Metadata Stewardship in Nanosafety Research: Community-Driven Organisation of Metadata Schemas to Support FAIR Nanoscience Data.

The emergence of nanoinformatics as a key component of nanotechnology and nanosafety assessment for the prediction of engineered nanomaterials (NMs) properties, interactions, and hazards, and for grouping and read-across to reduce reliance on animal testing, has put the spotlight firmly on the need for access to high-quality, curated datasets. To date, the focus has been around what constitutes data quality and completeness, on the development of minimum reporting standards, and on the FAIR (findable, accessible, interoperable, and reusable) data principles. However, moving from the theoretical realm to practical implementation requires human intervention, which will be facilitated by the definition of clear roles and responsibilities across the complete data lifecycle and a deeper appreciation of what metadata is, and how to capture and index it. Here, we demonstrate, using specific worked case studies, how to organise the nano-community efforts to define metadata schemas, by organising the data management cycle as a joint effort of all players (data creators, analysts, curators, managers, and customers) supervised by the newly defined role of data shepherd. We propose that once researchers understand their tasks and responsibilities, they will naturally apply the available tools. Two case studies are presented (modelling of particle agglomeration for dose metrics, and consensus for NM dissolution), along with a survey of the currently implemented metadata schema in existing nanosafety databases. We conclude by offering recommendations on the steps forward and the needed workflows for metadata capture to ensure FAIR nanosafety data.

Integration among databases and data sets to support productive nanotechnology: Challenges and recommendations.

Many groups within the broad field of nanoinformatics are already developing data repositories and analytical tools driven by their individual organizational goals. Integrating these data resources across disciplines and with non-nanotechnology resources can support multiple objectives by enabling the reuse of the same information. Integration can also serve as the impetus for novel scientific discoveries by providing the framework to support deeper data analyses. This article discusses current data integration practices in nanoinformatics and in comparable mature fields, and nanotechnology-specific challenges impacting data integration. Based on results from a nanoinformatics-community-wide survey, recommendations for achieving integration of existing operational nanotechnology resources are presented. Nanotechnology-specific data integration challenges, if effectively resolved, can foster the application and validation of nanotechnology within and across disciplines. This paper is one of a series of articles by the Nanomaterial Data Curation Initiative that address data issues such as data curation workflows, data completeness and quality, curator responsibilities, and metadata.

Interpreting Mobile and Handheld Air Sensor Readings in Relation to Air Quality Standards and Health Effect Reference Values: Tackling the Challenges.

The US Environmental Protection Agency (EPA) and other federal agencies face a number of challenges in interpreting and reconciling short-duration (seconds to minutes) readings from mobile and handheld air sensors with the longer duration averages (hours to days) associated with the National Ambient Air Quality Standards (NAAQS) for the criteria pollutants-particulate matter (PM), ozone, carbon monoxide, lead, nitrogen oxides, and sulfur oxides. Similar issues are equally relevant to the hazardous air pollutants (HAPs) where chemical-specific health effect reference values are the best indicators of exposure limits; values which are often based on a lifetime of continuous exposure. A multi-agency, staff-level Air Sensors Health Group (ASHG) was convened in 2013. ASHG represents a multi-institutional collaboration of Federal agencies devoted to discovery and discussion of sensor technologies, interpretation of sensor data, defining the state of sensor-related science across each institution, and provides consultation on how sensors might effectively be used to meet a wide range of research and decision support needs. ASHG focuses on several fronts: improving the understanding of what hand-held sensor technologies may be able to deliver; communicating what hand-held sensor readings can provide to a number of audiences; the challenges of how to integrate data generated by multiple entities using new and unproven technologies; and defining best practices in communicating health-related messages to various audiences. This review summarizes the challenges, successes, and promising tools of those initial ASHG efforts and Federal agency progress on crafting similar products for use with other NAAQS pollutants and the HAPs. NOTE: The opinions expressed are those of the authors and do not necessary represent the opinions of their Federal Agencies or the US Government. Mention of product names does not constitute endorsement.

SPECIFIC BLOOD ABSORPTION PARAMETERS FOR 239PUO2 AND 238PUO2 NANOPARTICLES AND IMPACTS ON BIOASSAY INTERPRETATION.

Specific absorption parameters for 239PuO2 and 238PuO2 have been determined based on available biokinetic data from studies in rodents, and the impacts of these parameters on bioassay interpretation and dosimetry after inhalation of nanoPuO2 materials have been evaluated. Calculations of activities after an acute intake of nanoparticles of 239PuO2 and 238PuO2 are compared with the corresponding calculations using standard default absorption parameters using the International Commission on Radiological Protection (ICRP) 66 respiratory tract model. Committed effective doses are also evaluated and compared. In this case, it was found that interpretation of bioassay measurements with the assumption that the biokinetic behaviour of PuO2 nanoparticles is the same as that of micrometre-sized particles can result in an overprediction of the committed effective dose by two orders of magnitude. Although in this case the use of the default assumptions (5 µm AMAD, Type S) for assessing dose following inhalation exposure to airborne PuO2 nanoparticles appears to be conservative, the evaluation of situations involving PuO2 nanoparticles that may have different particle size and solubility properties should prudently follow the ICRP recommendation to obtain and use additional, material-specific information whenever possible.

Bridging the gap between exposure assessment and inhalation toxicology: Some insights from the carbon nanotube experience.

The early incorporation of exposure assessment can be invaluable to help design, prioritize, and interpret toxicological studies or outcomes. The sum total of the exposure assessment findings combined with preliminary toxicology results allows for exposure-informed toxicological study design and the findings can then be integrated, together with available epidemiologic data, to provide health effect relevance. With regard to engineered nanomaterial inhalation toxicology in particular, a single type of material (e.g. carbon nanotube, graphene) can have a vast array of physicochemical characteristics resulting in the potential for varying toxicities. To compound the matter, the methodologies necessary to establish a material adequate for in vivo exposure testing raises questions on the applicability of the outcomes. From insights gained from evaluating carbon nanotubes, we recommend the following integrated approach involving exposure-informed hazard assessment and hazard-informed exposure assessment especially for materials as diverse as engineered nanomaterials: 1) market-informed identification of potential hazards and potentially exposed populations, 2) initial toxicity screening to drive prioritized assessments of exposure, 3) development of exposure assessment-informed chronic and sub-chronic in vivo studies, and 4) conduct of exposure- and hazard-informed epidemiological studies.

INHALED AEROSOL DOSIMETRY: SOME CURRENT RESEARCH NEEDS.

After the presentation of 60 papers at the conference "Advancing Aerosol Dosimetry Research" (October 24-25, 2014 in Irvine, CA, USA), attendees submitted written descriptions of needed research. About 40 research needs were submitted. The suggestions fell into six broad categories: 1) Access to detailed anatomic data; 2) Access to subject-specific aerosol deposition datasets; 3) Improving current inhaled aerosol deposition models; 4) Some current experimental data needs and hot topics; 5) Linking exposure and deposition modeling to health endpoints; and 6) Developing guidelines for appropriate validation of dosimetry and risk assessment models. Summaries of suggestions are provided here as an update on research needs related to inhaled aerosol dosimetry modeling. Taken together, the recommendations support the overarching need for increased collaborations between dose modelers and those that use the models for risk assessments, aerosol medicine applications, design of toxicology experiments, and extrapolation across species. This paper is only a snapshot in time of perceived research needs from the conference attendees; it does not carry the approval of any agency or other group that plans research priorities or that funds research.

Use of the "Exposome" in the Practice of Epidemiology: A Primer on -Omic Technologies.

The exposome has been defined as the totality of exposures individuals experience over the course of their lives and how those exposures affect health. Three domains of the exposome have been identified: internal, specific external, and general external. Internal factors are those that are unique to the individual, and specific external factors include occupational exposures and lifestyle factors. The general external domain includes sociodemographic factors such as educational level and financial status. Eliciting information on the exposome is daunting and not feasible at present; the undertaking may never be fully realized. A variety of tools have been identified to measure the exposome. Biomarker measurements will be one of the major tools in exposomic studies. However, exposure data can also be obtained from other sources such as sensors, geographic information systems, and conventional tools such as survey instruments. Proof-of-concept studies are being conducted that show the promise of exposomic investigation and the integration of different kinds of data. The inherent value of exposomic data in epidemiologic studies is that they can provide greater understanding of the relationships among a broad range of chemical and other risk factors and health conditions and ultimately lead to more effective and efficient disease prevention and control.

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?

Toward the Responsible Development and Commercialization of Sensor Nanotechnologies.

Nanotechnology-enabled sensors (or nanosensors) will play an important role in enabling the progression toward ubiquitous information systems as the Internet of Things (IoT) emerges. Nanosensors offer new, miniaturized solutions in physiochemical and biological sensing that enable increased sensitivity, specificity, and multiplexing capability, all with the compelling economic drivers of low cost and high-energy efficiency. In the United States, Federal agencies participating in the National Nanotechnology Initiative (NNI) "Nanotechnology for Sensors and Sensors for Nanotechnology: Improving and Protecting Health, Safety, and the Environment" Nanotechnology Signature Initiative (the Sensors NSI), address both the opportunity of using nanotechnology to advance sensor development and the challenges of developing sensors to keep pace with the increasingly widespread use of engineered nanomaterials. This perspective article will introduce and provide background on the NNI signature initiative on sensors. Recent efforts by the Sensors NSI aimed at promoting the successful development and commercialization of nanosensors will be reviewed and examples of sensor nanotechnologies will be highlighted. Future directions and critical challenges for sensor development will also be discussed.

Adaptive Visual Sort and Summary of Micrographic Images of Nanoparticles for Forensic Analysis.

Image classification of nanoparticles from scanning electron microscopes for nuclear forensic analysis is a long, time consuming process. Months of analyst time may initially be required to sift through images in order to categorize morphological characteristics associated with nanoparticle identification. Subsequent assessment of newly acquired images against identified characteristics can be equally time consuming. We present INStINCt, our Intelligent Signature Canvas, as a framework for quickly organizing image data in a web-based canvas framework that partitions images based on features derived from convolutional neural networks. This work is demonstrated using particle images from an aerosol study conducted by Pacific Northwest National Laboratory under the auspices of the U.S. Army Public Health Command to determine depleted uranium aerosol doses and risks.

The Nanomaterial Data Curation Initiative: A collaborative approach to assessing, evaluating, and advancing the state of the field.

The Nanomaterial Data Curation Initiative (NDCI), a project of the National Cancer Informatics Program Nanotechnology Working Group (NCIP NanoWG), explores the critical aspect of data curation within the development of informatics approaches to understanding nanomaterial behavior. Data repositories and tools for integrating and interrogating complex nanomaterial datasets are gaining widespread interest, with multiple projects now appearing in the US and the EU. Even in these early stages of development, a single common aspect shared across all nanoinformatics resources is that data must be curated into them. Through exploration of sub-topics related to all activities necessary to enable, execute, and improve the curation process, the NDCI will provide a substantive analysis of nanomaterial data curation itself, as well as a platform for multiple other important discussions to advance the field of nanoinformatics. This article outlines the NDCI project and lays the foundation for a series of papers on nanomaterial data curation. The NDCI purpose is to: 1) present and evaluate the current state of nanomaterial data curation across the field on multiple specific data curation topics, 2) propose ways to leverage and advance progress for both individual efforts and the nanomaterial data community as a whole, and 3) provide opportunities for similar publication series on the details of the interactive needs and workflows of data customers, data creators, and data analysts. Initial responses from stakeholder liaisons throughout the nanoinformatics community reveal a shared view that it will be critical to focus on integration of datasets with specific orientation toward the purposes for which the individual resources were created, as well as the purpose for integrating multiple resources. Early acknowledgement and undertaking of complex topics such as uncertainty, reproducibility, and interoperability is proposed as an important path to addressing key challenges within the nanomaterial community, such as reducing collateral negative impacts and decreasing the time from development to market for this new class of technologies.

Commentary on the contributions and future role of occupational exposure science in a vision and strategy for the discipline of exposure science.

Exposure science is a holistic concept without prejudice to exposure source. Traditionally, measurements aimed at mitigating environmental exposures have not included exposures in the workplace, instead considering such exposures to be an internal affair between workers and their employers. Similarly, occupational (or industrial) hygiene has not typically accounted for environmental contributions to poor health at work. Many persons spend a significant amount of their lifetime in the workplace, where they maybe exposed to more numerous chemicals at higher levels than elsewhere in their environment. In addition, workplace chemical exposures and other exogenous stressors may increase epigenetic and germline modifications that are passed on to future generations. We provide a brief history of the development of exposure science from its roots in the assessment of workplace exposures, including an appendix where we detail current resources for education and training in exposure science offered through occupational hygiene organizations. We describe existing successful collaborations between occupational and environmental practitioners in the field of exposure science, which may serve as a model for future interactions. Finally, we provide an integrated vision for the field of exposure science, emphasizing interagency collaboration, the need for complete exposure information in epidemiological studies, and the importance of integrating occupational, environmental, and residential assessments. Our goal is to encourage communication and spur additional collaboration between the fields of occupational and environmental exposure assessment. Providing a more comprehensive approach to exposure science is critical to the study of the "exposome", which conceptualizes the totality of exposures throughout a person's life, not only chemical, but also from diet, stress, drugs, infection, and so on, and the individual response.

Application of an informatics-based decision-making framework and process to the assessment of radiation safety in nanotechnology.

The National Council on Radiation Protection and Measurements (NCRP) established NCRP Scientific Committee 2-6 to develop a report on the current state of knowledge and guidance for radiation safety programs involved with nanotechnology. Nanotechnology is the understanding and control of matter at the nanoscale, at dimensions between ∼1 and 100 nm, where unique phenomena enable novel applications. While the full report is in preparation, this paper presents and applies an informatics-based decision-making framework and process through which the radiation protection community can anticipate that nano-enabled applications, processes, nanomaterials, and nanoparticles are likely to become present or are already present in radiation-related activities; recognize specific situations where environmental and worker safety, health, well-being, and productivity may be affected by nano-related activities; evaluate how radiation protection practices may need to be altered to improve protection; control information, interpretations, assumptions, and conclusions to implement scientifically sound decisions and actions; and confirm that desired protection outcomes have been achieved. This generally applicable framework and supporting process can be continuously applied to achieve health and safety at the convergence of nanotechnology and radiation-related activities.

Turning Numbers into Knowledge: Sensors for Safety, Health, Well-being, and Productivity.

The industrial hygiene community has witnessed exponential growth in the use of sensors, especially by individuals. Remote wireless sensors are now monitoring worker health, the environment, agriculture, work sites, disaster relief, and "smart" buildings and facilities.

Opportunities and challenges of nanotechnology in the green economy.

In a world of finite resources and ecosystem capacity, the prevailing model of economic growth, founded on ever-increasing consumption of resources and emission pollutants, cannot be sustained any longer. In this context, the "green economy" concept has offered the opportunity to change the way that society manages the interaction of the environmental and economic domains. To enable society to build and sustain a green economy, the associated concept of "green nanotechnology" aims to exploit nano-innovations in materials science and engineering to generate products and processes that are energy efficient as well as economically and environmentally sustainable. These applications are expected to impact a large range of economic sectors, such as energy production and storage, clean up-technologies, as well as construction and related infrastructure industries. These solutions may offer the opportunities to reduce pressure on raw materials trading on renewable energy, to improve power delivery systems to be more reliable, efficient and safe as well as to use unconventional water sources or nano-enabled construction products therefore providing better ecosystem and livelihood conditions.However, the benefits of incorporating nanomaterials in green products and processes may bring challenges with them for environmental, health and safety risks, ethical and social issues, as well as uncertainty concerning market and consumer acceptance. Therefore, our aim is to examine the relationships among guiding principles for a green economy and opportunities for introducing nano-applications in this field as well as to critically analyze their practical challenges, especially related to the impact that they may have on the health and safety of workers involved in this innovative sector. These are principally due to the not fully known nanomaterial hazardous properties, as well as to the difficulties in characterizing exposure and defining emerging risks for the workforce. Interestingly, this review proposes action strategies for the assessment, management and communication of risks aimed to precautionary adopt preventive measures including formation and training of employees, collective and personal protective equipment, health surveillance programs to protect the health and safety of nano-workers. It finally underlines the importance that occupational health considerations will have on achieving an effectively sustainable development of nanotechnology.

Regulatory T cells modulate granulomatous inflammation in an HLA-DP2 transgenic murine model of beryllium-induced disease.

Susceptibility to chronic beryllium disease (CBD) is linked to certain HLA-DP molecules, including HLA-DP2. To elucidate the molecular basis of this association, we exposed mice transgenic (Tg) for HLA-DP2 to beryllium oxide (BeO) via oropharyngeal aspiration. As opposed to WT mice, BeO-exposed HLA-DP2 Tg mice developed mononuclear infiltrates in a peribronchovascular distribution that were composed of CD4(+) T cells and included regulatory T (Treg) cells. Beryllium-responsive, HLA-DP2-restricted CD4(+) T cells expressing IFN-γ and IL-2 were present in BeO-exposed HLA-DP2 Tg mice and not in WT mice. Using Be-loaded HLA-DP2-peptide tetramers, we identified Be-specific CD4(+) T cells in the mouse lung that recognize identical ligands as CD4(+) T cells derived from the human lung. Importantly, a subset of HLA-DP2 tetramer-binding CD4(+) T cells expressed forkhead box P3, consistent with the expansion of antigen-specific Treg cells. Depletion of Treg cells in BeO-exposed HLA-DP2 Tg mice exacerbated lung inflammation and enhanced granuloma formation. These findings document, for the first time to our knowledge, the development of a Be-specific adaptive immune response in mice expressing HLA-DP2 and the ability of Treg cells to modulate the beryllium-induced granulomatous immune response.

Exposures and cross-shift lung function declines in wildland firefighters.

Respiratory problems are common among wildland firefighters. However, there are few studies directly linking occupational exposures to respiratory effects in this population. Our objective was to characterize wildland fire fighting occupational exposures and assess their associations with cross-shift changes in lung function. We studied 17 members of the Alpine Interagency Hotshot Crew with environmental sampling and pulmonary function testing during a large wildfire. We characterized particles by examining size distribution and mass concentration, and conducting elemental and morphological analyses. We examined associations between cross-shift lung function change and various analytes, including levoglucosan, an indicator of wood smoke from burning biomass. The levoglucosan component of the wildfire aerosol showed a predominantly bimodal size distribution: a coarse particle mode with a mass median aerodynamic diameter about 12 µm and a fine particle mode with a mass median aerodynamic diameter < 0.5 µm. Levoglucosan was found mainly in the respirable fraction and its concentration was higher for fire line construction operations than for mop-up operations. Larger cross-shift declines in forced expiratory volume in one second were associated with exposure to higher concentrations of respirable levoglucosan (p < 0.05). Paired analyses of real-time personal air sampling measurements indicated that higher carbon monoxide (CO) concentrations were correlated with higher particulate concentrations when examined by mean values, but not by individual data points. However, low CO concentrations did not provide reliable assurance of concomitantly low particulate concentrations. We conclude that inhalation of fine smoke particles is associated with acute lung function decline in some wildland firefighters. Based on short-term findings, it appears important to address possible long-term respiratory health issues for wildland firefighters. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Occupational and Environmental Hygiene for the following free supplemental resources: a file containing additional information on historical studies of wildland fire exposures, a file containing the daily-exposure-severity questionnaire completed by wildland firefighter participants at the end of each day, and a file containing additional details of the investigation of correlations between carbon monoxide concentrations and other measured exposure factors in the current study.].

Nanoinformatics workshop report: Current resources, community needs, and the proposal of a collaborative framework for data sharing and information integration.

The quantity of information on nanomaterial properties and behavior continues to grow rapidly. Without a concerted effort to collect, organize and mine disparate information coming out of current research efforts, the value and effective use of this information will be limited at best. Data will not be translated to knowledge. At worst, erroneous conclusions will be drawn and future research may be misdirected. Nanoinformatics can be a powerful approach to enhance the value of global information in nanoscience and nanotechnology. Much progress has been made through grassroots efforts in nanoinformatics resulting in a multitude of resources and tools for nanoscience researchers. In 2012, the nanoinformatics community believed it was important to critically evaluate and refine currently available nanoinformatics approaches in order to best inform the science and support the future of predictive nanotechnology. The Greener Nano 2012: Nanoinformatics Tools and Resources Workshop brought together informatics groups with materials scientists active in nanoscience research to evaluate and reflect on the tools and resources that have recently emerged in support of predictive nanotechnology. The workshop goals were to establish a better understanding of current nanoinformatics approaches and to clearly define immediate and projected informatics infrastructure needs of the nanotechnology community. The theme of nanotechnology environmental health and safety (nanoEHS) was used to provide real-world, concrete examples on how informatics can be utilized to advance our knowledge and guide nanoscience. The benefit here is that the same properties that impact the performance of products could also be the properties that inform EHS. From a decision management standpoint, the dual use of such data should be considered a priority. Key outcomes include a proposed collaborative framework for data collection, data sharing and information integration.