Risk Governance of Nanomaterials: Review of Criteria and Tools for Risk Communication, Evaluation, and Mitigation

Nanotechnologies have been increasingly used in industrial applications and consumer products across several sectors, including construction, transportation, energy, and healthcare. The widespread application of these technologies has raised concerns regarding their environmental, health, societal, and economic impacts. This has led to the investment of enormous resources in Europe and beyond into the development of tools to facilitate the risk assessment and management of nanomaterials, and to inform more robust risk governance process. In this context, several risk governance frameworks have been developed. In our study, we present and review those, and identify a set of criteria and tools for risk evaluation, mitigation, and communication, the implementation of which can inform better risk management decision-making by various stakeholders from e.g., industry, regulators, and the civil society. Based on our analysis, we recommend specific methods from decision science and information technologies that can improve the existing risk governance tools so that they can communicate, evaluate, and mitigate risks more transparently, taking stakeholder perspectives and expert opinion into account, and considering all relevant criteria in establishing the risk-benefit balance of these emerging technologies to enable more robust decisions about the governance of their risks.

Tools that are easy to use and provide outputs that are easy to analyze, do not require specific expertise for their application. Information should be provided clearly to avoid arising misinterpretation. User-friendly tools are particularly relevant for Small and Medium Enterprises (SME) as those companies often do not have staff with experience or specific training suited to apply sophisticated protocols or models and understand the outcome. [1,2,7] C5: Quantitative information Quantitative tools estimate numerical values for consequences and their probabilities, in specific units defined when developing the context. However, this requires quantitative input information to function and they cannot be easily applied in data-poor situations, which reduces their overall applicability and thus the available risk information that could be communicated to stakeholders. [1,2,[7][8][9] C6: Documented applications -Trustworthiness Documented applications are the best way to test a tool, confirm its functionality and understand its strengths and limitations. Trustworthiness of input or output sources is important. [1,2,8,9] C7: Transparency of application/process To make it easy it is for stakeholders to quickly comprehend how specific data points and decision criteria influence decision-making. The process should be transparent so that the stakeholders can see what is going on and how decisions are being made. [1,6,7,10] C8: Comprehension Does the audience understand the content of the communication? [11] C9: Influence on final policy The output of the procedure should have a genuine impact on policy. [6] Effectiveness and efficiency Effectiveness and efficiency of risk governance processes is desired, especially for a better coordination of dialogues. The information exchange is typical for advanced phases of an inclusive risk debate where in the first phase of risk governance the focus lies on the establishment of a working dialogue and on the recruitment of relevant stakeholders. On the second phase, the call for more effectiveness and efficiency arises due to the different levels of knowledge and expertise of different stakeholders. [12][13][14] Flexible for variety of nanomaterials Framework or tools should be appropriate for various MNs and variations, to be as comprehensive, robust, and practical as possible. [8,[15][16][17]

Assessment tier
The assessment tier criterion distinguishes the "screening-level" from the "high-tiers" tools. [1,4,9] Lifecycle thinking It is important to assess the risks of MNs from a lifecycle perspective since the characteristics of some MNs are likely to change significantly during their lifetime, which would affect their hazard, exposure, and risk. [1,4,9] Agreement Does the audience agree with the recommendation or interpretation contained in the message? [11] Dose-response consistency Do people facing a higher dose of a hazard perceive the risk as greater and/or show a greater readiness to act than people exposed to a lower dose of this hazard? [11] Hazard-response consistency Do people facing a hazard that is higher in risk perceive the risk as greater and/or show a greater readiness to act than people exposed to a hazard that is lower in risk? [11] Uniformity Do audience members exposed to the same level of risk tend to have the same responses to this risk? [11] Audience evaluation Does the audience judge the message to have been helpful, accurate, clear, etc.? [11]

Types of communication failures
When different types of failures are possible, are the failures that occur generally of the more acceptable variety? [11]

Representativeness of participants
The public participants should comprise a broadly representative sample of the population of the affected public.
[6] Independence of true participants The participation process should be conducted in an independent, unbiased way. [6] Early involvement The public should be involved as early as possible in the process as soon as value judgments become salient. [6] Resource accessibility Public participants should have access to the appropriate resources to enable them to successfully fulfil their brief.
[6] Task definition The nature and scope of the participation task should be clearly defined [6] Cost-effectiveness The procedure should in some sense be cost-effective. [6] Persistence for being effective Risk communication activities need to be more sustained over time, better funded, and more ambitious in the goals adopted and the outcomes sought. [3] Enhancing trust and creating new principles for a democratic outcome In situations where high social distrust prevails, and this is increasingly common, a thorough revamping of the goals, structure, and conduct of risk communication will be needed. [3] Extent of damage Tools include adverse effects in natural units, such as fatalities, injuries, production losses, etc. [18] Probability of occurrence Estimate/assignment of the relative frequency of an event [18] Incertitude Overall indicator for different uncertainty components [18] Ubiquity Defines the geographic dispersion of potential damages (intra-generational justice) [18] Persistency Tools define the temporal extension of potential damage (intergenerational justice) [18] Accountability Tools enabling trustful relations between the actors and providing the foundation for monitoring and controlling the impacts of risk management outcomes. Accountability implies that claims posed by stakeholders can be substantiated and that scientific results that are brought into the discourse can be validated. [19][20][21] Shared strategic focus A shared strategic focus is one of the possible structuring and simplifying elements, which are essential for handling complexity, uncertainty, and ambiguity. The term "shared" point to the difference between a societal, dialogue-driven communication approach and a conventional public relations or information strategy. A "shared strategic focus" reflects the experience that stakeholders pursue their own strategies for reaching the required goals. Being strategic is not per se a problem for dialogue. [19] Sustainability General the responsible use of nanotechnologies and nanomaterials, one could claim that this could serve as the lead criterion for a shared strategic focus. The overall aim is to promote innovation in a societal acceptable and legitimate manner so that technological progress is served, and public acceptance and ethical acceptability is enhanced. [12,[19][20][21] Politically and legally realizable The need for the chosen solution to be politically and legally realizable [12,22] Ethically and publicly acceptable The need for chosen solution to be ethically and publicly acceptable [12,22]  Quantitative information x x x 3 Uncertainty analysis Documented applications / Trustworthiness Transparency of application / process Influence on final policy Fair and knowledgeable communication process x  x  x  x  x  10  Effectiveness and efficiency  x  x  x  x  x  11  Flexible for variety of nanomaterials  x  x  x  x  x  12  Assessment tier  x  x  x  x  x  13  Lifecycle thinking  x  x  x  x  x  14  Agreement  x  15  Dose-response consistency  x  x  x  16  Hazard-response consistency  x  x  x  17  Uniformity  x  18  Audience evaluation  x  x  x  x  x  19  Types of communication failures  x  20  Representativeness of participants  x  x  x  x  x  21  Independence of true participants  x  x  x  x  x  22 Early involvement Resource accessibility Task definition Persistence for being effective x 27 Enhancing trust and creating new principles for a democratic outcome x  28  Extent of damage  x  29  Probability of occurrence  x  30  Incertitude  x  31  Ubiquity  x  32  Persistency  x  33  Accountability  x  34  Shared strategic focus  x  x  x  x  x  35  Sustainability  x  x  x  x  x  36  Politically and legally realizable  x  x  37 Ethically and publicly acceptable x x Link-integration of models: Link or integration of various types of models (e.g., ERA-HH-exposure read-across grouping) in a decision-support tool The use of high-quality, peer-reviewed, and well-structured models fulfils the criteria quantitative information, Fair and knowledgeable communication process, effectiveness, and efficiency, Flexible for variety of nanomaterials during the complete RG cycle. Evidently the complexity of the RG paradigm during the life cycle of a nanomaterial from the innovation stage to the end of life can be supported by the use of tailored trustworthy models that can be integrated in the HUB and provide multiple sources of assessment to the users Data extraction/migration/interoperability features: Various import, migration, and export features increase user-friendliness of the systems and interoperability Effective data handling within a decision-support tool is essential for all the RG stages. A system should allow the user to import-migrate-export data in the easiest and fastest way possible, to improve not only risk assessment and management results but to allow efficient risk communication. Both solutions present peculiar advantages, a HUB-based decision-support tool linking all the important information sources and models within a single location makes the acquisition of knowledge faster while the application of models needs more resources. On the opposite side an integrated solution within a single web application requires more initial efforts to grasp the logic in the tool but speeds up models' application by supplying a homogeneous integrated user interface. Logistic regression: A predictive regression analysis that can be used to describe data and to explain the relationship between one dependent variable and one or more independent variables Logistic regression is a tool for binomial classification based on learning sets. It is useful in uncertainty analysis, grouping, and the increase of effectiveness and efficiency of decision-support tools 43 Statistical methods / Methodology C1, C5 Neural networks: An alternative to regression models and other related statistical techniques in the areas of statistical prediction and classification Neural networks can be used to predict outcomes of complex nonlinear processes and is therefore useful in decision analysis for grouping or examination of possible alternatives outcomes 44 Statistical methods / Methodology C1, C5 Stable results: Calibration of models to be used in decision-support activities (sensitivity analysis and performance testing) The analysis of models through sensitivity analysis and performance testing supports the fulfilment of criteria uncertainty analysis and quantitative information -III -Description of Identified Tools Table S5. Risk pre-assessment tools descriptions and references.

Tool Name Description References Sector
NanoRiskRadar Automatic identification of new risks previously developed for the insurance sector to assess internet-based sources measuring singularity and ubiquity of new information. The tool will also include NM-specific methods to consider cognitive factors (interdependencies between context, objectives and biases) for risk perception.

Under development/caLIBRAte Scanning
Causal diagram assessment The causal diagram has been developed as a method to handle the complexity of issues on NP safety, from their exposure to the effects on the environment and health. It gives an overview of available scientific information starting with common sources of NPs and their interactions with various environmental processes that may pose threats to both human health and the environment.
[23] Scanning This paper proposes such a quantitative risk prioritization tool, based on a multicriteria decision analysis algorithm, which combines advanced exposure and dose-response modeling to calculate margins of exposure (MoE) for several MN in order to rank their occupational risks. [4] Ranking / priorization MCDA procedure for hazard screening of ENMs A quantitative weight of evidence (WOE) framework that uses multicriteria decision analysis methodology for integrating individual studies on nanomaterial hazard resulting from physicochemical and toxicological properties of nanomaterials. The WOE approach explicitly integrates expert evaluation of data quality of available information. Application of the framework is illustrated for titanium dioxide nanoparticles (nano-TiO2), but the approach is designed to compare the relative hazard of several nanomaterials as well as emerging stressors in general.
[32] Ranking / priorization MCDA procedure for prioritization of Occupational exposure scenarios of NMs An approach for relative exposure screening of ENMs. An exposure model explicitly implementing quantitative WOE methods and uses expert judgment for filling data gaps in the available evidence-base. Application of the framework is illustrated for screening of exposure scenarios for nano-scale titanium dioxide, carbon nanotubes, and fullerenes, but it is applicable to other nanomaterials as well. [33] Ranking / priorization Tool for ENM-Application Pair Risk Ranking (TEARR) This study examines the use of one risk ranking tool that incorporates both quantitative and qualitative information regarding the potential human health risks of ENMs, focused primarily on worker and soldier health. Using a case study involving Army materiel (i.e., equipment), a relative risk ranking algorithm is proposed that accounts for not only the physicochemical characteristics of the ENMs, but also the characteristics of the Army materiel. In this way, the resulting risk potential for soldiers and workers is not solely based on the inherent characteristics of the ENMs but is also influenced within the context of the technology being developed.
[34] Ranking / priorization Stochastic multicriteria acceptability analysis (SMAA-TRI) A decision-support system for classifying nanomaterials into different risk categories. The classification system is based on a set of performance metrics that measure both the toxicity and physicochemical characteristics of the original materials, as well as the expected environmental impacts through the product life cycle. Stochastic multicriteria acceptability analysis (SMAA-TRI), a formal decision analysis method, was used as the foundation for this task. This method allowed us to cluster various nanomaterials in different ecological risk categories based on our current knowledge of nanomaterial physicochemical characteristics, variation in produced material, and best professional judgments. SMAA-TRI uses Monte Carlo simulations to explore all feasible values for weights, criteria measurements, and other model parameters to assess the robustness of nanomaterial grouping for risk management purposes. [35] Classification

NRST (Nanomaterial Risk-Screening Tool)
A decision-support framework relating key nanomaterial physicochemical and product characteristics to important hazard and exposure indicators. This framework for aiding risk managers' decisions under uncertainty provides the foundation for the development of a transparent and adaptable screening tool that can inform the management of potential risks. [36] Screening NanoRiskCat A screening tool that can identify, categorize and rank exposures and effects of nanomaterials used in consumer products based on data available in the peer-reviewed scientific literature and other regulatory relevant sources of information and data. The primary focus was on nanomaterials relevant for professional end users and consumers as, as well as nanomaterials released into the environment. The wider goal of NanoRiskCat is to help manufacturers, downstream end users, regulators, and other stakeholders to evaluate, rank and communicate the potential for exposure and effects through a tiered approach in which the specific applications of a given nanomaterial are evaluated.

CB NanoTool
The tool estimates an emission probability (without considering exposure controls) and severity band and provides advice on what engineering controls to use. It includes nine domains covering handling of liquids, powders, and abrasion of solids. Combines hazard "severity" and exposure "probability" scores in a matrix to obtain a level of risk and associated controls out of 4 possible levels of increasing risk and associated controls.
[ [39][40][41] Control-banding Precautionary Matrix for Synthetic Nanomaterials (Swiss Precautionary Matrix) This tool helps to determine if exposure needs to be controlled, providing advice on whether a precautionary approach is required under normal working conditions, in the worst-case scenario and for the environment.

Screening Tree Tool
A screening tool to combine the LCA approach with chemical hazard information (human health and environmental hazard) and exposure pathways. This enabled the product designers to efficiently identify which chemicals and raw materials pose significant hazards and the important exposure pathways. This tool can also be used as a screening tool for new designs/product formulations.

[43-45] Screening
NanoGRID Designed to guide users through a tiered testing framework to help characterize the durability, degradation, potential for nano-scale material release and environmental health and safety implications of nano-enabled products.

ANSES Nano
The ANSES CB nanotool was developed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) to be applied for conducting risk assessment and risk management of work with manufactured nanomaterials or nano-enabled products in industrial settings. [47,48] Control-banding Table S6. Risk concern-assessment tools descriptions and references.

SUNDS
The Sustainable Nanotechnology Decision-Support System (SUNDS) addresses current nanotechnology risk assessment and management needs. The SUNDS conceptual decision framework expands the focus from nanotechnology risk assessment and management to emerging risk governance needs. It has a two-tier structure comprising screening and advanced tools to address varying data availability and stakeholder needs. [49,50] Risk assessment Nanosafer NanoSafer is a combined control-banding and risk management tool that enables assessment of the risk level and recommended exposure control associated with production and use of manufactured nanomaterials (e.g., nanoparticles, nanoflakes, nanofibers, and nanotubes) in specific work scenarios. In addition to manufactured nanomaterials, the tool can also be used to assess and manage emissions from nanoparticle-forming processes. Uses data on material properties, processes, and production facilities to estimate occupational risk. The tool uses the Risk Quotient (i.e., the ratio of an exposure dose to a human effect threshold) to estimate risk deterministically. The upcoming new version, NanoSafer 2, will be capable of estimating exposure from spray processes. In addition, NanoSafer 2 can perform nano-specific hazard assessment based on read-across between MNs based on specific material properties and hazard indicators, tested for performance against in vivo experiments.
[51] Risk assessment GUIDEnano Assessment and mitigation of nano-enabled product risks on human and environmental health. To develop innovative methodologies to evaluate and manage human and environmental health risks of nano-enabled products, considering the whole product life cycle. Using this tool, industry will be able to evaluate and efficiently mitigate possible health risks for workers, consumers, and the environment associated with the use of nanotechnologies.
[52] -http://www.guidenano.eu/ Risk assessment ECETOC TRA v3.1 To assess risks associated with nanotechnology operations. Control-banding (CB) strategies (a qualitative risk characterization and management strategy) offer simplified solutions for controlling worker exposures to constituents that are found in the workplace in the absence of firm toxicological and exposure data. Combines hazard "severity" and exposure "probability" scores in a matrix to obtain a level of risk and associated controls out of 4 possible levels of increasing risk and associated controls.

LICARA nanoscan
The main goal of LICARA is to develop a structured lifecycle approach for nanomaterials that enables the balance of health/environmental risks of nanomaterials in view of paucity of data against their benefits, and that further allows a comparison with the risks and the benefits of the conventional (non-nano) products. It estimates economic, environmental, and social opportunities. This tool is specifically intended for use by SME to support them in communicating with regulators, and potential clients and investors.
[54] Risk assessment EGRET2 ESIG has developed a tool (termed the ESIG GES Risk and Exposure Tool or "EGRET") that enables users to construct their own consumer CSA/ES for a particular area of use within the ESIG/ESVOC library. This library was constructed based on the results of the various communication and use mapping activities that have been undertaken with major Downstream User (DU) groups (e.g., the consumer use of solvents in coatings, which is in turn described by a set of product categories and sub-categories).

BAUA Sprayexpo 2.3
SprayExpo is an Excel model for calculation the airborne concentration of the respirable, the thoracic and the inhalable fraction of aerosols containing biocidal substances in indoor environments originating from the release of liquid biocidal sprays.

Stoffenmanager Nano
Stoffenmanager Nano allows you to qualitatively assess occupational health risks from inhalation exposure to Manufactured Nano-Objects (MNO). Risk Management Measures may be selected or included in the Action Plan. Stoffenmanager Nano is a "work-in-process" online tool that reflects the current knowledge of risks related to working with nanomaterials.

ANSES Nano
The ANSES CB nanotool was developed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) to be applied for conducting risk assessment and risk management of work with manufactured nanomaterials or nano-enabled products in industrial settings. [47,48] Risk assessment

Control-banding nanotool
Control-banding (CB) strategies offer simplified solutions for controlling worker exposures to constituents that are found in the workplace in the absence of firm toxicological and exposure data. These strategies may be particularly useful in nanotechnology applications, considering the overwhelming level of uncertainty over what nanomaterials present as potential work-related health risks and how these risks can be assessed and managed appropriately. The CB nanotool is a novel CB approach being used at the Lawrence Livermore National Laboratory (LLNL), by both experts and non-experts, to assess risks associated with nanotechnology operations and prescribe appropriate engineering controls. CB nanotool creates a severity and probability risk matrix as an output, which contains four different risk levels.
[ [39][40][41] Risk assessment Precautionary Matrix for Synthetic Nanomaterials (Swiss Precautionary Matrix) This tool helps to determine if exposure needs to be controlled, providing advice on whether a precautionary approach is required under normal working conditions, in the worst-case scenario and for the environment. [42] Risk assessment Multimedia mass balance model, development of the SimpleBox model. Air, water, soil, sediment compartments. Computes steady state concentrations in all compartments at local, regional, or continental scale. Mechanistic representations of processes. Parameters may be estimated from theory or experiment. Could be applied to dynamic predictions.
[58] Risk assessment NanoDUFLOW Nano enable extension of the DUFLOW hydrological mode. NanoDUFLOW accounts for the ENP transformation processes homo-and hetero-aggregation, dissolution, and degradation, coupled with the transport processes sedimentation, resuspension, and burial to deeper sediment layers. Aggregation and sedimentation are based on Von Smoluchowski and Stokes theories. Aggregation is calculated from the collision frequency for peri-and ortho-kinetic aggregation as well as aggregation due to differential settling, and attachment efficiencies. Hetero-aggregation is modeled for five ENP size classes interacting with five SS size classes leading to 25 classes of hetero-aggregates, all modeled in place and time. [59,60] Risk assessment MendNano Multimedia mass balance model. Air, water, soil, sediment, biota compartments. Handles size distributions of ENM.
Computes concentrations in each compartment over time. Processes: dry and wet deposition to foliage and ground, foliage washoff, aerosolization, wind resuspension, soil-water runoff, hetero-aggregation, dissolution, sedimentation, sediment resuspension, and burial, biotic uptake, and elimination, plant root uptake.

RedNano
Integrated simulation tool for assessing the potential release and environmental distribution of nanomaterials based on lifecycle assessment approach and multimedia compartmental modeling coupled with mechanistic intermedia transport processes. The RedNano simulation tool and its web-based software implementation enables scenario analysis to assess the response of an environmental system to various release scenarios. RedNano incorporates the MendNano model. [62] Risk assessment GWAVA with water quality module Aquatic-only model predicts Predicted Environmental Concentrations (PECs) for river reaches across Europe. Hydrology includes STP discharges, runoff, and water abstraction. Emissions based on per capita NM loadings to sewage and sewage discharge per grid cell. NM transformations modeled via lumped 1st order kinetic loss. [63,64] Risk assessment

ConsExpo nano
Tool for the assessment of consumer exposure to nanomaterials via inhalation (spray scenario as well as custom scenarios). The outcome of the assessment is an alveolar load in the lungs as one of the most critical determinants of inflammation of the lungs is both the magnitude and duration of the alveolar load of a nanomaterial. To estimate the alveolar load arising from the use of nano-enabled spray products, ConsExpo nano combines models that estimate the external aerosol concentration in indoor air, with models that estimate the deposition in and clearance of inhaled aerosol from the alveolar region.

Stochastic Materials Flow Model
This model treats input parameters, such as nano-specific production and consumption volumes, fate pathways and transfer coefficients as probability distributions (Monte Carlo, Bayesian and Markov Chain) that are built based on empirical data and expert judgment. Therefore, the outputs of the model are distributions of possible PECs, and its application always includes analysis of variability and uncertainty. [70] Risk assessment Explorative particle flow analysis (PFA) Dynamic, quantitative environmental fate model based on colloidal chemistry. Estimates particle number concentrations in the aquatic environments resulting from processes such as materials inflow, homo-and hetero-agglomeration/aggregation and sedimentation, which are considered driving forces behind the transport of MN in waters and their potential elimination from them. [71,72] Risk assessment

REACHnano ToolKit
A web-based toolkit to support the risk assessment and promote the safe use of NMs along their life cycle. Contains an inventory with information about ca. 30 commonly used NMs. Environmental risk assessment is done through a model flow analysis probabilistic matter (PMFA). The occupational risk assessment tool is based on a combination of control-banding approach, exposure estimation tools, and new templates of exposure scenarios developed specifically for the case of NMs. Users may estimate the exposure depending on the operative conditions and applied risk management measures. Once all the necessary data is introduced, the model estimates if one (or more) scenarios can be dangerous for the worker.
http://tools.lifereachnano.eu/ Risk assessment NanoRiskCat A screening tool that can identify, categorize and rank exposures and effects of nanomaterials used in consumer products based on data available in the peer-reviewed scientific literature and other regulatory relevant sources of information and data. The primary focus was on nanomaterials relevant for professional end users and consumers as, as well as nanomaterials released into the environment. The wider goal of NanoRiskCat is to help manufacturers, downstream end users, regulators, and other stakeholders to evaluate, rank and communicate the potential for exposure and effects through a tiered approach in which the specific applications of a given nanomaterial are evaluated. [37,38] Risk assessment

PBPK model
A generic physiologically based pharmacokinetic (PBPK) model for nanomaterials, kinetic tool for estimating internal human exposure (post-exposure absorption, distribution and excretion (ADME) of MN). Can be used to characterize the ADME profiles of the MN for a diverse range of species based on particle type and physicochemical properties. Can also help to develop MN-specific uncertainty factors for interspecies differences in kinetics (e.g., between rodents and humans). PBPK modeling may facilitate extrapolation in exposure duration, e.g., tissue concentration levels for chronic exposure. An adaptation and extension of an earlier PBPK model for larger particles, calibrated using data from EU ENPRA, NANOMMUNE, and NANOTEST projects.
[73] Risk assessment NANEX Exposure Scenario Data Library Library of 9 occupational exposure scenarios for a variety of manufactured nanomaterials [9,29] Risk assessment Nano to go! Guidance document prepared within the EU FP7 NanoValid project for the safe handling of nanomaterials. Contents include a brochure on "Safe handling of nanomaterials and other advanced materials at workplaces" and reports on case studies.
[74] http://www.nanosafetycluster.eu/nanoToGo/ Risk assessment Particle dosimetry model for airborne particles. The MPPD model is a computational model that can be used for estimating human and rat airway particle dosimetry. The model is applicable to risk assessment, research, and education. The MPPD model calculates the deposition and clearance of monodisperse and polydisperse aerosols in the respiratory tracts of rats and human adults and children (deposition only) for particles ranging in size from ultrafine (0.01 µ m) to coarse (20 µ m). [75,76] Risk assessment SOP Tiered Approach for the assessment of exposure to airborne nano-objects in workplaces This SOP covers the overall strategy of assessing exposure to airborne nano-objects in workplaces, following a tiered approach, which contains 3 hierarchical tiers: tier 1: information gathering, tier 2: basic assessment and tier 3: expert assessment. This SOP describes the general procedure, whereas the measurements in tier 2 and tier 3 are described in three main SOPs: Screening, Sampling, and Expanded Measurement. Each of these main SOPs is accompanied by sub-SOPs describing the use of instruments, sample preparation, and data evaluation.

AMBIT2 tool
Software tool designed to support companies by facilitating high-quality chemical safety prediction. Based on a "predictive toxicity model", applies the principles of read-across and categorization. AMBIT supports nanomaterials storage (components, physicochemical and biological characterization) and query (connected with eNanoMapper). [78] Risk assessment NanoGRID Designed to guide users through a tiered testing framework to help characterize the durability, degradation, potential for nano-scale material release and environmental health and safety implications of nano-enabled products. [46] Risk assessment NanoNextNL DSS (under development) The NanoNextNL DSS aims at helping to identify ENPs and applications that should get priority in the risk assessment. [79] Risk assessment Table S7. Risk evaluation tools descriptions and references.

SUNDS
The Sustainable Nanotechnology Decision-Support System (SUNDS) addresses current nanotechnology risk assessment and management needs. The SUNDS conceptual decision framework expands the focus from nanotechnology risk assessment and management to emerging risk governance needs. It has a two-tier structure comprising screening and advanced tools to address varying data availability and stakeholder needs. [49,50] Risk characterization NanoSafer NanoSafer is a combined control-banding and risk management tool that enables assessment of the risk level and recommended exposure control associated with production and use of manufactured nanomaterials (e.g., nanoparticles, nanoflakes, nanofibers, and nanotubes) in specific work scenarios. In addition to manufactured nanomaterials, the tool can also be used to assess and manage emissions from nanoparticle-forming processes.
[51] Risk characterization NanoRiskCat A screening tool that can identify, categorize and rank exposures and effects of nanomaterials used in consumer products based on data available in the peer-reviewed scientific literature and other regulatory relevant sources of information and data. The primary focus was on nanomaterials relevant for professional end users and consumers as, as well as nanomaterials released into the environment. The wider goal of NanoRiskCat is to help manufacturers, downstream end users, regulators, and other stakeholders to evaluate, rank and communicate the potential for exposure and effects through a tiered approach in which the specific applications of a given nanomaterial are evaluated. A nano-risk assessment tool to assist regulators, research laboratories, and organizations in managing engineered nanomaterials. This tool consists of a questionnaire, which helps to register the chemical composition and the physical form of the nanomaterials manufactured or used, and the safety measures applied to nanoparticle exposure prevention at the workplace.

REACHnano ToolKit
A web-based toolkit to support the risk assessment and promote the safe use of NMs along their life cycle. Contains an inventory with information about ca. 30 commonly used NMs. Environmental risk assessment is done through a model flow analysis probabilistic matter (PMFA). The occupational risk assessment tool is based on a combination of control-banding approach, exposure estimation tools, and new templates of exposure scenarios developed specifically for the case of NMs. Users may estimate the exposure depending on the operative conditions and applied risk management measures. Once all the necessary data is introduced, the model estimates if one (or more) scenarios can be dangerous for the worker.
http://tools.lifereachnano.eu/ Risk characterization nanoinfo.org A web-platform built to support the nanoinformatics effort by developing and providing state-of-the-art resources and tools dedicated to environmental impact assessment of engineered nanomaterials (ENMs). Consists of: * LearNano: lifecycle assessment of the environmental release of ENMs * MendNano: multimedia compartmental simulation model of the environmental distribution of ENMs * ToxNano: toxicity data analysis of ENMs that supports high-throughput screening and high content studies * NanoEIA: in silico environmental impact analysis platform that enables evaluation of potential impacts and thus can assist in developing risk management options in support of safe-by-design of ENMs considering multicriteria analyses [62] Risk characterization FINE Baseline probabilistic model that incorporates nano-specific characteristics and environmental parameters, along with elements of exposure potential, hazards, and risks from MN. Bayesian networks in combination with expert elicitation as a tool for nanomaterial risk forecasting. [83,84] Risk characterization

LICARA nanoSCAN
Determines and weighs of the benefits and risks over the lifecycle of MN-based products. This tool is specifically intended for use by SME to support them in communicating with regulators, and potential clients and investors. It uses principles and assessment criteria from the Precautionary Matrix, NanoRiskCat and Stoffenmanager Nano, and integrates them with expert judgment through MCDA.
[54] Risk characterization NanoCommission assessment tool A downloadable questionnaire (available only in German). The set of assessment criteria applied to all lifecycle stages are probability of exposure, physicochemical properties, environmental fate and toxicology/ecotoxicology. A similar product not containing nanoparticles is used as a reference. Benefits and risks are considered for consumers, society, environment, and companies at different stages of the lifecycle of a nanomaterial. A classification into two groups is made depending on whether there is cause for concern or not.
[85] Risk characterization Table S8. Risk management decision-making support tools descriptions and references.

SUNDS
The Sustainable Nanotechnology Decision-Support System (SUNDS) addresses current nanotechnology risk assessment and management needs. The SUNDS conceptual decision framework expands the locus from nanotechnology risk assessment and management to emerging risk governance needs. It has a two-tier structure comprising screening and advanced tools to address varying data availability and stakeholder needs. [49,50] Risk management CB Nanotool The tool estimates an emission probability (without considering exposure controls) and severity band and provides advice on what engineering controls to use. It includes nine domains covering handling of liquids, powders, and abrasion of solids. Combines hazard "severity" and exposure "probability" scores in a matrix to obtain a level of risk and associated controls out of 4 possible levels of increasing risk and associated controls.

Stoffenmanager Nano
Ranks potential health risks from workplace inhalation exposure to MN and proposes effective RMM. It concerns single particles as well as agglomerates or aggregates and applies to MN that meet all of the following criteria: i) particles are not (water) soluble; ii) particles are synthetically produced and not released as unintentional by-product of e.g., incomplete combustion processes; iii) the size of the primary particles is smaller than 100 nm and/or the specific surface area of the nanopowder is larger than 60 m 2 /g [57] Risk management

ANSES Nano
The ANSES CB nanotool was developed by the French Agency for Food, Environmental and Occupational Health & Safety (ANSES) to be applied for conducting risk assessment and risk management of work with manufactured nanomaterials or nano-enabled products in industrial settings. [47,48] Risk management Precautionary Matrix for Synthetic Nanomaterials (Swiss Precautionary Matrix) This tool helps to determine if exposure needs to be controlled, providing advice on whether a precautionary approach is required under normal working conditions, in the worst-case scenario and for the environment. [42] Risk management NanoSafer NanoSafer is a combined control-banding and risk management tool that enables assessment of the risk level and recommended exposure control associated with production and use of manufactured nanomaterials (e.g., nanoparticles, nanoflakes, nanofibers, and nanotubes) in specific work scenarios. In addition to manufactured nanomaterials, the tool can also be used to assess and manage emissions from nanoparticle-forming processes.
[51] Risk management NanoRiskCat A screening tool that can identify, categorize and rank exposures and effects of nanomaterials used in consumer products based on data available in the peer-reviewed scientific literature and other regulatory relevant sources of information and data. The primary focus was on nanomaterials relevant for professional end users and consumers as, as well as nanomaterials released into the environment. The wider goal of NanoRiskCat is to help manufacturers, downstream end users, regulators, and other stakeholders to evaluate, rank and communicate the potential for exposure and effects through a tiered approach in which the specific applications of a given nanomaterial are evaluated. [37,38] Risk management A low-cost/evidence-based tool A low-cost/evidence-based for assessing and managing the risks associated with exposure to Carbon Nanofiber [86] Risk management

XL Insurance Database
An assessment strategy based on the protocol that XL Insurance uses for calculating insurance premiums for chemical industries. The protocol is mainly used to perform risk assessment for the manufacture of nanomaterials, by focusing on the characteristics of the materials and production processes. [87,88] Risk management / Insurance sector Nano-specific Risk Management Library The main purpose of the tool is to provide small and medium sized enterprises (SMEs), large companies, and other relevant stakeholders with an easy to use tool to select proper measures to achieve a high level of protection of the human health and the environment against ENMs, assisting them in the selection of adequate personal protective equipment (PPE) and engineering controls (EC) in order to prevent exposure to ENMs and release in the workplace.

RIVM
Risk management Table S9. Safety-by-design-monitoring tools descriptions and references.

Tool name Description References Sector
ProSafe SbD Implementation Concept SbD implementation concept based on the NANoREG SbD concept. The four main elements are: #1 The workflows in industrial innovation processes or actor-specific needs #2 The Safety Dossier #3 The Safety Profile #4 Harmonized inventory of SbD protocols, procedures, and data [89] SbD CENARIOS CENARIOS, the first certifiable nano-specific risk management and monitoring system. CENARIOS provides a "State-of-the Art" hazard and risk assessment, encompassing risk monitoring tools to minimize the potential risks. [90] Monitoring