Critical gaps in nanoplastics research and their connection to risk assessment

Reports of plastics, at higher levels than previously thought, in the water that we drink and the air that we breathe, are generating considerable interest and concern. Plastics have been recorded in almost every environment in the world with estimates on the order of trillions of microplastic pieces. Yet, this may very well be an underestimate of plastic pollution as a whole. Once microplastics (<5 mm) break down in the environment, they nominally enter the nanoscale (<1,000 nm), where they cannot be seen by the naked eye or even with the use of a typical laboratory microscope. Thus far, research has focused on plastics in the macro- (>25 mm) and micro-size ranges, which are easier to detect and identify, leaving large knowledge gaps in our understanding of nanoplastic debris. Our ability to ask and answer questions relating to the transport, fate, and potential toxicity of these particles is disadvantaged by the detection and identification limits of current technology. Furthermore, laboratory exposures have been substantially constrained to the study of commercially available nanoplastics; i.e., polystyrene spheres, which do not adequately reflect the composition of environmental plastic debris. While a great deal of plastic-focused research has been published in recent years, the pattern of the work does not answer a number of key factors vital to calculating risk that takes into account the smallest plastic particles; namely, sources, fate and transport, exposure measures, toxicity and effects. These data are critical to inform regulatory decision making and to implement adaptive management strategies that mitigate risk to human health and the environment. This paper reviews the current state-of-the-science on nanoplastic research, highlighting areas where data are needed to establish robust risk assessments that take into account plastics pollution. Where nanoplastic-specific data are not available, suggested substitutions are indicated

The impact of aminated surface ligands and silica shells on the stability, uptake, and toxicity of engineered silver nanoparticles

Inherent nanomaterial characteristics, composition, surface chemistry, and primary particle size, are known to impact particle stability, uptake, and toxicity. Nanocomposites challenge our ability to predict nanoparticle reactivity in biological systems if they are composed of materials with contrasting relative toxicities. We hypothesized that toxicity would be dominated by the nanoparticle surface (shell vs core), and that modulating the surface ligands would have a direct impact on uptake. We exposed developing zebrafish (Danio rerio) to a series of ~70 nm amine-terminated silver nanoparticles with silica shells (AgSi NPs) to investigate the relative influence of surface amination, composition, and size on toxicity. Like-sized aminated AgSi and Si NPs were more toxic than paired hydroxyl-terminated nanoparticles; however, both AgSi NPs were more toxic than the Si NPs, indicating a significant contribution of the silver core to the toxicity. Incremental increases in surface amination did not linearly increase uptake and toxicity, but did have a marked impact on dispersion stability. Mass-based exposure metrics initially supported the hypothesis that smaller nanoparticles (20 nm) would be more toxic than larger particles (70 nm). However, surface area-based metrics revealed that toxicity was independent of size. Our studies suggest that nanoparticle surfaces play a critical role in the uptake and toxicity of AgSi NPs, while the impact of size may be a function of the exposure metric used. Overall, uptake and toxicity can be dramatically altered by small changes in surface functionalization or exposure media. Only after understanding the magnitude of these changes, can we begin to understand the biologically available dose following nanoparticle exposure.This is the publisher’s final pdf. The published article is copyrighted by the author(s) and published by Springer. The published article can be found at: http://link.springer.com/journal/11051.Keywords: Dispersion, Zebrafish, Nanomaterials, Environmental and health effects, Surface chemistry, Silica shel

Nitric Oxide-Releasing Nanoparticles Prevent Propionibacterium acnes-Induced Inflammation by Both Clearing the Organism and Inhibiting Microbial Stimulation of the Innate Immune Response.

Propionibacterium acnes induction of IL-1 cytokines through the NLRP3 (NLR, nucleotide oligomerization domain-like receptor) inflammasome was recently highlighted as a dominant etiological factor for acne vulgaris. Therefore, therapeutics targeting both the stimulus and the cascade would be ideal. Nitric oxide (NO), a potent biological messenger, has documented broad-spectrum antimicrobial and immunomodulatory properties. To harness these characteristics to target acne, we used an established nanotechnology capable of generating/releasing NO over time (NO-np). P. acnes was found to be highly sensitive to all concentrations of NO-np tested, although human keratinocyte, monocyte, and embryonic zebra fish assays revealed no cytotoxicity. NO-np significantly suppressed IL-1β, tumor necrosis factor-α (TNF-α), IL-8, and IL-6 from human monocytes, and IL-8 and IL-6 from human keratinocytes, respectively. Importantly, silencing of NLRP3 expression by small interfering RNA did not limit NO-np inhibition of IL-1 β secretion from monocytes, and neither TNF-α nor IL-6 secretion, nor inhibition by NO-np was found to be dependent on this pathway. The observed mechanism by which NO-np impacts IL-1β secretion was through inhibition of caspase-1 and IL-1β gene expression. Together, these data suggest that NO-np can effectively prevent P. acnes-induced inflammation by both clearing the organism and inhibiting microbial stimulation of the innate immune response

Evaluating the use of zinc oxide and titanium dioxide nanoparticles in a metalworking fluid from a toxicological perspective

Adding nanoparticles (NPs) to metalworking fluids (MWFs) has been shown to improve performance in metal cutting. Zinc oxide nanoparticles (ZnO NPs) and titanium dioxide nanoparticles (TiO₂ NPs), for example, have exhibited the ability to improve lubricant performance, decrease the heat created by machining operations, reduce friction and wear, and enhance thermal conductivity. ZnO and TiO₂ NPs are also relatively inexpensive compared to many other NPs. Precautionary concerns of human health risks and environmental impacts, however, are especially important when adding NPs to MWFs. The goal of this research is to investigate the potential environmental and human health effects of these nanoenabled products during early design and development. This research builds on a prior investigation of the stability and toxicity characteristics of NPs used in metalworking nanofluids (MWnF™). The previous study only investigated one type of NP at one level of concentration. This research expands on the previous investigations through the valuation of three different types of NPs that vary in morphology (size and shape) and was conducted over a wide range of concentrations in the base fluid. In the presented work, mixtures of a microemulsion (TRIM® MicroSol® 585XT), two different types of TiO₂ NPs (referred to as TiO₂A and TiO₂B) and one type of ZnO NP were used to evaluate MWnF™ stability and toxicity. Dynamic light scattering (DLS) was used to assess stability over time and an embryonic zebrafish assay was used to assess toxicological impacts. The results reveal that, in general, the addition of these NPs increased toxicity relative to the NPfree formulation. The lowest rate of zebrafish malformations occurred at 5 g/L TiO₂A NP, which was even lower than for the base fluid. This result is particularly promising for future MWnF™ development, given that the mortality rate for 5 g/L TiO₂A was not significantly different than for the base fluid.Keywords: Environmental and health effects, Titanium Dioxide Nanoparticles, Zinc Oxide Nanoparticles, Nanotoxicology, Nanofluid Stabilit

ISA-TAB-Nano: A Specification for Sharing Nanomaterial Research Data in Spreadsheet-based Format

BACKGROUND AND MOTIVATION: The high-throughput genomics communities have been successfully using standardized spreadsheet-based formats to capture and share data within labs and among public repositories. The nanomedicine community has yet to adopt similar standards to share the diverse and multi-dimensional types of data (including metadata) pertaining to the description and characterization of nanomaterials. Owing to the lack of standardization in representing and sharing nanomaterial data, most of the data currently shared via publications and data resources are incomplete, poorly-integrated, and not suitable for meaningful interpretation and re-use of the data. Specifically, in its current state, data cannot be effectively utilized for the development of predictive models that will inform the rational design of nanomaterials. RESULTS: We have developed a specification called ISA-TAB-Nano, which comprises four spreadsheet-based file formats for representing and integrating various types of nanomaterial data. Three file formats (Investigation, Study, and Assay files) have been adapted from the established ISA-TAB specification; while the Material file format was developed de novo to more readily describe the complexity of nanomaterials and associated small molecules. In this paper, we have discussed the main features of each file format and how to use them for sharing nanomaterial descriptions and assay metadata. CONCLUSION: The ISA-TAB-Nano file formats provide a general and flexible framework to record and integrate nanomaterial descriptions, assay data (metadata and endpoint measurements) and protocol information. Like ISA-TAB, ISA-TAB-Nano supports the use of ontology terms to promote standardized descriptions and to facilitate search and integration of the data. The ISA-TAB-Nano specification has been submitted as an ASTM work item to obtain community feedback and to provide a nanotechnology data-sharing standard for public development and adoption

How should the completeness and quality of curated nanomaterial data be evaluated

Nanotechnology is of increasing significance. Curation of nanomaterial data into electronic databases offers opportunities to better understand and predict nanomaterials’ behaviour. This supports innovation in, and regulation of, nanotechnology. It is commonly understood that curated data need to be sufficiently complete and of sufficient quality to serve their intended purpose. However, assessing data completeness and quality is non-trivial in general and is arguably especially difficult in the nanoscience area, given its highly multidisciplinary nature. The current article, part of the Nanomaterial Data Curation Initiative series, addresses how to assess the completeness and quality of (curated) nanomaterial data. In order to address this key challenge, a variety of related issues are discussed: the meaning and importance of data completeness and quality, existing approaches to their assessment and the key challenges associated with evaluating the completeness and quality of curated nanomaterial data. Considerations which are specific to the nanoscience area and lessons which can be learned from other relevant scientific disciplines are considered. Hence, the scope of this discussion ranges from physicochemical characterisation requirements for nanomaterials and interference of nanomaterials with nanotoxicology assays to broader issues such as minimum information checklists, toxicology data quality schemes and computational approaches that facilitate evaluation of the completeness and quality of (curated) data. This discussion is informed by a literature review and a survey of key nanomaterial data curation stakeholders. Finally, drawing upon this discussion, recommendations are presented concerning the central question: how should the completeness and quality of curated nanomaterial data be evaluated

ISA-TAB-Nano: A Specification for Sharing Nanomaterial Research Data in Spreadsheet-based Format

Background and motivation: The high-throughput genomics communities have been successfully using standardized spreadsheet-based formats to capture and share data within labs and among public repositories. The nanomedicine community has yet to adopt similar standards to share the diverse and multi-dimensional types of data (including metadata) pertaining to the description and characterization of nanomaterials. Owing to the lack of standardization in representing and sharing nanomaterial data, most of the data currently shared via publications and data resources are incomplete, poorly-integrated, and not suitable for meaningful interpretation and re-use of the data. Specifically, in its current state, data cannot be effectively utilized for the development of predictive models that will inform the rational design of nanomaterials. Results: We have developed a specification called ISA-TAB-Nano, which comprises four spreadsheet-based file formats for representing and integrating various types of nanomaterial data. Three file formats (Investigation, Study, and Assay files) have been adapted from the established ISA-TAB specification; while the Material file format was developed de novo to more readily describe the complexity of nanomaterials and associated small molecules. In this paper, we have discussed the main features of each file format and how to use them for sharing nanomaterial descriptions and assay metadata. Conclusion: The ISA-TAB-Nano file formats provide a general and flexible framework to record and integrate nanomaterial descriptions, assay data (metadata and endpoint measurements) and protocol information. Like ISA-TAB, ISA-TAB-Nano supports the use of ontology terms to promote standardized descriptions and to facilitate search and integration of the data. The ISA-TAB-Nano specification has been submitted as an ASTM work item to obtain community feedback and to provide a nanotechnology data-sharing standard for public development and adoption

Completing the Link between Exposure Science and Toxicology for Improved Environmental Health Decision Making: The Aggregate Exposure Pathway Framework

Driven by major scientific advances in analytical methods, biomonitoring, computation, and a newly articulated vision for a greater impact in public health, the field of exposure science is undergoing a rapid transition from a field of observation to a field of prediction. Deployment of an organizational and predictive framework for exposure science analogous to the “systems approaches” used in the biological sciences is a necessary step in this evolution. Here we propose the aggregate exposure pathway (AEP) concept as the natural and complementary companion in the exposure sciences to the adverse outcome pathway (AOP) concept in the toxicological sciences. Aggregate exposure pathways offer an intuitive framework to organize exposure data within individual units of prediction common to the field, setting the stage for exposure forecasting. Looking farther ahead, we envision direct linkages between aggregate exposure pathways and adverse outcome pathways, completing the source to outcome continuum for more meaningful integration of exposure assessment and hazard identification. Together, the two frameworks form and inform a decision-making framework with the flexibility for risk-based, hazard-based, or exposure-based decision making