Open Access

Aluminum has gathered toxicological Attention based on relevant human exposure and its suspected hazardous potential. Nanoparticles from food supplements or Food contact materials may reach the human gastrointestinal tract. Here, we monitored the physicochemical fate of aluminum containing nanoparticles and aluminum ions when passaging an in vitro model of the human gastrointestinal tract. Smallangle X-ray scattering (SAXS), transmission electron microscopy (TEM), ion beam microscopy (IBM), secondary ion beam mass spectrometry (TOF-SIMS), and inductively coupled plasma mass spectrometry (ICP-MS) in the singleparticle mode were employed to characterize two aluminumcontaining nanomaterials with different particle core materials (Al0, γAl2O3) and soluble AlCl3. Particle size and shape remained unchanged in saliva, whereas strong Agglomeration of both aluminum nanoparticle species was observed at low pH in gastric fluid together with an increased ion release. The levels of free aluminum ions decreased in intestinal fluid and the particles deagglomerated, thus liberating primary particles again. Dissolution of nanoparticles was limited and substantial changes of their shape and size were not detected. The amounts of particle-associated phosphorus, chlorine, potassium, and calcium increased in intestinal fluid, as compared to nanoparticles in standard dispersion. Interestingly, nanoparticles were found in the intestinal fluid after addition of ionic aluminum. We provide a comprehensive characterization of the fate of aluminum nanoparticles in simulated gastrointestinal fluids, demonstrating that orally ingested nanoparticles probably reach the intestinal epithelium. The balance between dissolution and de novo complex formation should be considered when evaluating nanotoxicological experiments.

Aluminum (Al) is one of the most common elements in the earth crust and increasingly used in food, consumer products and packaging. Its hazard potential for humans is still not completely understood. Besides the metallic form, Al also exists as mineral, including the insoluble oxide, and in soluble ionic forms. Representatives of these three species, namely a metallic and an oxidic species of Al-containing nanoparticles and soluble aluminum chloride, were applied to human intestinal cell lines as models for the intestinal barrier. We characterized physicochemical particle parameters, protein corona composition, ion release and cellular uptake. Different in vitro assays were performed to determine potential effects and molecular modes of Action related to the individual chemical species. For a deeper insight into signaling processes, microarray transcriptome analyses followed by bioinformatic data analysis were employed. The particulate Al species showed different solubility in biological media. Metallic Al nanoparticles released more ions than Al2O3 nanoparticles, while AlCl3 showed a mixture of dissolved and agglomerated particulate entities in biological media. The protein corona composition differed between both nanoparticle species. Cellular uptake, investigated in transwell experiments, occurred predominantly in particulate form, whereas ionic Al was not taken up by intestinal cell lines. Transcellular transport was not observed. None of the Al species showed cytotoxic effects up to 200 mg Al/mL. The transcriptome analysis indicated mainly effects on oxidative stress pathways, xenobiotic metabolism and metal homeostasis. We have shown for the first time that intestinal cellular uptake of Al occurs preferably in the particle form, while toxicological effects appear to be ion-related.

In a long-term research strategy, the German higher federal authorities responsible for human and environmental safety – the German Environment Agency (UBA), the Federal Institute for Risk Assessment (BfR), the Federal Institute for Occupational Safety and Health (BAuA), the Federal Institute for Materials Research and Testing (BAM) and the National Metrology Institute (PTB) – are accompanying the rapid pace of development of new materials from the points of view of occupational safety and health, consumer protection and environmental protection. The strategy is therefore closely linked with public funding programmes for research on nanomaterials and other advanced materials, such as those of the Federal Ministry of Education and Research (BMBF) (“From Material to Innovation”) and the EU (“Horizon 2020”). The research strategy builds on the outcomes so far of the joint research strategy of the higher federal authorities launched in 2008 and first evaluated in 2013, “Nanotechnology: Health and Environmental Risks of Nanomaterials”, while additionally covering other advanced materials where these pose similar risks to humans and the environment or where such risks need to be studied. It also takes up the idea of application safety of chemical products from the New Quality of Work (INQA) initiative of the Federal Ministry of Labour and Social Affairs (BMAS) and the concept of sustainable chemistry endorsed by the Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety (BMUB). Application safety and environmental compatibility are aimed for advanced materials and derived products in order to largely rule out unacceptable risks to humans and the environment. This can be achieved by: 1. Using safe materials without hazardous properties for humans and the environment direct application safety); or 2. Product design for low emissions and environmental compatibility over the entire product lifecycle (integrated application safety); or 3. Product stewardship, where producers support users in taking technical, organisational and personal safety measures for the safe use and disposal of products (supported application safety). As a comprising part of the Federal Government’s Nanotechnology Action Plan 2020, the update of the joint research strategy aims to contribute to governmental research in the following main areas: • Characterising and assessing the human and environmental risks of advanced materials • Supporting research institutions and business enterprises • Science-based revision of legal requirements and recommendations • Public acceptance The research strategy is to be implemented in projects and other research-related activities. These include governmental research, tendering and extramural research funding, and participation in mostly publicly supported projects with third-party funding. Additional activities will take place as part of policy advice and the ongoing work of the sovereign tasks of agencies involved. Interdisciplinary and transdisciplinary approaches will be used to better connect risk and safety research with innovation research and material development. In keeping up with the rapid pace of development, the time horizon for the research strategy is up to 2020. The research objectives address the research approaches likely to be actionable in this period. The research strategy will be supported by a working group and be evaluated and revised by the end of the Nanotechnology Action Plan 2020.

Recent DNA-based studies have shown that the built environment is surprisingly rich in fungi. These indoor fungi – whether transient visitors or more persistent residents – may hold clues to the rising levels of human allergies and other medical and building-related health problems observed globally. The taxo¬nomic identity of these fungi is crucial in such pursuits. Molecular identification of the built mycobiome is no trivial undertaking, however, given the large number of unidentified, misidentified, and technically compromised fungal sequences in public sequence databases. In addition, the sequence metadata required to make informed taxonomic decisions – such as country and host/substrate of collection – are often lacking even from reference and ex-type sequences. Here we report on a taxonomic annotation workshop (April 10–11, 2017) organized at the James Hutton Institute/University of Aberdeen (UK) to facilitate reproducible studies of the built mycobiome. The 32 participants went through public fungal ITS bar¬code sequences related to the built mycobiome for taxonomic and nomenclatural correctness, technical quality, and metadata availability. A total of 19,508 changes – including 4,783 name changes, 14,121 metadata annotations, and the removal of 99 technically compromised sequences – were implemented in the UNITE database for molecular identification of fungi (https://unite.ut.ee/) and shared with a range of other databases and downstream resources. Among the genera that saw the largest number of changes were Penicillium, Talaromyces, Cladosporium, Acremonium, and Alternaria, all of them of significant importance in both culture-based and culture-independent surveys of the built environment.

Size and shape are crucial parameters which have impact on the potential of nanoparticles to penetrate cell membranes and epithelial barriers. Current research in nanotoxicology additionally focuses on particle coating. To distinguish between core- and coating-related effects in nanoparticle uptake and translocation, two nanoparticles equal in size, coating and charge but different in core material were investigated. Silver and iron oxide nanoparticles coated with poly(acrylic acid) were chosen and extensively characterized by small-angle x-ray scattering, nanoparticle tracing analysis and transmission electron microscopy (TEM). Uptake and transport were studied in the intestinal Caco-2 model in a Transwell System with subsequent elemental analysis. TEM and ion beam microscopy were conducted for particle visualization. Although equal in size, charge and coating, the behavior of the two particles in Caco-2 cells was different: while the internalized amount was comparable, only iron oxide nanoparticles additionally passed the epithelium. Our findings suggest that the coating material influenced only the uptake of the nanoparticles whereas the translocation was determined by the core material. Knowledge about the different roles of the particle coating and core materials in crossing biological barriers will facilitate toxicological risk assessment of nanoparticles and contribute to the optimization of pharmacokinetic properties of nano-scaled pharmaceuticals.