nm); and (iii) nanosized (90 nm). To gain insight into reactions potentially occurring <i>in vivo</i> at the particle–lung interface following dust inhalation, several physicochemical features relevant to pathogenicity were measured (free radical generation in cell-free tests, metal release, and antioxidant depletion), and cellular toxicity assays on human lung epithelial cells (A549) and murine alveolar macrophages (MH-S) were carried out (LDH release, apoptosis detection, DNA damage, and nitric oxide synthesis). The decrease in particles size, from 1.2 μm to 90 nm, only caused a slight increase in structural defects (disorder of the hematite phase and the presence of surface ferrous ions) without enhancing surface reactivity or cellular responses in the concentration range between 20 and 100 μg cm^–2

Additional file 1: Figure S1. of Revisiting the paradigm of silica pathogenicity with synthetic quartz crystals: the role of crystallinity and surface disorder

Particle size distribution curves of the quartz crystals studied measured with DCS technique. Figure S2. Bio-TEM images of quartz samples internalized by RAW 264.7 murine macrophages. Figure S3. Size characterization curve of liposome dispersion measured by DLS. Table S1. Curve-fit parameters calculated by fitting experimental dataset (Μ potential vs pH) with a Boltzmann equation. (DOCX 952 kb

Surface Reactivity and Cell Responses to Chrysotile Asbestos Nanofibers

High aspect-ratio nanomaterials (HARNs) have recently attracted great attention from nanotoxicologists because of their similarity to asbestos. However, the actual risk associated with the exposure to nanosized asbestos, which escapes most regulations worldwide, is still unknown. Nanometric fibers of chrysotile asbestos have been prepared from two natural sources to investigate whether nanosize may modulate asbestos toxicity and gain insight on the hazard posed by naturally occurring asbestos, which may be defined as HARNs because of their dimensions. Power ultrasound was used to obtain nanofibers from two different chrysotile specimens, one from the dismissed asbestos mine in Balangero (Italian Western Alps) and the other from a serpentine outcrop in the Italian Central Alps. Electron microscopy, X-ray diffraction, and fluorescence spectroscopy revealed that the procedure does not affect mineralogical and chemical composition. Surface reactions related to oxidative stress, free radical generation, bioavailability of iron, and antioxidant depletion, revealed a consistent reduction in reactivity upon reduction in size. When tested on A549 human epithelial cells, the pristine but not the nanosized fibers proved cytotoxic (LDH release), induced NO production, and caused lipid peroxidation. However, nanofibers still induced some toxicity relevant oxidative stress activity (ROS production) in a dose-dependent fashion. The reduction in length and a lack of poorly coordinated bioavailable iron in nanochrysotile may explain this behavior. The present study provides a one-step procedure for the preparation of a homogeneous batch of natural asbestos nanofibers and shows how a well-known toxic material might not necessarily become more toxic than its micrometric counterpart when reduced to the nanoscale

Evaluating the mechanistic evidence and key data gaps in assessing the potential carcinogenicity of carbon nanotubes and nanofibers in humans

<p>In an evaluation of carbon nanotubes (CNTs) for the IARC Monograph 111, the Mechanisms Subgroup was tasked with assessing the strength of evidence on the potential carcinogenicity of CNTs in humans. The mechanistic evidence was considered to be not strong enough to alter the evaluations based on the animal data. In this paper, we provide an extended, in-depth examination of the <i>in vivo</i> and <i>in vitro</i> experimental studies according to current hypotheses on the carcinogenicity of inhaled particles and fibers. We cite additional studies of CNTs that were not available at the time of the IARC meeting in October 2014, and extend our evaluation to include carbon nanofibers (CNFs). Finally, we identify key data gaps and suggest research needs to reduce uncertainty. The focus of this review is on the cancer risk to workers exposed to airborne CNT or CNF during the production and use of these materials. The findings of this review, in general, affirm those of the original evaluation on the inadequate or limited evidence of carcinogenicity for most types of CNTs and CNFs at this time, and possible carcinogenicity of one type of CNT (MWCNT-7). The key evidence gaps to be filled by research include: investigation of possible associations between <i>in vitro</i> and early-stage <i>in vivo</i> events that may be predictive of lung cancer or mesothelioma, and systematic analysis of dose–response relationships across materials, including evaluation of the influence of physico-chemical properties and experimental factors on the observation of nonmalignant and malignant endpoints.</p