The complex puzzle of dietary silver nanoparticles, mucus and microbiota in the gut.

Hundreds of consumer and commercial products containing silver nanoparticles (AgNPs) are currently used in food, personal-care products, pharmaceutical, and many other applications. Human exposure to AgNPs includes oral intake, inhalation, and dermal contact. The aim of this review was to focus on oral intake, intentional and incidental of AgNPs where well-known antimicrobial characteristics that might affect the microbiome and mucus in the gastrointestinal tract (GIT). This critical review summarizes what is known regarding the impacts of AgNPs on gut homeostasis. It is fundamental to understand the forms of AgNPs and their physicochemical characterization before and during digestion. For example, lab-synthesized AgNPs differ from "real" ingestable AgNPs used as food additives and dietary supplements. Similarly, the gut environment alters the chemical and physical state of Ag that is ingested as AgNPs. Emerging research on in vitro and in vivo rodent and human indicated complex multi-directional relationships among AgNPs, the intestinal microbiota, and the epithelial mucus. It may be necessary to go beyond today's descriptive approach to a modeling-based ecosystem approach that might quantitatively integrate spatio-temporal interactions among microbial groups, host factors (e.g., mucus), and environmental factors, including lifestyle-based stressors. It is suggested that future research (1) utilize more representative AgNPs, focus on microbe/mucus interactions, (2) assess the effects of environmental stressors for longer and longitudinal conditions, and (3) be integrated using quantitative modeling.

Relative potency factor approach enables the use of in vitro information for estimation of human effect factors for nanoparticle toxicity in life-cycle impact assessment.

The major theme of the NRC report "Toxicity Testing in the Twenty-first Century" is to replace animal testing by using alternative in vitro methods. Therefore, it can be expected that in the future in vivo data will be replaced with in vitro data. Hence, there is a need for new strategies to make use of the increasing amount of in vitro data when developing human toxicological effect factors (HEF) to characterize the impact category of human toxicity in life cycle assessment (LCA). Here, we present a new approach for deriving HEF for manufactured nanomaterials (MNMs) based on the combined use of in vitro toxicity data and a relative potency factor (RPF) approach. In vitro toxicity tests with nano-CuO, nano-Ag and nano-ZnO and their corresponding ions were performed on THP-1, CaCo-2 and Hep-G2 cell lines. The ratio of the here calculated EC50 of the ionic form and the nanoform corresponds to the Relative Potency Factor (RPF). Using this approach, HEFs (case/kgintake) for the aforementioned nanoparticles were obtained. Non-carcinogenic HEFs (case/kgintake) for exposure via ingestion of 5.9E-01, 7.5E-03 and 2.5 E-02 were calculated for nano-Ag, nano-CuO and nano-ZnO, respectively. The HEF values here proposed were compared with HEF values extrapolated from in vivo toxicity data reported in the literature. The here presented procedure is the most appropriate approximation currently available for using in vitro toxicity data on MNM for application in the field of LCIA.

In vitro toxicity assessment of emitted materials collected during the manufacture of water pipe plastic linings.

Objectives: US water infrastructure is in need of widespread repair due to age-related deterioration. Currently, the cured-in-place (CIPP) procedure is the most common method for water pipe repair. This method involves the on-site manufacture of a new polymer composite plastic liner within the damaged pipe. The CIPP process can release materials resulting in occupational and public health concerns. To understand hazards associated with CIPP-related emission exposures, an in vitro toxicity assessment was performed. Materials and Methods: Mouse alveolar epithelial and alveolar macrophage cell lines and condensates collected at 3 worksites utilizing styrene-based resins were utilized for evaluations. All condensate samples were normalized based on the major emission component, styrene. Further, a styrene-only exposure group was used as a control to determine mixture related toxicity. Results: Cytotoxicity differences were observed between worksite samples, with the CIPP worksite 4 sample inducing the most cell death. A proteomic evaluation was performed, which demonstrated styrene-, worksite-, and cell-specific alterations. This examination of protein expression changes determined potential biomarkers of exposure including transglutaminase 2, advillin, collagen type 1, perilipin-2, and others. Pathway analysis of exposure-induced proteomic alterations identified MYC and p53 to be regulators of cellular responses. Protein changes were also related to pathways involved in cell damage, immune response, and cancer. Conclusions: Together these findings demonstrate potential risks associated with the CIPP procedure as well as variations between worksites regarding emissions and toxicity. Our evaluation identified biological pathways that require a future evaluation and also demonstrates that exposure assessment of CIPP worksites should examine multiple chemical components beyond styrene, as many cellular responses were styrene-independent.

Introducing a new standardized nanomaterial environmental toxicity screening testing procedure, ISO/TS 20787: aquatic toxicity assessment of manufactured nanomaterials in saltwater Lakes using Artemia sp. nauplii.

This paper introduces a new standardized testing procedure for nanomaterial environmental toxicity (International Organization for Standardization/Technical Specification (ISO/TS) 20787): 'aquatic toxicity assessment of manufactured nanomaterials in saltwater lakes using Artemia sp. Nauplii' intended to generate more reliable and repeatable aquatic toxicity data testing manufactured nanomaterials, using Artemia sp., to evaluate their possible ecotoxicity in saltwater lake ecosystems. The principles behind testing with Artemia sp. are reviewed and the paper gives an overview of research published between 2009 and 2018 in which manufactured nanomaterials were tested using Artemia sp.

Organ-on-a-chip for assessing environmental toxicants.

Man-made xenobiotics, whose potential toxicological effects are not fully understood, are oversaturating the already-contaminated environment. Due to the rate of toxicant accumulation, unmanaged disposal, and unknown adverse effects to the environment and the human population, there is a crucial need to screen for environmental toxicants. Animal models and in vitro models are ineffective models in predicting in vivo responses due to inter-species difference and/or lack of physiologically-relevant 3D tissue environment. Such conventional screening assays possess limitations that prevent dynamic understanding of toxicants and their metabolites produced in the human body. Organ-on-a-chip systems can recapitulate in vivo like environment and subsequently in vivo like responses generating a realistic mock-up of human organs of interest, which can potentially provide human physiology-relevant models for studying environmental toxicology. Feasibility, tunability, and low-maintenance features of organ-on-chips can also make possible to construct an interconnected network of multiple-organs-on-chip toward a realistic human-on-a-chip system. Such interconnected organ-on-a-chip network can be efficiently utilized for toxicological studies by enabling the study of metabolism, collective response, and fate of toxicants through its journey in the human body. Further advancements can address the challenges of this technology, which potentiates high predictive power for environmental toxicology studies.

Demonstration of a modelling-based multi-criteria decision analysis procedure for prioritisation of occupational risks from manufactured nanomaterials.

Several tools to facilitate the risk assessment and management of manufactured nanomaterials (MN) have been developed. Most of them require input data on physicochemical properties, toxicity and scenario-specific exposure information. However, such data are yet not readily available, and tools that can handle data gaps in a structured way to ensure transparent risk analysis for industrial and regulatory decision making are needed. This paper proposes such a quantitative risk prioritisation tool, based on a multi-criteria decision analysis algorithm, which combines advanced exposure and dose-response modelling to calculate margins of exposure (MoE) for a number of MN in order to rank their occupational risks. We demonstrated the tool in a number of workplace exposure scenarios (ES) involving the production and handling of nanoscale titanium dioxide, zinc oxide (ZnO), silver and multi-walled carbon nanotubes. The results of this application demonstrated that bag/bin filling, manual un/loading and dumping of large amounts of dry powders led to high emissions, which resulted in high risk associated with these ES. The ZnO MN revealed considerable hazard potential in vivo, which significantly influenced the risk prioritisation results. In order to study how variations in the input data affect our results, we performed probabilistic Monte Carlo sensitivity/uncertainty analysis, which demonstrated that the performance of the proposed model is stable against changes in the exposure and hazard input variables.

Cellular effects of manufactured nanoparticles: effect of adsorption ability of nanoparticles.

Nanoparticles are important industrial materials. However, many nanoparticles show biological effects, including toxic activity. Metal ion release is the most important factor affecting the biological effects of nanoparticles. In addition, nanoparticles have large adsorption ability. The adsorption ability, in particular protein adsorption to nanoparticles, has an effect on cellular uptake and cellular metabolisms. Moreover, the adsorption ability of nanoparticles causes artificial effects in in vitro systems. Consequently, accurate determination of released or secreted proteins such as lactate dehydrogenase and cytokines adsorbed to nanoparticles is affected. In addition, artificial effects cause overestimation or underestimation of the cytotoxicity of nanoparticles. Therefore, measurement of the protein adsorption of nanoparticles is important. Some methods for the determination of the adsorption to nanoparticles have been suggested. The flow field-flow fractionation method is one of the efficient techniques for determining proteins on the surface of nanoparticles. The cellular effects caused by nanoparticles should be carefully considered.

Ecotoxicity of manufactured ZnO nanoparticles--a review.

This report presents an exhaustive literature review on the toxicity of manufactured ZnO nanoparticles (NPs) to ecological receptors across different taxa: bacteria, algae and plants, aquatic and terrestrial invertebrates and vertebrates. Ecotoxicity studies on ZnO NPs are most abundant in bacteria, and are relatively lacking in other species. These studies suggest relative high acute toxicity of ZnO NPs (in the low mg/l levels) to environmental species, although this toxicity is highly dependent on test species, physico-chemical properties of the material, and test methods. Particle dissolution to ionic zinc and particle-induced generation of reactive oxygen species (ROS) represent the primary modes of action for ZnO NP toxicity across all species tested, and photo-induced toxicity associated with its photocatalytic property may be another important mechanism of toxicity under environmentally relevant UV radiation. Finally, current knowledge gaps within this area are briefly discussed and recommendations for future research are made.

Man-made mineral fibers and the respiratory tract.

Man-made mineral fibers are produced using inorganic materials and are widely used as thermal and acoustic insulation. These basically include continuous fiberglass filaments, glass wool (fiberglass insulation), stone wool, slag wool and refractory ceramic fibers. Likewise, in the last two decades nanoscale fibers have also been developed, among these being carbon nanotubes with their high electrical conductivity, mechanical resistance and thermal stability. Both man-made mineral fibers and carbon nanotubes have properties that make them inhalable and potentially harmful, which have led to studies to assess their pathogenicity. The aim of this review is to analyze the knowledge that currently exists about the ability of these fibers to produce respiratory diseases.

Ecotoxicity test methods for engineered nanomaterials: practical experiences and recommendations from the bench.

Ecotoxicology research is using many methods for engineered nanomaterials (ENMs), but the collective experience from researchers has not been documented. This paper reports the practical issues for working with ENMs and suggests nano-specific modifications to protocols. The review considers generic practical issues, as well as specific issues for aquatic tests, marine grazers, soil organisms, and bioaccumulation studies. Current procedures for cleaning glassware are adequate, but electrodes are problematic. The maintenance of exposure concentration is challenging, but can be achieved with some ENMs. The need to characterize the media during experiments is identified, but rapid analytical methods are not available to do this. The use of sonication and natural/synthetic dispersants are discussed. Nano-specific biological endpoints may be developed for a tiered monitoring scheme to diagnose ENM exposure or effect. A case study of the algal growth test highlights many small deviations in current regulatory test protocols that are allowed (shaking, lighting, mixing methods), but these should be standardized for ENMs. Invertebrate (Daphnia) tests should account for mechanical toxicity of ENMs. Fish tests should consider semistatic exposure to minimize wastewater and animal husbandry. The inclusion of a benthic test is recommended for the base set of ecotoxicity tests with ENMs. The sensitivity of soil tests needs to be increased for ENMs and shortened for logistics reasons; improvements include using Caenorhabditis elegans, aquatic media, and metabolism endpoints in the plant growth tests. The existing bioaccumulation tests are conceptually flawed and require considerable modification, or a new test, to work for ENMs. Overall, most methodologies need some amendments, and recommendations are made to assist researchers.

[Contemporary aspects of maintenance and promotion of health of the workers employed at the aluminum production enterprises].

The exposure of the combined occupational hazards on the workers of aluminum plants results in the development of the occupational chronic diseases of bronchopulmonary and bone systems and oncopathology. Pathogenetic mechanisms of the toxic exposure of fluorides on the body as well as molecular and cellular structures are presented.

[Emerging issues concerning hygiene in the Russian aluminum industry].

In this study the data of multiyear investigations of occupational and environmental hazards at different enterprises of the Russian aluminum industry are presented. Basing on these data, we have been elaborated the algorithm and methodological approaches on management of the occupational and ecology-related risks using hygienic safety criteria, risk evaluation technique, epidemiological and economic analysis.

[Issues of occupational health in the aluminium plant with superpower equipment].

Purpose of the research is to provide a hygienic assessment of working conditions at aluminum plants equipped with Central working prebaked (CWPB) cells operating at currents of 330 kA. The studies have indicated that the leading occupational exposures, the levels of which exceed the national standards, are: fluorine compound in the air of work area; unfavorable microclimate, constant magnetic field, the severity of the labour. According to the general hygienic assessment, with account of combined influence harmful occupational factors, the working conditions are attributed to 1-2 degrees of the 3 class of harmful working conditions, that conform to the small (moderate) and significant occupational risk.

[Heath status and level of adaptation in workers of the aluminium industry and technologies of the restorative medicine].

The results of the research of states of adaptation and health in workers of the aluminum industry are provided. Functional connection of the level of adaptability in respect of the parameter of adaptation (AP) with the length of employment has been revealed. The technologies of rehabilitative treatment under the conditions of the chronic fluoric intoxication have been presented.

On the lifecycle of nanocomposites: comparing released fragments and their in-vivo hazards from three release mechanisms and four nanocomposites.

Nanocomposites are the dominating class of nanomaterials to come into consumer contact, and were in general assumed to pose low risk. The first data is now emerging on the exposure from nanocomposites, but little is yet known about their hypothetical nanospecific physiological effects, giving ample room for speculation. For the first time, this comprehensive study addresses these aspects in a systematic series of thermoplastic and cementitious nanocomposite materials. Earlier reports that 'chalking', the release of pigments from weathered paints, also occurs for nanocomposites, are confirmed. In contrast, mechanical forces by normal consumer use or do-it-yourself sanding do not disrupt nanofillers (nanoparticles or nanofibers) from the matrix. Detailed evidence is provided for the nature of the degradation products: no free nanofillers are detected up to the detection threshold of 100 ppm. Sanding powders measuring 1 to 80 µm in diameter are identified with the original material, still containing the nanofillers. The potential hazard from aerosols generated by sanding nanocomposites up to the nuisance dust limit is also investigated. In-vivo instillation in rats is used to quantify physiological effects on degradation products from abraded nanocomposites, in comparison to the abraded matrix without nanofiller and to the pure nanofiller. In this pioneering and preliminary evaluation, the hazards cannot be distinguished with or without nanofiller.

Phytotoxicity of silver nanoparticles to Lemna minor L.

The use of silver nanoparticles (AgNPs) in commercial products has increased significantly in recent years. Although there has been some attempt to determine the toxic effects of AgNPs, there is little information on aquatic plants which have a vital role in ecosystems. This study reports the use of Lemna minor L. clone St to investigate the phytotoxicity of AgNPs under modified OECD test conditions. AgNPs were synthesised, characterised and subsequently presented to the L. minor. Results showed that inhibition of plant growth was evident after exposure to small (~ 20 nm) and larger (~100 nm) AgNPs at low concentrations (5 µg L⁻¹) and this effect became more acute with a longer exposure time. There was a linear dose-response relationship after 14 d exposure. Using predicted environmental concentrations for wastewaters it was found that AgNPs may pose a significant potential risk to the environment.

The NanoSustain and NanoValid project--two new EU FP7 research initiatives to assess the unique physical-chemical and toxicological properties of engineered nanomaterials.

In 2010, the EU FP NanoSustain project (247989) has been successfully launched with the objective to develop innovative solutions for the sustainable use, recycling and final treatment of engineered nanomaterials (ENMs). The same year, NanoValid (263147), a large-scale integrating EU FP7 project has been initiated and contract negotiations with the European Commission commenced, to develop new reference methods and materials applicable to the unique properties of ENMs. The paper presented will give an overview on the main objectives of these 2 new European research initiatives, on main tasks to achieve objectives, and on the impact on current standardization efforts and technical innovations.