Final Report Summary - GUIDENANO (Assessment and mitigation of nano-enabled product risks on human and environmental health: Development of new strategies and creation of a digital guidance tool for nanotech industries)
Executive Summary:
Current uncertainties on the safety of nano-enabled products need to be urgently and carefully addressed. Otherwise, public fears could end up blocking the benefits of nanotechnology. Sound scientific information must be generated to identify potential risks of nano-enabled products on human and ecosystems health, taking into consideration all stages of the life cycle of these products. Some web-based control banding tools are already available, but these mainly focus on the worksite and are mainly intended at the identification of hotspots rather than a complete risk assessment.
The recently finalized EU FP7 project GUIDEnano aimed to develop a methodology to address the human and environmental health risks of nano-enabled products, considering the whole product life cycle, i.e. synthesis of nanomaterials (NM), manufacturing of NM-enabled products, use, and end-of-life phase. The project consortium consisted of around 30 international partners, including universities, research institutes and industrial partners developing NM-enabled products.
The GUIDEnano consortium reviewed and structured the state of the art knowledge on the risk assessment of nanomaterials, and identified a series of gaps that were addressed by a series of experimental studies and comprehensive literature data analysis. The project incorporated as well 8 industrial case studies that were investigated in detail and were used to evaluate the performance of the Tool.
The main result of this 3.5-year effort is the GUIDEnano Tool, which incorporated in a structured-way all knowledge compiled/generated by the consortium in order to provide a quantitative human and environmental risk evaluation. Where needed, the Tool allows to assess how different risk management measures would modify the risk estimation, for example by providing the efficiency of methods for exposure reduction or by evaluating materials that are produced with the goal to be inherently safe(r) by design.
The correct implementation of this guidance ensures that the risks associated with a NM-enabled product, throughout its whole life cycle/ value chain, have been appropriately evaluated and mitigated to an acceptable level, according to the most recent knowledge at the time of implementation. The evaluation of a NM-enabled product using this Tool will also be useful for risk communication to regulators, insurance companies, and society.
Project Context and Objectives:
The main objective of GUIDEnano was to develop innovative methodologies to evaluate and manage human and environmental health risks of nano-enabled products, considering the whole product life cycle: synthesis of NM, manufacturing of NM-enabled products, use, and end-of-life phase (including recycling) (Figure 1). These developments were incorporated into an interactive web-based Guidance Tool, which guides the NM-enabled product developers (mainly industry) into the design and application of the most appropriate risk assessment & mitigation strategy for a specific product.
The specific goals of the project were the following:
1. To develop methodologies to evaluate the risks of a wide diversity of nano-enabled products on human and environmental health, throughout their life cycle.
2. To develop innovative solutions to reduce the identified risks. A wide range of risk mitigation strategies and guidance on the selection of the most appropriate measures for each scenario associated to an unacceptable risk will be provided.
3. To integrate the risk evaluation and mitigation strategies into the GUIDEnano Tool and to carry out an iterative process of performance testing, feedback and improvement steps to validate its suitability and applicability to real-case NM-enabled products, including a detailed plan for the hosting and maintenance of the GUIDEnano Tool after the life time of the project.
4. To efficiently communicate to consumers, regulators and insurance communities that, by following the GUIDEnano Tool, risks associated with an NM-enabled product have been adequately identified, evaluated and mitigated across the whole of their life cycle. Thus, ensuring that workers, consumers and environmental health have been appropriately protected, and facilitating social acceptance, regulatory control, and insurance activities related to nanotechnologies.
In order to reach all these goals, the project GUIDEnano was structured into 11 work packages (Figure 2) arranged by four main blocks: the Coordination block (WP1 and WP2), the Knowledge block subdivided into different technological building sub-blocks (WP3, WP4, WP5, WP6, WP7 and WP8) that generated the scientific input to the GUIDEnano Tool, the Software Development and Demonstration block (WP9 and WP10) that created the Tool itself and validated it in real life case studies, and the Dissemination, Standardization, and IPR block (WP11).
The role of the work packages of the Knowledge block was to develop strategies to make the fullest use of existing scientific information to harvest and/or predict the critical data needed for each step along the risk assessment process (i.e. release, environmental fate, exposure, hazard, risk assessment, and risk mitigation). This process started by the drafting of an initial strategy based on the state of the art at the start of the project. This allowed the identification of the most critical data gaps for the prediction of the data needed in each of these main steps. These were then addressed by tailored experimental and data collection efforts that allowed the refinement of the initially proposed strategies.
Project Results:
The main scientific and technical results of the project are summarized below.
WP3: RELEASE ASSESSMENT
The main objective of this WP was to generate and validate strategies to identify and categorize the release processes that take place during the life cycle of a NM-enabled product, and assess potential release of NM during such processes. Apart from the case studies included in GUIDEnano, which included polymeric nanocomposites, antifouling paints, anti-slip and photocatalytic tiles, nano-enabled textiles, nanocellulose based coatings and bituminous road products (see Figure 3), this WP aimed at covering the most representative applications in the market as well as those nanomaterials with current higher production volumes.
Based on mass-flow diagrams describing the life cycle stages of nano-enabled products, WP3 identified the sources and release pathways of different nanomaterials (NMs, including TiO2, Ag, ZnO, MWCNT and Cu-based nanomaterials). These release pathways or release scenarios were the starting point of the GUIDEnano Tool aiming at delivering standardized formats and default NM release values from nano-enabled products into the different environmental compartments. Release scenarios are called Activity Cards (AC) in GUIDEnano Tool. An AC library with 160 activities has been created and implemented in GUIDEnano tool, in collaboration with WP4. From this list the user can select one or more AC and start the risk assessment process. This library covers release scenarios in different life cycle stages of nano-enabled products: 1) synthesis (e.g. flame spray pyrolysis), 2) manufacturing (e.g. dumping), 3) use (e.g. use of polymeric nanocomposites outdoors) and 4) end-of-life (e.g. incineration). These activities contain information relative to the release of NMs and waste containing NMs that is generated during different processes (default release values are expressed as mass fraction). This allows predicting amounts of NMs reaching the different environmental compartments (e.g. water), and link the release / exposure module with subsequent fate and toxicity in the GUIDEnano Tool. Such environmental release factors were defined from existing literature values and information coming from the industrial partners when possible. In absence of empirical data release was defined following the ECHA R.16 Guidance document and also from expert judgment.
--Experimental studies performed to reduce uncertainties in the prediction of NMs release--
A series of experiments were planned to reduce key uncertainties that lead to the prediction of NMs release taking into account the life cycle stages that are most likely to result in the transformation and/or to result in the release of NM from different nano-enabled products provided by the industrial partners in GUIDEnano. As a result, a series of nano-enabled products and exposure scenarios were evaluated (see Figure 3) by LEITAT and CEA, investigating different parameters such as NM concentration, crystalline phase or coating. Experiments were performed to: 1) understand which are the processes promoting release, 2) how to reduce such release, 3) release kinetics, 4) release forms.
The nano-enabled products evaluated are summarized below:
1. Photocatalytic tiles (TiO2) and anti-slip tiles (Al2O3 and SiO2) (TORRECID, CEA and LEITAT). Accelerated ageing and abrasion experiments were performed. Both tiles and released materials were studied. NMs were leached out during the water spray step between 500 h and 1000 h from the photocatalytic tiles as free NMs. The aged antislip tiles released more NMs because of the matrix degradation during ageing. A safer by design (SbD) strategy was proposed for photocatalytic tiles.
2. Antibacterial textiles (INOTEX and LEITAT). Textile samples from INOTEX with melamine microcapsules containing adsorbed Ag nanoparticles were studied. LEITAT performed the washing simulations. ICP-MS results clearly showed that Ag is progressively lost after 5 washing cycles (between 50 and 20% of the initial Ag). However, the addition of suitable industrial binders reduces substantially Ag release from textiles. A SbD strategy was proposed by using new silver sources in terms of coatings or morphologies.
3. Enhanced performance polymers (LATI, LEITAT and CEA). Polypropylene (PP) polymer samples with different crystal phase, size and concentrations of TiO2 NMs were aged in a climatic chamber. PP containing TiO2 pigments were partially degraded during the ageing process. Released materials were mainly polymer fragments with embedded TiO2 NMs, but also free TiO2 nanoparticles were observed. Degradation increased when the concentration of nanofiller increased. The use of rutile phase reduced the degradation effect. Additionally, end-of-life experiments (landfill and incineration) were performed. A SbD strategy was proposed by coating the TiO2 particles with a silica layer.
4. Antifouling paints (HEMPEL, LEITAT and CEA). Antifouling paints (GLOBIC and OLYMPIC series) applied on an alumina Taber substrate were abraded. It was clearly seen that Globic paint series released more particles than Olympic ones. Then, new Globic paint formulations containing ZnO nanoparticles with different coatings were studied. Leaching tests in different culture media were performed to estimate the Zn and Cu released to water. Moreover, accelerated ageing in a climatic chamber followed by an abrasion test were explored to simulate workers exposure during sanding.
5. Nanocellulose for food packaging (INNVENTIA and CEA). CEA successfully marked nanocellulose from INNVENTIA with Ag and Au nanoparticles. Then, abrasion tests using a Taber abrader instrument were performed. Results showed that labelling really helps to distinguish both materials. Release of this thin layer abraded showed that nanocellulose is not released as single fibers.
--Experimental studies to evaluate the efficacy of SbD strategies to reduce NM release--
WP3 provided support to the SbD activities of WP8 (Risk Management), by testing the solution proposed in terms of its efficiency in reducing NM release and in maintaining the intended functionality of the NM in the product. Three different strategies were evaluated:
1. Ceramic tiles (TORRECID): physically adsorbed TiO2 on tile surfaces was substituted by a frit in order to improve the affinity between TiO2 NPs and reduce release. Two fritz sizes were tested and in one of the samples, almost no release of NMs was observed.
2. Antimicrobial textiles (INOTEX): Ag nanoparticles stabilized with two different coatings were explored. Moreover, silver nanowires (AgNW) with two different lengths were incorporated on the textiles and simulations were carried on. AgNW provided the best results.
3. Polymeric nanocomposites (LATI): The coverage of TiO2 particles with a SiO2 layer (TiO2@SiO2) coating was explored, and results revealed that polymer degradation was substantially reduced.
--Experimental studies performed to support the implementation of GUIDEnano Tool v2 by nanotech industry--
During the use of GUIDEnano Tool v2 by nanotech industry, initial predictions of risk based on worse case defaults lead to the identification of possible risks. In order to refine such risk assessments, release estimations by means of experimental tests were executed.
1. Polymeric nanocomposites containing MWCNT (LATI, CEA and LEITAT). Polyamide (PA66) samples containing glass fiber and different carbon nanofillers were aged by immersion in fuel simulant. The experiments revealed that release of MWCNT did not occur during this solvent contact scenario. Additionally, landfill and incineration experiments (end of life) were performed.
2. Photocatalytic bituminous mixture (Servià Cantó and LEITAT). Road samples (bitumen and coarse stones) impregnated with a TiO2 dispersion on water/resin were prepared by Servià Cantò. An accelerated weathering ageing on the climatic chamber was carried out. The released material obtained from the runoff waters indicated a higher release rate at the beginning of the experiment. Moreover, bitumen oxidation was observed over time due to UV exposure, which contributed to the road degradation (surface oxidation). Additionally, a wheel tracking assay was performed on the aged samples.
3. Antifouling paints (HEMPEL, LEITAT and CEA). Weathering plus abrasion and leaching (test in different culture media) experiments were performed over new formulated GLOBIC paints with nanoparticulated ZnO with different stabilizers.
--Main conclusions derived from the experimental studies--
No NMs release was found during abrasion of the antislip tiles containing Al2O3, paper film containing nanocellulose and polymeric composites with embedded MWCNT. Regarding the photocatalytic coatings applied on roads (TiO2), NMs were progressively removed from the surface, promoted by oxidation of bituminous compounds due to UV radiation. Interestingly, NMs release was successfully reduced by the application of safe-by-design strategies on three different case studies: photocatalytic tiles (TiO2), polymeric nanocomposites with TiO2 and textiles with Ag. These strategies consisted in modifying the interaction between matrix-nanomaterials, modifying the surface properties of the NMs and modifying the morphology of the NMs to improve adhesion on surfaces.
WP4: EXPOSURE ASSESSMENT
The main objective of WP4 was the development of models and guidance on (human) exposure assessment for the various stages of NM-enabled product value chains (life cycle). The human exposure assessment quantifies the air concentration of Nano Objects and their Agglomerates and Aggregates (NOAA) for nanorelated activities of workers and consumers by using available release/exposure measurement data, libraries and/or models for a wide variety of exposure scenarios, and guides the user of the GUIDEnano Tool to the available exposure data (in libraries) or to the appropriate exposure assessment model in the absence of suitable measured data.
An activity card library, containing around 150 activities, was built with associated worse case material release rates. These release rates are then automatically processed in a nano-specific dispersion model resulting into a worst case estimate of the inhalation exposure.
In addition to the activity card library, exposure scenario information from ongoing and finished FP7 projects (e.g. Nanomicex, Sanowork, Nanodevice, MARINA, SUN, NanoReg, GUIDEnano) was collected using a modification (adapted to the GUIDEnano approach) of the MARINA exposure scenario template. The resulting GUIDEnano library contains over 200 exposure scenarios.
A quality, similarity and relevance scoring system were developed to rate the different information sources as to their analogy to the user’s scenario.
In addition, the tool includes a mechanistic mass based model recognised under REACH: the Advanced REACH Tool (ART). For testing the performance of ART for NM scenarios, high quality exposure scenarios were selected and run in ART. This performance check included metric conversion methodology, analyses of nano-exposure measurements and finally the model performance check, which was designed to gain knowledge on the applicability of certain models for the use within nano-exposure assessment and thus for implementation in the GUIDEnano Tool.
Number count exposure data collected in standardized circumstances were converted to mass concentrations in order to be comparable to the model outputs. Statistical analyses were performed to examine correlation between model estimates and converted mass concentrations. Furthermore, model performance was evaluated based on the uncertainty given by the developers of the ART model.
Exposure measurement data were generated for the GUIDEnano case studies in order to refine the exposure scenarios mentioned above. Measurements were collected using the following direct-reading instruments: Condensation Particle Counter (CPC), NanoTracer, DiscMini, Fast Mobile Particle Sizer, elemental carbon (handling of CNT) and filter samples of airborne particles for SEM/EDX analysis. These measurement results gave good insight in the exposure levels during several activities in the value chain of the GUIDEnano case studies and were used to further validate the GUIDEnano model. Chamber experiments (under well controlled conditions) were also performed to simulate the scenarios of the case studies in the absence of workplace measurements.
The final exposure workflow of the GUIDEnano Tool compiles all these developments and consists of:
1. The user starts with selecting an activity card describing the scenario of interest, or by defining a scenario themselves without the use of an activity card.
2. The activity cards include a release rate for the scenario which is a default worst case estimate, or in case the user has more specific data, the default can be overruled by the user.
3. The release rate is automatically processed in the dispersion model resulting into a worst case estimate of the exposure, or in a realistic estimate when user’s release data is used.
4. Afterwards, the tool offers the user 4 different options to continue with the exposure scenario, namely: a) use this exposure estimate for the risk assessment; b) overrule this exposure estimate with field measurement data collected during the assessed scenario; c) overrule the exposure estimate by reading across exposure data from the scenario library or other comparable exposure data identified in literature. For the latter option a read across method based on similarity, relevance and quality was developed within GUIDEnano which determines how comparable data from literature is with the assessed scenario; d) overrule the exposure estimate by using a different exposure model estimate from ART (powder and abrasive scenarios), Consexpo (liquid scenarios), or Consexpo nano (spray scenarios).
WP5: ENVIRONMENTAL FATE
The main objective of this WP was to generate strategies to understand how NMs behave in natural systems including the critical transformation reactions. Several key questions were addressed: (i) How do NM properties and their nanoscale features affect their behavior and interactions with other environmentally relevant parameters, i.e. which property-fate relationships are crucial for fate prediction? (ii) What transformations are likely to occur in natural systems? (iii) How do the transformations affect the NM’s fate? These questions were quantitatively addressed to develop a conceptual fate model framework (Figure 5) focused on NM fate and behavior for implementation into the GUIDEnano Tool, and parameterized using available literature or by obtaining experimental results when data gaps were identified.
The integrated exposure model that was proposed for the prediction of the environmental fate of NMs in the various natural and man-made compartments had the kinetic nature of the NM fate processes as a central endpoint. A semi-mechanistic approach was used, with a minimum number of fate descriptors for the NM. In general, environmental matrix interactions depend on NM properties and relevant environmental properties, such as organic and inorganic matter type and concentration, as well as ionic strength and the presence of mono- or divalent ions. The fate descriptors were detailed for the following compartments: wastewater treatment plant (WWTP), water, soil and subsurface, and for the following transformations: heteroaggregation, sedimentation and sulfidation. The time-dependency of chemical species concentrations is an essential feature of this model, because it serves to link exposure scenarios with hazards that change over time.
The main achievements attained are described below for each environmental compartment addressed during the project.
--Main achievements related to WWTP –
1. A model was developed to predict partitioning of metals amongst sludge and effluent. Parameters are residence time, total suspended solids, and the NM/sludge partitioning coefficient at steady state (Kd).
2. A database was constructed from literature values suggesting that Kd can be related to NM size and the Hamaker constant.
3. WWTP microcosms were run using Ag NM, confirming the size dependence and lack of aggregation in WWTP. Neoformation of small AgNP that remain suspended was also found.
4. Kinetic batch attachment tests and sedimentation tests using WWTP confirmed the size dependence and effect of TSS. Lack of effects of coating, shear forces or ionic strength was found.
5. The final model predicts the mass and speciation of NM that ends up in soils AND freshwater as a function of size and Hamaker constants.
6. This knowledge is applicable in a safer-by-design context, e.g. to avoid emission of NMs to freshwaters.
--Main achievements related to the aquatic compartment—
1. Dissolution, heteroaggregation and sedimentation experiments were performed to address the main data gaps identified regarding fate of nanomaterials in the aquatic compartment. Several CuO, ZnO and Ag NMs with different manufactured coatings and sizes, and different water types (different composition and types of organic and inorganic matter) showed that the dissolution of the NMs is not significant and independent of the water composition, the manufactured coating of the NM and the size of the NM.
2. Heteroaggregation and sedimentation experiments confirmed that these processes depend on the presence of organic matter, but not on the water composition, manufactured coating, or size of the NM.
3. Several databases were constructed from literature values and experimental data obtained within the project containing physicochemical parameters of numerous freshwaters that can be found in Europe, properties of natural organic and inorganic colloids, and properties of NMs and respective transformations rates in water.
4. Statistical analysis of these databases confirmed the experimental results of the tests conducted within the project: organic matter properties do affect heteroaggregation and sedimentation, but the other properties investigated, ie., manufactured coating, size and chemical composition, do not.
5. A model was developed to predict the speciation of the NMs in the aquatic system. This model includes heteroaggregation, sedimentation, and transport along the river. The critical parameters of this model are natural organic and inorganic matter properties, and attachment efficiency. The final model predicts the speciation of the NMs discretized in size bins in the aquatic system as a function of the attachment efficiencies between the NMs and the natural organic matter.
--Main achievements related to the soil compartment—
1. A model was built where the pore-water and solid concentration of NMs in soils can be predicted based on easily measurable soil parameters such as texture, packing density, rainfall intensity, and attachment, detachment rates of NMs.
2. The model was refined further to relate attachment rates to the attachment efficiency for a specific NM – soil combination.
3. A database of 503 attachment efficiencies was built, but first statistical analysis did not reveal a straightforward relation between soil/NM properties and the attachment efficiency.
4. Experiments did show a poor mobility of larger NM compared to smaller NM of the same type, in the same soil.
--Main achievements related to the subsurface (or groundwater) compartment—
1. The model of NM reactive transport in groundwater was developed together with a database containing the model parameters. The performance of the model was evaluated using the GUIDEnano case-study, nZVI field application for groundwater remediation.
WP6: HAZARD ASSESSMENT
The main work of this WP was developing a strategy for predicting the ecotoxicological and human health hazard of the exposure-relevant NM forms released into exposure situations throughout the lifecycle of NM-enabled products.
--Development of a hazard assessment strategy—
The eco- and human toxicologists worked together to develop a hazard assessment strategy to estimate safety limit values making the fullest use of existing information while allowing prediction of hazard on the basis of different levels of data availability (each with an associated level of uncertainty reflecting the richness and quality of data available). The final hazard assessment strategy developed in GUIDEnano is presented in Figure 6. Existing OEL, DNEL or PNEC values for the material under evaluation will be used, if these are available. Otherwise, generic highly conservative thresholds can be used. When necessary, these can be refined based on available toxicity studies. The strategy mostly relies on information from studies following harmonized testing guidelines such as OECD and/or ISO, but is designed to also make use of ‘other non-standard’ studies and toxicity information. When assessing already existing individual toxicity studies from literature the hazard assessment strategy involves the establishment of scores to inform on quality (i.e. how good and reliable a study and its reporting is), relevance (i.e. how relevant the NM study is for the respective environmental compartment or human pathway/endpoint) and similarity (i.e. how well does the NM exposure in the study to be used reflect the exposure relevant form of nanomaterial which is being assessed). These scores are used to select studies that can be included in the process to derive safety limit values. In addition, the similarity score is used to introduce a ‘dissimilarity’ uncertainty factor.
--Evaluation of the role of nanomaterial coating on toxicity--
Hypotheses-driven experiments (different cores and coatings) were performed to evaluate the assumptions identified as most critical to reduce the most prominent uncertainties (e.g. from read across) in the hazard assessment process. To test the influence of the core material and the different coatings a base set of three different core materials (TiO2, CeO and Ag) each with three different coatings (citrate, PEG and an hydrophobic coating: DDPA in the case of TiO2, CeO and an oleylamine in the case of Ag) was selected for testing in a wide range of in vivo and in vitro test systems. No consistent trends were observed for the effects of coatings. These effects depended on the core material and the experimental test.
--Hazard characterization of the materials of the GUIDEnano case studies—
The nanomaterials of several of the project case studies were evaluated to allow the refinement of the hazard assessment when these case studies were evaluated by the industrial partners using the GUIDEnano Tool. The results of these studies are summarized below:
1. Antifouling paints (HEMPEL): Single species tests with selected representative standard bacterial (Pseudomonas putida), algal (Raphidocelis subcapitata) and daphnia (Daphnia magna) species were performed with the single components of the paints (micro CuO, Cu pirythione and ZnO; or nano ZnO). In addition, efficacy testing of the painted panels (with all the different paint types) was performed under controlled laboratory conditions as well as natural conditions in the river Thames. In addition, the bacterium Psedudomonas putida was exposed to release waters from the paint panels and none of these waters caused toxicity. Similarly, Daphnia were exposed to the releases from the paint panels in Daphnia culture medium. The reduction of ZnO particle size (micro to nano) helped to mitigate the release of Cu to the Daphnia magna medium and did not enhance the toxicity of the Globic paint to this specie.
ZnO NPs were also doped with Mn or Co (performed by DEI). These doped NPs did not increase the in vitro toxicity in fish cell lines.
2. Ceramics (TORRECID): TiO2 NPs from TORRECID had low toxicity in fish cell lines and Daphnia magna. In addition, the toxicity of the liquid dispersions and their respective dispersants to three bacterial species was tested under illumination and in the dark. Toxicity increased under light conditions. Clear conclusions on the toxicity of the NM are challenged by the fact that dispersants alone already caused some bacterial toxicity.
3. House-hold cleaning agent (NSER): In vitro, silver doped and undoped TiO2 NPs they did not induce cytotoxicity, immunotoxicity, genotoxicity nor toxicity in THP-1 lung macrophages and 16HBE lung epithelial cells and on the intestinal membrane model, although an increase of ROS production was observed in the latter model. In rodent intratracheal aspiration studies, they also showed very low toxicity, however, both NPs persisted in the mouse lungs up to one month after exposure, and inflammation and systemic genotoxicity were observed in the case of undoped NPs.
4. Photocatalytic hot bituminous mixture (Servià Cantó): Cytotoxicity and immunotoxicity were induced in vitro by the mixture (resin + TiO2 NP) in differentiated macrophages at the highest concentration tested. In contrast, exposure to the mixture or the individual components caused no genotoxicity in vitro and in vivo, no toxicity in the intestinal membrane model, and no in vivo immunotoxic effects. However, TiO2 NPs alone persisted longer in the mouse lungs than when they were exposed in combination with the resins.
5. Nanocelluloses (INNVENTIA): No cytotoxic effects were associated with the in vitro exposure to unmodified or surface-modified NFCs, whereas the observed inflammatory response to NFC might be driven by the material surface chemistry.
--Evaluation of efficacy of safer-by-design approaches in terms of hazard—
A number of experimental studies were performed in support of WP8’s safer-by-design (SbD) approaches (see Table 1).
From the human hazard point of view, the model Ag NPs showed no clear size dependent toxicity nor differences in Ag ion release in cell culture medium after 24 h. The application of PVP-coating and the oxide passivation layer (AgO) did not succeed in reducing the toxicity of the pristine NPs.
In the ecotoxicity studies, with different aquatic and terrestrial species, an increase in Ag NP size reduced toxicity and bioaccumulation, sulfidation of metallic AgNPs to Ag2S also decreased toxicity. On the other hand, no consistent results among different experimental species and test set-ups were obtained for AgO and Ag-PVP NPs. The Ag microcapsules provided by INOTEX were consistently more toxic to the different bacteria strains than the MSA- and TA-modified Ag NPs.
--Evaluation of toxicologically-relevant interactions of NM with other coexisting substances—
The purpose of this task was to evaluate how co-exposures with other hazardous components present in the NM-enabled product matrix or environmental pollutants could result in changes in toxicity of the NM or coexisting substances. The following type of scenarios were addressed:
1) Organic compounds of toxicological concern that are present in the nano-enabled product matrix. We tested the effects of three NMs from the case-studies containing other coexisting substances: antifouling paints (Hempel), house-hold cleaning agent (NSER), photocatalytic hot bituminous mixture (Servià Cantó). See description of the results in the section ‘Hazard characterization of the materials of the GUIDEnano case studies’.
2) Ubiquitous pollutants that can coexist in aquatic media such as endocrine disruptors and dioxin-like compounds, in combination with Ag, CeO2 and TiO2 nanoparticles. Some interactions were identified, which in part were possibly due to the adsorption of model organic pollutants on the nanoparticles surface.
3) Combination of different nanomaterials at low (non-toxic) concentrations. In vitro cytotoxicity assays with a hepatoma fish cell line co-exposed to different concentrations (from non-toxic to toxic) of Cu NPs and a non-toxic concentration of ZnO NPs were performed. Results in vitro indicated that the presence of non-toxic concentrations of ZnO NPs produced an increase in the toxicity of the Cu NPs and that this effect was produced by the NP and not by the Zn ions released. The co-exposure of Cu and ZnO NPs both at non-toxic concentrations also produced an acute toxic effect to fish.
WP7: RISK ASSESSMENT
The main goal of this work package was to develop a strategy for risk assessment of release- and exposure-relevant NMs in NM-enabled products throughout the various product life-cycle stages. This risk assessment strategy was incorporated in the interactive web-based GUIDEnano tool and was evaluated with hypothetical and real case studies within the project.
The initial decision flow for risk assessment incorporated in the GUIDEnano tool is presented in Figure 6. The safety limit value is comparable to the Derived No Effect Level (DNEL) for human health and Predicted No Effect Concentration (PNEC) for environment according to the REACH regulation.
Summary of the steps to derive a safety limit value:
1. Select hazard studies with associated effect levels (NOAEL, LOAEL, BMD, etc)
2. Determine modification/assessment factor for each effect level
3. Derive safety limit value by applying the assessment factors for each effect level (including a factor for dissimilarity)
4. Derive overall safety limit value per endpoint
5. Risk assessment: compare safety limit value with corresponding exposure level
The required factors (step 2) were listed and for each factor the purpose for application and the value are included. The risk assessment in GUIDEnano Tool v3 is deterministic, but some information is provided to the user to inform on the sources of uncertainty for the hazard limits derivation. For each assessment factor, it is indicated if it represents modification, uncertainty or variability. This information is needed to determine the possibility for reduction of the uncertainty of the safety limit value.
An output report has been designed and generated by WP7 together with the tool builders. This output report consists of a detailed background report with all information generated by the Tool based on the input of the user. This will be provided to the user after using the Tool, together with an executive summary of the risk assessment result (probability of risk) and proposed follow up actions (reduction of uncertainty, mitigation of risk by for instance safe by design strategies).
Case studies reported in the literature or hypothetical were used to evaluate the version 2 of the Tool. Feedback from this evaluation and feedback from stakeholders (e.g. industry, (re)insurance communities) obtained in dissemination events and via tailored questionnaires was used in the updates towards version 3. WP7 also monitored to what extent the industrial partners of the project were able to correctly use the GUIDEnano Tool during the evaluation of the project case studies. The specific questions that were addressed during these evaluations were the following: are the correct data used? Are the data inserted into the correct parameter fields of the tool? Are the relevant modules used for evaluation of the NM and NM-enabled product? Are the correct exposure tools and hazard studies used for the evaluation? Is the tool used as anticipated? This evaluation identified some issues, but the conclusion is that they can be solved by the availability of a manual and a more user-friendly version.
The GUIDEnano Tool was also evaluated in comparison to other existing tools (control banding tools: Stoffenmanager, Nanosafer, Nanotool, ANSES; Risk prioritization tools: Swiss Precautionary Matrix, NanoRiskCat, decision support tool; Weight-of-evidence approaches; Other: Licara NanoScan and ECETOC-TRA; MARINA framework, IATA, SCENIHR, CPM model, Probabilistic models: Simplebox4Nano), and the main advantages identified are the following (more details can be found in D7.5):
1. It is a complete tool, combining both hazard and exposure assessment and covering risks for workers, consumers and environment.
2. The tool is not limited to specific activities or exposure scenario’s and is flexible according to the users interests and focus.
3. The tool can cover the whole life cycle of a NM, from synthesis of the NM to the end-of-life phase including recycling. The GUIDEnano tool takes into account the changes in properties of the NM throughout the life cycle.
4. The tool integrates risk assessment and risk management, and specifies uncertainties.
5. The tool results in a quantitative risk assessment.
6. The tool is not for screening of risks or prioritization, but it supports decision-making. Decision-making can be performed for each scenario separately, without the need for comparison to other scenarios.
7. The tool matches with existing regulatory accepted risk assessment methods. For example: the hazard strategy and read across/ similarity procedures are strongly inspired by REACH.
WP8: RISK MANAGEMENT
Work package 8 aimed to propose, develop and validate risks mitigation measures (RMM) to reduce the potential risks identified through the risk assessment provided by the web-based Guidance Tool GUIDEnano. In such a way the final user, can select the most appropriate RMM allowing to control the risks highlighted and decrease them to an acceptable level, making the whole process safer. Among possible RMM, safer-by-design (SbD), occupational exposure control and advanced waste management strategies, were evaluated within the context of GUIDEnano case studies.
--Main achievements related to safer-by-design strategies--
Safer-by-design strategies were proposed taking into account the case studies and the NM employed and focusing on relevant endpoints and effects/risks to mitigate. SbD strategies were intended to:
1. Re-design relevant physicochemical properties of NM to mitigate their hazardous potential, while maintaining their characteristic functionality within the NM enabled product,
2. Avoid or reduce the release of NM during different life cycle stages of the nano-enabled products by improving compatibility between NM and matrix, to lower the possibility of environmental and/or human exposure to NM,
3. Avoid or reduce the environmental and/or human exposure to NM by designing and synthesizing less reactive and/or less persistent NM.
A set of SbD NM were synthesized at lab-scale level with targeted modifications of relevant physico-chemical properties and were provided to the different WPs to be evaluated for specific endpoints/ functionalities. For selected case studies, the resulting SbD NMs were implemented, namely in the case studies for TORR, LATI and INOTEX:
1. TORR modified the composition of TiO2 photocatalytic coating by developing a SbD approach aimed to lower the eventual NM release. Novel coating made up of TiO2 NMs and frit NMs were developed. The possible reduction of the NM release was tested through ageing/release experiment (WP3).
2. LATI implemented SbD NM by the substitution of TiO2 NM with SiO2 coated TiO2 NM as nanofiller, to suppress the photodegradation of polymeric nanocomposites and to improve their mechanical properties. The efficacy of this strategy was evaluated by WP3.
3. For the textile case study, different SbD Ag NMs were synthesized by Plasmachem (Ag coated with tannic acid, Ag coated with mercaptosuccinic acid) and VHIR (Ag nanowires with two different sizes) and delivered to INOTEX to functionalize textile samples providing them antibacterial properties. The SbD strategies were focused on a better compatibilization of NM within the matrix in order to avoid NM release to the human and environmental compartment during the use phase of the nanoenabled product. WP3 evaluated the efficacy of this strategy by means of “Washing” release experiments.
--Main achievements related to occupational exposure control measures—
One of the main achievements was the evaluation of the effectiveness of the personal protective equipment (PPEs) commonly employed by the industrial partners involved in GUIDEnano, with the objective to obtain for each of them a nominal protection factor (NPF) against NMs. The NPF of different PPEs have been determined, modified and validated using standard protocols available for bulk materials. Depending on the nature of the NM tested, two test protocols were adopted:
• a static test protocol to evaluate the NPF of PPEs against metal oxide NMs, which are considered potentially hazardous materials. These tests were performed under simulated conditions and using mannequins in substitution to individuals,
• a dynamic tests protocol to evaluate the NPF of PPEs against NaCl nanoparticles. NaCl is worldwide recognized as the conservative ‘Not hazardous’ test agent. PPEs were worn by different individual, thus conducting the ‘Practical Performance tests’ under the more realistic dynamic conditions.
Several types of masks, suits and gloves were investigated under simulated conditions performing static tests using different NM and at different concentrations (including also NM of different sizes). Results demonstrated that suits and masks, especially respiratory filters, offered a quite good NPF, sometimes slightly lower than the default value. Data collected showed unlike performance of the glove depending on NM type and concentration employed, therefore further tests need to be performed.
Full and half masks were tested under the dynamic test protocol. The credited NPF varied from 15 to 3000 (mostly due to their different fit to the facial geometry, being one of the mayor factors affecting the protection factor, more details in D8.2). Other alternative solution for respiratory protection (such as ventilated single use hoods) reached NPF of 65 000.
Regarding whole body protection, the PF for Protective suits varied from 1 (zero protection) for the overall non-woven up to 120,000 for the ventilated protective suit.
These investigations show that available PPEs can offer a wide range of protection levels and that the choice of the PPEs to be used depend on the Risk analysis and toxicity of the nanoparticle considered.
--Main achievements related to waste management strategies--
The work performed on the waste management strategies was aimed to reduce the NM environmental exposure (and exposure through the environment) by application of novel and known waste management strategies and by proposing waste reduction and potential implementation of recycling processes.
The seven GUIDEnano production processes/case studies were described in collaboration with the corresponding industrial partners (Hempel, Innventia, Inotex, Lati, Torrecid, Plasmachem and Servià Cantó). Then, for each case study, a production process diagram including a list of the nanowaste fractions generated, were depicted. Being the water containing NM one of the main waste fraction generated, different waste water treatments were selected according to their relevance for industry and their NM removal efficiency, these included settling, electrocoagulation, membrane distillation and advanced oxidation processes.
The efficiencies of the different strategies for NM removal were evaluated together with industrial partners and were collected in a compilation table, where information on “waste fractions”, “waste attributes” and “treatment process” was included. This information was incorporated into the GUIDEnano Tool.
--Incorporation of experimental and theoretical data on RMM into the GUIDEnano Tool--
Nano specific data collected from published literature and other EU funded projects, as well as data from the experimental evaluation performed by ITENE and HWELL on the effectiveness of PPEs was incorporated into the GUIDEnano Tool by:
1. The provision of protection or effectiveness factors for exposure engineering controls. The ECEL database was adapted to include nano-specific information and to allow its incorporation into the GUIDEnano Tool.
2. The provision of effectiveness factors for PPEs.
3. The provision of removal efficiency for different waste treatments.
WP9: TOOL DEVELOPMENT
The main objective of this WP was to develop the web-based tool. The design of the tool: Structure, flow, connections of all the components of the risk assessment (exposure, fate and hazard) and risk management strategies, is the result of a team work of all the technical WP experts in the different scientific areas (WP3-WP8) and the software specialists.
Three versions of the GUIDEnano Tool were delivered during the project.
1. GUIDEnano Tool v1 was released to consortium in the 18th month meeting (May 2015). In v1 the focus was on implementing the main structure of the tool in an object-oriented manner. First, class-diagrams where developed together with the experts for each individual wp. Next, these wp class-diagrams where merged into one single GUIDEnano class diagram, identifying overlap and harmonizing nomenclature. Relevant class-attributes (properties) where identified and assigned to the defined classes. In parallel, v1 of the application framework was developed, allowing online usage of the tool under development. Finally, v1 allowed the user to describe the relevant nanomaterial forms and identify the potential hazard hotspots during the life cycle of a nanomaterial/ nano-enabled product due to related activities and potential release(s).
2. GUIDEnano Tool v2 was released to consortium at the end of April 2016. In v2 the focus was on the implementation of the ‘behavior’ of the identified classes, like: rules, decision trees, algorithms. Over a hundred toxicity study classes covering both human and eco hazard were incorporated. The knowledge implemented in v2 allowed users not just to identify but also to quantify the risk of certain prioritized hotspots. This version was the basis for the internal evaluations (see WP7 and WP10).
3. GUIDEnano Tool v3 (Figure 8) was released at the Final consortium meeting. First, the feedback and related issues as a result of the evaluation were taken into account. Special focus in v3 was the improvement of the kinetic fate module, allowing now to predict the fate of nanoparticles per size-bin. Also, a first implementation of nanomaterial similarity for the inhalation hazard endpoint was built in.
The tool has been built on a modular basis which will be easy to update in the future.
WP10: VALIDATION OF THE GUIDENANO TOOL IN REAL CASE STUDIES
Industrial partners used the GUIDEnano Tool version 2 to evaluate the risks for their case study. During this process, when needed, they received support from the experts in each part (WPs 3 to 9).
The high potential of the Tool was well recognized during this evaluation, although the current version was not considered to be sufficiently user-friendly. Another main limitation that some industrial partners faced during the assessment process was the reluctance of their suppliers to provide characterisation data for the NMs. However, the main message to highlight about GUIDEnano Tool is that it contains all the complexity and components needed for assessing human and environmental risks of nanomaterials and nano-enabled products in all their life cycle stages. Furthermore, it is able to propose risk mitigation measures in case of identification of risks. Making something complex into a user-friendly version is the least problem that we face.
Potential Impact:
The Commission communications towards a European strategy for nanotechnology listed actions to support a high level of public health, safety, environmental and consumer protection including: (i) to identify and address safety concerns (real or perceived) at the earliest possible stage, (ii) to reinforce support for the integration of health, environmental, risk and other related aspects into R&D activities together with specific studies, (iii) to support the generation of data on toxicology and ecotoxicology (including dose-response data) and evaluate potential human and environmental exposure, (iv) to promote the adjustment, if necessary, of risk assessment procedures to take into account the particular issues associated with nanotechnology applications, (v) and to promote the integration of assessment of risk to human health, the environment, consumers and workers at all stages of the life cycle of the technology.
GUIDEnano was designed to guide the users (Industry, consultants, R&D staff, society) to assess the risks of any nano-enabled products at any of their life cycle stages. The ultimate goal of the GUIDEnano Tool is to assist both industry and society to ensure the safety of nano-enabled products considering all the potential release materials along the product life cycle, and their ultimate fate. Furthermore, the release assessment contributed to the industrial development of safer products by tailoring ENM properties and modifying matrix – NM interactions in order to reduce exposure.
GUIDEnano is a complete tool, which combines both hazard assessment and exposure assessment and covers risks for workers, consumers and environment. It takes into account different exposure routes and durations, and different endpoints of toxicity. The characteristics of NMs and corresponding potential risks can vary dependent on the life cycle stage, exposure route and the system it is in (human, environmental), which are all taken into account in the GUIDEnano tool.
Activities (exposure scenarios) can be created in the tool. This means that the tool is not limited to specific activities or exposure scenarios and is flexible according to the users interests and focus.
The tool involves the whole life cycle of a NM, from synthesis of the NM to the end-of-life phase including recycling. Most data available are based on pristine NMs, however, at later stages of the life cycle human or the environment can be expose to processed (e.g. coated) or aged NMs (recycling). The GUIDEnano Tool takes these changes in properties of the NM throughout the life cycle into account.
The Tool integrates risk assessment and risk management, and specifies uncertainties. Based on the integration of all these aspects, the uncertainties can be diminished and risk mitigation strategies (safe by design, exposure control measures, waste management) are recommended in the Tool, in an iterative process.
The project has played an active and important role in the refinement of the human and environmental hazard strategy for risk assessment, which includes a similarity algorithm for read across purposes. In addition, the gained expertise on developing/ modifying hazard and exposure models for risk assessment of nanomaterials will be further developed in running and future projects (e.g. the H2020 NANOFASE, calibrate, GRACIOUS).
The Tool results in a quantitative risk assessment, allowing a justified assessment for each scenario. Based on hazard assessment, and taking into account similarity and quality of data, a Safety Limit Value is derived and compared to exposure concentrations, resulting in a ratio relating to a probability of risk. Together with the uncertainty relating to this risk value, it provides a founded view of the probability of risk and which actions may be taken to reduce the risk, if necessary.
The Tool is not for screening of risks or prioritization, but it supports decision-making. Decision-making can be performed for each scenario separately, without the need for comparison to other scenarios.
The Tool matches with existing regulatory accepted risk assessment methods. For example: the hazard strategy and read across/ similarity procedures are strongly inspired by REACH. Also accepted hazard testing methods in the tool match with OECD approved methods
GUIDEnano tool will advise companies to invest in the research which contributes most to reduce the potential risks by applying risk mitigation measures or reducing uncertainties. GUIDEnano output report gives the user of the Tool an extended overview of the potential risk (including uncertainties) of their NM-enabled product. It also gives options to either reduce the risk and/ or the uncertainties.
Economic Impact
Economically, the impact the GUIDEnano Tool will have on the nano-enabled materials industry will be significant as more of the industrial stakeholders need to assess the risks associated with the production of such materials.
The time to market for new nano-enabled products and materials will shorten because industry is guided in a uniform, reproducible and testable way through all relevant steps of the risk assessment. The Risk Assessment framework in GUIDEnano is generic and therefore can also be applied for other substances related (future) risk assessment tools even outside the nano-knowledge domain.
The impact of the tool might be further increased by introducing specials, like an occupational version, consumer version or environmental version all using the same knowledgebase but with custom made user interfaces to enhance usability. This will increase the potential market for licensing the tool and allows differentiation in pricing.
The practical feedback from industrial partners is a significant contribution to the tool development in terms of user-friendliness and practical needs of different industrial sectors. The feedback of industrial partners is of paramount importance to increase the market success of the tool and academic partners have already worked with relevant WPs to increase user-friendliness and to avoid some bottlenecks in the wide adoption like confidentiality issues.
Impact on Regulations
GUIDEnano will help implement the EC communication Regulatory Aspect of Nanomaterials (COM (2008)36629 and COM (2012)57230) which calls for improvement in the knowledge of characterization, hazards, exposure, risk assessment and risk management of NM. The Tool matches with existing regulatory accepted risk assessment methods. For example: the hazard strategy and read across/ similarity procedures are strongly inspired by REACH. Also accepted hazard testing methods in the Tool match with OECD approved methods. This will help in easy implementation and future exploitation as a trusted tool for risk assessment of nanomaterial and nano-enabled products.
To maximize the impact of GUIDEnano, the consortium has been active in attending events and workshops to establish cooperation (aligning with their discussions and decisions) with international organization, such as OECD and ECHA, including the following:
OECD Working Party on Manufactured Nanomaterials, Expert Meeting on Categorization of Manufactured Nanomaterials (17-19 September 2014 Washington (USA)) Stimulus presentations: "Nanomaterial classification considerations for environmental fate" the GUIDEnano WP6 lead was asked by DG-Env to represent the EU delegation and, with Dr Iseult Lynch from NanoMILE, asked to present one of the Stimulus presentations in session 4 on Environmental fate implications on Categorisation and Risk Assessment. They presented not only the GUIDEnano and NanoMILE aspects, but summarised the relevant elements of all the NSC WG3 projects. Additionally D.Brouwer (TNO) and JM Navas (INIA) were invited to this expert meeting as respectively the Dutch and Spanish representative at the OECD Working Party on Manufactured Nanomaterials.
For ECHA’s Topical Scientific Workshop – Regulatory Challenges in Risk Assessment of Nanomaterials (23-24 October 2014, Helsinki, Finland) GUIDEnano representatives were invited onto the Scientific Steering committee for developing the event, present in the plenary sessions and sit on the panel in the discussion sessions. These brought together close to 200 experts in the field of risk assessment of nanomaterials representing academia, policy makers, industry and NGOs, to discuss how to address current challenges from the regulatory perspective which can be reflected and employed in the ongoing and future research topics on nanomaterials. The discussions were reinforced by information on recent developments and on risk assessment methodologies (including GUIDEnano’s) applied in chemicals management both within and outside the European Union.
Impact on Standardization
GUIDEnano utilised the nanoSTAIR approach which is a process and a platform to support standardization for nanotechnologies. GUIDEnano deliverables were all systematically checked by a standardization expert against a number of committees including (ISO/TC 24/SC 4, ISO/TC 201, ISO/TC 202, ISO/TC 209, ISO/TC 229/JWG 1, ISO/TC 229/JWG 2, ISO/TC 229/WG 3, ISO/TC 229/WG 4). No content or results of GUIDEnano were good candidates for further standardization process. In particular, GUIDEnano activities were mainly divided in two directions: Development of algorithms/ roles/ tables/ decision trees/ strategies to build up the RA tool and generating data to cover data gaps in different areas by using as far as possible standardized or well-established protocols and methods. Working together with the partner in charge with the task of standardization in GUIDEnano (DIN- German Institute for standardization) facilitated the identification of new protocols or new methodologies as potential candidates for going through a standardization process. Furthermore, the use of nanoSTAIR approach during the project was an opportunity for all the partners to get familiarized with it to apply it in their future work.
GUIDEnano was also very active in Nanosafety Cluster standardiazation subgroup. This led to the preparation of documents on standards and standardization in all projects related to nanotechnologies. Including reports containing a compendium of relevant committees, their standards and their current activities. These documents can be found published in the nanosafety cluster website (http://www.nanosafetycluster.eu/working-groups/7-dissemination-wg/standardization/how-to-bring-your-nanosafety-research-to-standards-a-comprehensive-set-of-guidance.html).
Dissemination and Exploitation
The project engaged various stakeholders to whom the results of the project were communicated to. The consortium was dedicated to to attend conferences, publish papers in peer reviewed journals, share news and updates of the project on a regular basis, during the lifetime of the project. While results were widely shared by several partners from the consortium at all the main conferences around the year, the main result of the project, GUIDEnano Tool, was not publically shown until the second year of the project. General information about GUIDEnano was initially disseminated by means of printed and digital media. In month 3 of the project the website was established with domain name (www.guidenano.eu) with general information about the project. Updates about the project, events, news, electronic format of printed media were all included on the website when ever available. In month 6 the project leaflet was produced. Printed versions were distributed at conferences, meetings and events whenever possible. An electronic version was also made available on the project website. An updated project leaflet was produced in month 30 with printed and an electronic version. Two newsletters were published during the project time. Both were made available on the project website and were distributed to stakeholders through the Nanosafety Cluster distribution channels.
Project videos were produced. The first one was a general video about the project and how the Tool helps the industries and nano-enabled products manufacturers to evaluate the associated risks. This video was released in anticipation of the Tool and to disseminate that it is functional and would be ready soon. The second video was more professionally made for wider distribution. Social media was also use to disseminate and communicate the project results. A twitter account was created and the consortium was given access to allow publication of news, events and updates about the project. The twitter feed is available on the project website. LinkedIn was also used as a platform for communication. The consortium was very active in disseminating the project results consistently.
More than a 100 oral presentation and posters were presented at European and international conferences covering all technical work packages. Five articles were published peer review journals with one currently under revision. In the pipeline, there are currently 2 articles submitted and several papers in the draft form for the different WPs. One patent was filed by CEA for methods of tagging and labelling nanocellulose for monitoring the release of the nanomaterials from products. Specific dissemination targeting stakeholders and regulators was also done to maximize the project impact and exposure.
Concerning the scientific publications in peer-review Journals: The main publishable outcomes came late during the project (as expected, looking at the DoW); therefore, publications are currently under preparation. The first year of the project was dedicated to build-up the structure of the Tool and the experimental work did not start until the second year. And the duration of some experiments also caused some delays in the generation of experimental data. Therefore, partners from the different WPs are currently working on writing the publications on their specific area. Furthermore, the revised and modified decision trees, algorithms, models, strategies will be soon published (e. g. Quality assessment Tool- submitted, similarity approach of GUIDEnano-ready for submission).
Showcasing the GUIDEnano Tool was crucial for its communication and pre-marketing but also for its development. Thanks to these public presentations, the Tool had various feedback sessions very useful for its further development but also greatly contributed to its diffusion among the targeted stakeholders and beyond.
The activities done to present the Tool to stakeholders can be summed up in two main types: general presentations and in-depth presentations. The former ones were often shorter and did not go into the technical details and functioning of the Tool. The aim was to present its most important features and its added-value for scientists and industries. These presentations were rather short and the public was less specialised around the risk assessment of nano-enabled products.
• Nanomaterial Safety Assessment Conference in Malaga
From the 7th to the 9th of February 2017, five large FP7 research projects (NANOSOLUTIONS, SUN, NanoMILE, GUIDEnano and eNanoMapper) jointly organized a conference in Malaga (Spain), that aimed at presenting the main results achieved in the course of the projects fostering a discussion about their impact in the nanosafety field and possibilities for future research programmes. The conference gathered consortium partners from the organizing projects, as well as representatives from other EU projects, industry, government, civil society and media.
• Joint Scientific Conference of ProSafe & OECD
From the 29th of November to the 1st of December 2016, a joint scientific conference of ProSafe & OECD took place at the OECD Conference Centre in Paris. During 3 days, researchers coordinating large European projects in the field of nanosafety and regulatory authorities such as the European Commission and the OECD met and presented their work done and their vision in the field.
• Nanomaterials: Industrial workshop on safe-by-design (Bilbao, 24-25 April, 2017)
• Towards safe-by-design (EuronanoForum, June 23rd, Malta, 2017)
More in-depth workshops/ seminars including step-by-step explanation of the Tool:
• Stakeholder workshop during NANOSAFE 2016
From the 7th to the 10th of November 2016, the fifth International conference nanoSAFE took place in Grenoble hosted by the CEA in the MINATEC. GUIDEnano had a strong presence to present its online Tool for risk assessment of nano-enabled products and organised on the 10th in the morning a stakeholder workshop inviting industrial and scientific partners to a presentation showcasing for the first time the interactive Tool.
• GUIDEnano Webinar: On the 8th of March 2017, LEITAT organised a webinar directed to insurance companies. With the support of Pinsent Mason, partner of the project, around 5 professionals from the insurance sector attended the webinar. During an extensive presentation about the rationale, features, modules and case studies, Gemma Janer from LEITAT presented the results of almost 4 years of research and development. The core of the presentation was articulated the modules of the Tool, being materials, activities, compartments, exposure, hazard and risk assessment and management. By showing the Tool itself, the insurance companies could see the current stage of development which was already fully functioning at that time.
The presentation was followed by a discussion with the audience guided by questions prepared by GUIDEnano team. It included the most interesting features for the audience and possible extensions currently missing that would be useful for the audience.
• Webinar for caLIBRAte risk assessment partners.
Exploitation
Exploitation of GUIDEnano results was a priority from the start of the project. In the first 6 months the consortium identified 20 potential exploitable results related to a number of partners. Most of these potential exploitable results were then considered results that are/ will be published or patented. However, the overall consensus was that the Tool was the main outcome with the most potential for successful exploitation. GUIDEnano Tool has many advantages over existing or otherwise developed risk assessment tools. These advantages include:
• Software more complete than the current competitors on the market.
• Generating valuable information for users.
• Software flexibility that allows easy implementation of new updates in any of the modules.
• Cost savings to the customer, when offered through SaaS, since users do not have to incur the cost of purchasing the software and installation, but only pay for accessing the service.
• As the tool is housed in a central server, all the data inserted from the different users will be used as feedback for the tool, contributing in the improvement on predictability of the different modules of GUIDEnano.
There are a number of options to exploit the Tool. This may be done through a basic license, premium license, license through “pay per use” or a free limited license. A preliminary study of the costs associated with updating the Tool to bring it closer to market ready status was conducted. At the current state the Tool is complex to use without training, therefore necessary steps needs to be taken to simplify its use for customers in order to gain market potential. Future exploitation of the tool also may include specific package software tailored for specific industries/ users/ communities e.g. textile, paints, etc. the tool may also be updated through the participation in new projects which will generate new knowledge that can be integrated into the tool to make it more complete.
After a first revision of the exploitation plan presented at the end of the project, LEITAT and THINKWORKS (TW) generated a more detailed plan to exploit the Tool. First of all, the IPR issues needed to be solved with an official written document and then the immediate steps needed to generate new versions of GUIDEnano Tool that we can commercialize in the near future. The first task is to work on getting GUIDEnano Tool v3 as a free accessible version simplifying what is needed to make it as user-friendly as possible. In the short –medium term the participation of LEITAT and, in some cases, also THINKWORKS in running or nearly starting projects (NANOFASE, caLIBRAte, GRACIOUS, NANOCOMMONS) will allow us to further implement and improve different modules of the Tool. And then, further developments will lead to more advanced versions of the Tool which can then be sale through licenses. Trainings and consultancy services are foreseen within the exploitation plan discussed for GUIDEnano Tool. Dissemination activities will continue in order to promote the Tool and get engagements with all the organizations/ communities/ researches. The first step is the use of the important dissemination platform of ECHA: The observatory for nanomaterials.
Furthermore, the work on safe-by-design that was initiated in GUIDEnano with some industrial partners will be continued in other projects to be able to consider patenting some of the results (NANOFASE, caLIBRAte).
List of Websites:
www.guidenano.eu
Project Coordinator: Socorro Vázquez (svazquez@leitat.org)
LEITAT Technological Center
C/ de la Innovació, 2
08225
Terrassa (Barcelona)
Spain
Current uncertainties on the safety of nano-enabled products need to be urgently and carefully addressed. Otherwise, public fears could end up blocking the benefits of nanotechnology. Sound scientific information must be generated to identify potential risks of nano-enabled products on human and ecosystems health, taking into consideration all stages of the life cycle of these products. Some web-based control banding tools are already available, but these mainly focus on the worksite and are mainly intended at the identification of hotspots rather than a complete risk assessment.
The recently finalized EU FP7 project GUIDEnano aimed to develop a methodology to address the human and environmental health risks of nano-enabled products, considering the whole product life cycle, i.e. synthesis of nanomaterials (NM), manufacturing of NM-enabled products, use, and end-of-life phase. The project consortium consisted of around 30 international partners, including universities, research institutes and industrial partners developing NM-enabled products.
The GUIDEnano consortium reviewed and structured the state of the art knowledge on the risk assessment of nanomaterials, and identified a series of gaps that were addressed by a series of experimental studies and comprehensive literature data analysis. The project incorporated as well 8 industrial case studies that were investigated in detail and were used to evaluate the performance of the Tool.
The main result of this 3.5-year effort is the GUIDEnano Tool, which incorporated in a structured-way all knowledge compiled/generated by the consortium in order to provide a quantitative human and environmental risk evaluation. Where needed, the Tool allows to assess how different risk management measures would modify the risk estimation, for example by providing the efficiency of methods for exposure reduction or by evaluating materials that are produced with the goal to be inherently safe(r) by design.
The correct implementation of this guidance ensures that the risks associated with a NM-enabled product, throughout its whole life cycle/ value chain, have been appropriately evaluated and mitigated to an acceptable level, according to the most recent knowledge at the time of implementation. The evaluation of a NM-enabled product using this Tool will also be useful for risk communication to regulators, insurance companies, and society.
Project Context and Objectives:
The main objective of GUIDEnano was to develop innovative methodologies to evaluate and manage human and environmental health risks of nano-enabled products, considering the whole product life cycle: synthesis of NM, manufacturing of NM-enabled products, use, and end-of-life phase (including recycling) (Figure 1). These developments were incorporated into an interactive web-based Guidance Tool, which guides the NM-enabled product developers (mainly industry) into the design and application of the most appropriate risk assessment & mitigation strategy for a specific product.
The specific goals of the project were the following:
1. To develop methodologies to evaluate the risks of a wide diversity of nano-enabled products on human and environmental health, throughout their life cycle.
2. To develop innovative solutions to reduce the identified risks. A wide range of risk mitigation strategies and guidance on the selection of the most appropriate measures for each scenario associated to an unacceptable risk will be provided.
3. To integrate the risk evaluation and mitigation strategies into the GUIDEnano Tool and to carry out an iterative process of performance testing, feedback and improvement steps to validate its suitability and applicability to real-case NM-enabled products, including a detailed plan for the hosting and maintenance of the GUIDEnano Tool after the life time of the project.
4. To efficiently communicate to consumers, regulators and insurance communities that, by following the GUIDEnano Tool, risks associated with an NM-enabled product have been adequately identified, evaluated and mitigated across the whole of their life cycle. Thus, ensuring that workers, consumers and environmental health have been appropriately protected, and facilitating social acceptance, regulatory control, and insurance activities related to nanotechnologies.
In order to reach all these goals, the project GUIDEnano was structured into 11 work packages (Figure 2) arranged by four main blocks: the Coordination block (WP1 and WP2), the Knowledge block subdivided into different technological building sub-blocks (WP3, WP4, WP5, WP6, WP7 and WP8) that generated the scientific input to the GUIDEnano Tool, the Software Development and Demonstration block (WP9 and WP10) that created the Tool itself and validated it in real life case studies, and the Dissemination, Standardization, and IPR block (WP11).
The role of the work packages of the Knowledge block was to develop strategies to make the fullest use of existing scientific information to harvest and/or predict the critical data needed for each step along the risk assessment process (i.e. release, environmental fate, exposure, hazard, risk assessment, and risk mitigation). This process started by the drafting of an initial strategy based on the state of the art at the start of the project. This allowed the identification of the most critical data gaps for the prediction of the data needed in each of these main steps. These were then addressed by tailored experimental and data collection efforts that allowed the refinement of the initially proposed strategies.
Project Results:
The main scientific and technical results of the project are summarized below.
WP3: RELEASE ASSESSMENT
The main objective of this WP was to generate and validate strategies to identify and categorize the release processes that take place during the life cycle of a NM-enabled product, and assess potential release of NM during such processes. Apart from the case studies included in GUIDEnano, which included polymeric nanocomposites, antifouling paints, anti-slip and photocatalytic tiles, nano-enabled textiles, nanocellulose based coatings and bituminous road products (see Figure 3), this WP aimed at covering the most representative applications in the market as well as those nanomaterials with current higher production volumes.
Based on mass-flow diagrams describing the life cycle stages of nano-enabled products, WP3 identified the sources and release pathways of different nanomaterials (NMs, including TiO2, Ag, ZnO, MWCNT and Cu-based nanomaterials). These release pathways or release scenarios were the starting point of the GUIDEnano Tool aiming at delivering standardized formats and default NM release values from nano-enabled products into the different environmental compartments. Release scenarios are called Activity Cards (AC) in GUIDEnano Tool. An AC library with 160 activities has been created and implemented in GUIDEnano tool, in collaboration with WP4. From this list the user can select one or more AC and start the risk assessment process. This library covers release scenarios in different life cycle stages of nano-enabled products: 1) synthesis (e.g. flame spray pyrolysis), 2) manufacturing (e.g. dumping), 3) use (e.g. use of polymeric nanocomposites outdoors) and 4) end-of-life (e.g. incineration). These activities contain information relative to the release of NMs and waste containing NMs that is generated during different processes (default release values are expressed as mass fraction). This allows predicting amounts of NMs reaching the different environmental compartments (e.g. water), and link the release / exposure module with subsequent fate and toxicity in the GUIDEnano Tool. Such environmental release factors were defined from existing literature values and information coming from the industrial partners when possible. In absence of empirical data release was defined following the ECHA R.16 Guidance document and also from expert judgment.
--Experimental studies performed to reduce uncertainties in the prediction of NMs release--
A series of experiments were planned to reduce key uncertainties that lead to the prediction of NMs release taking into account the life cycle stages that are most likely to result in the transformation and/or to result in the release of NM from different nano-enabled products provided by the industrial partners in GUIDEnano. As a result, a series of nano-enabled products and exposure scenarios were evaluated (see Figure 3) by LEITAT and CEA, investigating different parameters such as NM concentration, crystalline phase or coating. Experiments were performed to: 1) understand which are the processes promoting release, 2) how to reduce such release, 3) release kinetics, 4) release forms.
The nano-enabled products evaluated are summarized below:
1. Photocatalytic tiles (TiO2) and anti-slip tiles (Al2O3 and SiO2) (TORRECID, CEA and LEITAT). Accelerated ageing and abrasion experiments were performed. Both tiles and released materials were studied. NMs were leached out during the water spray step between 500 h and 1000 h from the photocatalytic tiles as free NMs. The aged antislip tiles released more NMs because of the matrix degradation during ageing. A safer by design (SbD) strategy was proposed for photocatalytic tiles.
2. Antibacterial textiles (INOTEX and LEITAT). Textile samples from INOTEX with melamine microcapsules containing adsorbed Ag nanoparticles were studied. LEITAT performed the washing simulations. ICP-MS results clearly showed that Ag is progressively lost after 5 washing cycles (between 50 and 20% of the initial Ag). However, the addition of suitable industrial binders reduces substantially Ag release from textiles. A SbD strategy was proposed by using new silver sources in terms of coatings or morphologies.
3. Enhanced performance polymers (LATI, LEITAT and CEA). Polypropylene (PP) polymer samples with different crystal phase, size and concentrations of TiO2 NMs were aged in a climatic chamber. PP containing TiO2 pigments were partially degraded during the ageing process. Released materials were mainly polymer fragments with embedded TiO2 NMs, but also free TiO2 nanoparticles were observed. Degradation increased when the concentration of nanofiller increased. The use of rutile phase reduced the degradation effect. Additionally, end-of-life experiments (landfill and incineration) were performed. A SbD strategy was proposed by coating the TiO2 particles with a silica layer.
4. Antifouling paints (HEMPEL, LEITAT and CEA). Antifouling paints (GLOBIC and OLYMPIC series) applied on an alumina Taber substrate were abraded. It was clearly seen that Globic paint series released more particles than Olympic ones. Then, new Globic paint formulations containing ZnO nanoparticles with different coatings were studied. Leaching tests in different culture media were performed to estimate the Zn and Cu released to water. Moreover, accelerated ageing in a climatic chamber followed by an abrasion test were explored to simulate workers exposure during sanding.
5. Nanocellulose for food packaging (INNVENTIA and CEA). CEA successfully marked nanocellulose from INNVENTIA with Ag and Au nanoparticles. Then, abrasion tests using a Taber abrader instrument were performed. Results showed that labelling really helps to distinguish both materials. Release of this thin layer abraded showed that nanocellulose is not released as single fibers.
--Experimental studies to evaluate the efficacy of SbD strategies to reduce NM release--
WP3 provided support to the SbD activities of WP8 (Risk Management), by testing the solution proposed in terms of its efficiency in reducing NM release and in maintaining the intended functionality of the NM in the product. Three different strategies were evaluated:
1. Ceramic tiles (TORRECID): physically adsorbed TiO2 on tile surfaces was substituted by a frit in order to improve the affinity between TiO2 NPs and reduce release. Two fritz sizes were tested and in one of the samples, almost no release of NMs was observed.
2. Antimicrobial textiles (INOTEX): Ag nanoparticles stabilized with two different coatings were explored. Moreover, silver nanowires (AgNW) with two different lengths were incorporated on the textiles and simulations were carried on. AgNW provided the best results.
3. Polymeric nanocomposites (LATI): The coverage of TiO2 particles with a SiO2 layer (TiO2@SiO2) coating was explored, and results revealed that polymer degradation was substantially reduced.
--Experimental studies performed to support the implementation of GUIDEnano Tool v2 by nanotech industry--
During the use of GUIDEnano Tool v2 by nanotech industry, initial predictions of risk based on worse case defaults lead to the identification of possible risks. In order to refine such risk assessments, release estimations by means of experimental tests were executed.
1. Polymeric nanocomposites containing MWCNT (LATI, CEA and LEITAT). Polyamide (PA66) samples containing glass fiber and different carbon nanofillers were aged by immersion in fuel simulant. The experiments revealed that release of MWCNT did not occur during this solvent contact scenario. Additionally, landfill and incineration experiments (end of life) were performed.
2. Photocatalytic bituminous mixture (Servià Cantó and LEITAT). Road samples (bitumen and coarse stones) impregnated with a TiO2 dispersion on water/resin were prepared by Servià Cantò. An accelerated weathering ageing on the climatic chamber was carried out. The released material obtained from the runoff waters indicated a higher release rate at the beginning of the experiment. Moreover, bitumen oxidation was observed over time due to UV exposure, which contributed to the road degradation (surface oxidation). Additionally, a wheel tracking assay was performed on the aged samples.
3. Antifouling paints (HEMPEL, LEITAT and CEA). Weathering plus abrasion and leaching (test in different culture media) experiments were performed over new formulated GLOBIC paints with nanoparticulated ZnO with different stabilizers.
--Main conclusions derived from the experimental studies--
No NMs release was found during abrasion of the antislip tiles containing Al2O3, paper film containing nanocellulose and polymeric composites with embedded MWCNT. Regarding the photocatalytic coatings applied on roads (TiO2), NMs were progressively removed from the surface, promoted by oxidation of bituminous compounds due to UV radiation. Interestingly, NMs release was successfully reduced by the application of safe-by-design strategies on three different case studies: photocatalytic tiles (TiO2), polymeric nanocomposites with TiO2 and textiles with Ag. These strategies consisted in modifying the interaction between matrix-nanomaterials, modifying the surface properties of the NMs and modifying the morphology of the NMs to improve adhesion on surfaces.
WP4: EXPOSURE ASSESSMENT
The main objective of WP4 was the development of models and guidance on (human) exposure assessment for the various stages of NM-enabled product value chains (life cycle). The human exposure assessment quantifies the air concentration of Nano Objects and their Agglomerates and Aggregates (NOAA) for nanorelated activities of workers and consumers by using available release/exposure measurement data, libraries and/or models for a wide variety of exposure scenarios, and guides the user of the GUIDEnano Tool to the available exposure data (in libraries) or to the appropriate exposure assessment model in the absence of suitable measured data.
An activity card library, containing around 150 activities, was built with associated worse case material release rates. These release rates are then automatically processed in a nano-specific dispersion model resulting into a worst case estimate of the inhalation exposure.
In addition to the activity card library, exposure scenario information from ongoing and finished FP7 projects (e.g. Nanomicex, Sanowork, Nanodevice, MARINA, SUN, NanoReg, GUIDEnano) was collected using a modification (adapted to the GUIDEnano approach) of the MARINA exposure scenario template. The resulting GUIDEnano library contains over 200 exposure scenarios.
A quality, similarity and relevance scoring system were developed to rate the different information sources as to their analogy to the user’s scenario.
In addition, the tool includes a mechanistic mass based model recognised under REACH: the Advanced REACH Tool (ART). For testing the performance of ART for NM scenarios, high quality exposure scenarios were selected and run in ART. This performance check included metric conversion methodology, analyses of nano-exposure measurements and finally the model performance check, which was designed to gain knowledge on the applicability of certain models for the use within nano-exposure assessment and thus for implementation in the GUIDEnano Tool.
Number count exposure data collected in standardized circumstances were converted to mass concentrations in order to be comparable to the model outputs. Statistical analyses were performed to examine correlation between model estimates and converted mass concentrations. Furthermore, model performance was evaluated based on the uncertainty given by the developers of the ART model.
Exposure measurement data were generated for the GUIDEnano case studies in order to refine the exposure scenarios mentioned above. Measurements were collected using the following direct-reading instruments: Condensation Particle Counter (CPC), NanoTracer, DiscMini, Fast Mobile Particle Sizer, elemental carbon (handling of CNT) and filter samples of airborne particles for SEM/EDX analysis. These measurement results gave good insight in the exposure levels during several activities in the value chain of the GUIDEnano case studies and were used to further validate the GUIDEnano model. Chamber experiments (under well controlled conditions) were also performed to simulate the scenarios of the case studies in the absence of workplace measurements.
The final exposure workflow of the GUIDEnano Tool compiles all these developments and consists of:
1. The user starts with selecting an activity card describing the scenario of interest, or by defining a scenario themselves without the use of an activity card.
2. The activity cards include a release rate for the scenario which is a default worst case estimate, or in case the user has more specific data, the default can be overruled by the user.
3. The release rate is automatically processed in the dispersion model resulting into a worst case estimate of the exposure, or in a realistic estimate when user’s release data is used.
4. Afterwards, the tool offers the user 4 different options to continue with the exposure scenario, namely: a) use this exposure estimate for the risk assessment; b) overrule this exposure estimate with field measurement data collected during the assessed scenario; c) overrule the exposure estimate by reading across exposure data from the scenario library or other comparable exposure data identified in literature. For the latter option a read across method based on similarity, relevance and quality was developed within GUIDEnano which determines how comparable data from literature is with the assessed scenario; d) overrule the exposure estimate by using a different exposure model estimate from ART (powder and abrasive scenarios), Consexpo (liquid scenarios), or Consexpo nano (spray scenarios).
WP5: ENVIRONMENTAL FATE
The main objective of this WP was to generate strategies to understand how NMs behave in natural systems including the critical transformation reactions. Several key questions were addressed: (i) How do NM properties and their nanoscale features affect their behavior and interactions with other environmentally relevant parameters, i.e. which property-fate relationships are crucial for fate prediction? (ii) What transformations are likely to occur in natural systems? (iii) How do the transformations affect the NM’s fate? These questions were quantitatively addressed to develop a conceptual fate model framework (Figure 5) focused on NM fate and behavior for implementation into the GUIDEnano Tool, and parameterized using available literature or by obtaining experimental results when data gaps were identified.
The integrated exposure model that was proposed for the prediction of the environmental fate of NMs in the various natural and man-made compartments had the kinetic nature of the NM fate processes as a central endpoint. A semi-mechanistic approach was used, with a minimum number of fate descriptors for the NM. In general, environmental matrix interactions depend on NM properties and relevant environmental properties, such as organic and inorganic matter type and concentration, as well as ionic strength and the presence of mono- or divalent ions. The fate descriptors were detailed for the following compartments: wastewater treatment plant (WWTP), water, soil and subsurface, and for the following transformations: heteroaggregation, sedimentation and sulfidation. The time-dependency of chemical species concentrations is an essential feature of this model, because it serves to link exposure scenarios with hazards that change over time.
The main achievements attained are described below for each environmental compartment addressed during the project.
--Main achievements related to WWTP –
1. A model was developed to predict partitioning of metals amongst sludge and effluent. Parameters are residence time, total suspended solids, and the NM/sludge partitioning coefficient at steady state (Kd).
2. A database was constructed from literature values suggesting that Kd can be related to NM size and the Hamaker constant.
3. WWTP microcosms were run using Ag NM, confirming the size dependence and lack of aggregation in WWTP. Neoformation of small AgNP that remain suspended was also found.
4. Kinetic batch attachment tests and sedimentation tests using WWTP confirmed the size dependence and effect of TSS. Lack of effects of coating, shear forces or ionic strength was found.
5. The final model predicts the mass and speciation of NM that ends up in soils AND freshwater as a function of size and Hamaker constants.
6. This knowledge is applicable in a safer-by-design context, e.g. to avoid emission of NMs to freshwaters.
--Main achievements related to the aquatic compartment—
1. Dissolution, heteroaggregation and sedimentation experiments were performed to address the main data gaps identified regarding fate of nanomaterials in the aquatic compartment. Several CuO, ZnO and Ag NMs with different manufactured coatings and sizes, and different water types (different composition and types of organic and inorganic matter) showed that the dissolution of the NMs is not significant and independent of the water composition, the manufactured coating of the NM and the size of the NM.
2. Heteroaggregation and sedimentation experiments confirmed that these processes depend on the presence of organic matter, but not on the water composition, manufactured coating, or size of the NM.
3. Several databases were constructed from literature values and experimental data obtained within the project containing physicochemical parameters of numerous freshwaters that can be found in Europe, properties of natural organic and inorganic colloids, and properties of NMs and respective transformations rates in water.
4. Statistical analysis of these databases confirmed the experimental results of the tests conducted within the project: organic matter properties do affect heteroaggregation and sedimentation, but the other properties investigated, ie., manufactured coating, size and chemical composition, do not.
5. A model was developed to predict the speciation of the NMs in the aquatic system. This model includes heteroaggregation, sedimentation, and transport along the river. The critical parameters of this model are natural organic and inorganic matter properties, and attachment efficiency. The final model predicts the speciation of the NMs discretized in size bins in the aquatic system as a function of the attachment efficiencies between the NMs and the natural organic matter.
--Main achievements related to the soil compartment—
1. A model was built where the pore-water and solid concentration of NMs in soils can be predicted based on easily measurable soil parameters such as texture, packing density, rainfall intensity, and attachment, detachment rates of NMs.
2. The model was refined further to relate attachment rates to the attachment efficiency for a specific NM – soil combination.
3. A database of 503 attachment efficiencies was built, but first statistical analysis did not reveal a straightforward relation between soil/NM properties and the attachment efficiency.
4. Experiments did show a poor mobility of larger NM compared to smaller NM of the same type, in the same soil.
--Main achievements related to the subsurface (or groundwater) compartment—
1. The model of NM reactive transport in groundwater was developed together with a database containing the model parameters. The performance of the model was evaluated using the GUIDEnano case-study, nZVI field application for groundwater remediation.
WP6: HAZARD ASSESSMENT
The main work of this WP was developing a strategy for predicting the ecotoxicological and human health hazard of the exposure-relevant NM forms released into exposure situations throughout the lifecycle of NM-enabled products.
--Development of a hazard assessment strategy—
The eco- and human toxicologists worked together to develop a hazard assessment strategy to estimate safety limit values making the fullest use of existing information while allowing prediction of hazard on the basis of different levels of data availability (each with an associated level of uncertainty reflecting the richness and quality of data available). The final hazard assessment strategy developed in GUIDEnano is presented in Figure 6. Existing OEL, DNEL or PNEC values for the material under evaluation will be used, if these are available. Otherwise, generic highly conservative thresholds can be used. When necessary, these can be refined based on available toxicity studies. The strategy mostly relies on information from studies following harmonized testing guidelines such as OECD and/or ISO, but is designed to also make use of ‘other non-standard’ studies and toxicity information. When assessing already existing individual toxicity studies from literature the hazard assessment strategy involves the establishment of scores to inform on quality (i.e. how good and reliable a study and its reporting is), relevance (i.e. how relevant the NM study is for the respective environmental compartment or human pathway/endpoint) and similarity (i.e. how well does the NM exposure in the study to be used reflect the exposure relevant form of nanomaterial which is being assessed). These scores are used to select studies that can be included in the process to derive safety limit values. In addition, the similarity score is used to introduce a ‘dissimilarity’ uncertainty factor.
--Evaluation of the role of nanomaterial coating on toxicity--
Hypotheses-driven experiments (different cores and coatings) were performed to evaluate the assumptions identified as most critical to reduce the most prominent uncertainties (e.g. from read across) in the hazard assessment process. To test the influence of the core material and the different coatings a base set of three different core materials (TiO2, CeO and Ag) each with three different coatings (citrate, PEG and an hydrophobic coating: DDPA in the case of TiO2, CeO and an oleylamine in the case of Ag) was selected for testing in a wide range of in vivo and in vitro test systems. No consistent trends were observed for the effects of coatings. These effects depended on the core material and the experimental test.
--Hazard characterization of the materials of the GUIDEnano case studies—
The nanomaterials of several of the project case studies were evaluated to allow the refinement of the hazard assessment when these case studies were evaluated by the industrial partners using the GUIDEnano Tool. The results of these studies are summarized below:
1. Antifouling paints (HEMPEL): Single species tests with selected representative standard bacterial (Pseudomonas putida), algal (Raphidocelis subcapitata) and daphnia (Daphnia magna) species were performed with the single components of the paints (micro CuO, Cu pirythione and ZnO; or nano ZnO). In addition, efficacy testing of the painted panels (with all the different paint types) was performed under controlled laboratory conditions as well as natural conditions in the river Thames. In addition, the bacterium Psedudomonas putida was exposed to release waters from the paint panels and none of these waters caused toxicity. Similarly, Daphnia were exposed to the releases from the paint panels in Daphnia culture medium. The reduction of ZnO particle size (micro to nano) helped to mitigate the release of Cu to the Daphnia magna medium and did not enhance the toxicity of the Globic paint to this specie.
ZnO NPs were also doped with Mn or Co (performed by DEI). These doped NPs did not increase the in vitro toxicity in fish cell lines.
2. Ceramics (TORRECID): TiO2 NPs from TORRECID had low toxicity in fish cell lines and Daphnia magna. In addition, the toxicity of the liquid dispersions and their respective dispersants to three bacterial species was tested under illumination and in the dark. Toxicity increased under light conditions. Clear conclusions on the toxicity of the NM are challenged by the fact that dispersants alone already caused some bacterial toxicity.
3. House-hold cleaning agent (NSER): In vitro, silver doped and undoped TiO2 NPs they did not induce cytotoxicity, immunotoxicity, genotoxicity nor toxicity in THP-1 lung macrophages and 16HBE lung epithelial cells and on the intestinal membrane model, although an increase of ROS production was observed in the latter model. In rodent intratracheal aspiration studies, they also showed very low toxicity, however, both NPs persisted in the mouse lungs up to one month after exposure, and inflammation and systemic genotoxicity were observed in the case of undoped NPs.
4. Photocatalytic hot bituminous mixture (Servià Cantó): Cytotoxicity and immunotoxicity were induced in vitro by the mixture (resin + TiO2 NP) in differentiated macrophages at the highest concentration tested. In contrast, exposure to the mixture or the individual components caused no genotoxicity in vitro and in vivo, no toxicity in the intestinal membrane model, and no in vivo immunotoxic effects. However, TiO2 NPs alone persisted longer in the mouse lungs than when they were exposed in combination with the resins.
5. Nanocelluloses (INNVENTIA): No cytotoxic effects were associated with the in vitro exposure to unmodified or surface-modified NFCs, whereas the observed inflammatory response to NFC might be driven by the material surface chemistry.
--Evaluation of efficacy of safer-by-design approaches in terms of hazard—
A number of experimental studies were performed in support of WP8’s safer-by-design (SbD) approaches (see Table 1).
From the human hazard point of view, the model Ag NPs showed no clear size dependent toxicity nor differences in Ag ion release in cell culture medium after 24 h. The application of PVP-coating and the oxide passivation layer (AgO) did not succeed in reducing the toxicity of the pristine NPs.
In the ecotoxicity studies, with different aquatic and terrestrial species, an increase in Ag NP size reduced toxicity and bioaccumulation, sulfidation of metallic AgNPs to Ag2S also decreased toxicity. On the other hand, no consistent results among different experimental species and test set-ups were obtained for AgO and Ag-PVP NPs. The Ag microcapsules provided by INOTEX were consistently more toxic to the different bacteria strains than the MSA- and TA-modified Ag NPs.
--Evaluation of toxicologically-relevant interactions of NM with other coexisting substances—
The purpose of this task was to evaluate how co-exposures with other hazardous components present in the NM-enabled product matrix or environmental pollutants could result in changes in toxicity of the NM or coexisting substances. The following type of scenarios were addressed:
1) Organic compounds of toxicological concern that are present in the nano-enabled product matrix. We tested the effects of three NMs from the case-studies containing other coexisting substances: antifouling paints (Hempel), house-hold cleaning agent (NSER), photocatalytic hot bituminous mixture (Servià Cantó). See description of the results in the section ‘Hazard characterization of the materials of the GUIDEnano case studies’.
2) Ubiquitous pollutants that can coexist in aquatic media such as endocrine disruptors and dioxin-like compounds, in combination with Ag, CeO2 and TiO2 nanoparticles. Some interactions were identified, which in part were possibly due to the adsorption of model organic pollutants on the nanoparticles surface.
3) Combination of different nanomaterials at low (non-toxic) concentrations. In vitro cytotoxicity assays with a hepatoma fish cell line co-exposed to different concentrations (from non-toxic to toxic) of Cu NPs and a non-toxic concentration of ZnO NPs were performed. Results in vitro indicated that the presence of non-toxic concentrations of ZnO NPs produced an increase in the toxicity of the Cu NPs and that this effect was produced by the NP and not by the Zn ions released. The co-exposure of Cu and ZnO NPs both at non-toxic concentrations also produced an acute toxic effect to fish.
WP7: RISK ASSESSMENT
The main goal of this work package was to develop a strategy for risk assessment of release- and exposure-relevant NMs in NM-enabled products throughout the various product life-cycle stages. This risk assessment strategy was incorporated in the interactive web-based GUIDEnano tool and was evaluated with hypothetical and real case studies within the project.
The initial decision flow for risk assessment incorporated in the GUIDEnano tool is presented in Figure 6. The safety limit value is comparable to the Derived No Effect Level (DNEL) for human health and Predicted No Effect Concentration (PNEC) for environment according to the REACH regulation.
Summary of the steps to derive a safety limit value:
1. Select hazard studies with associated effect levels (NOAEL, LOAEL, BMD, etc)
2. Determine modification/assessment factor for each effect level
3. Derive safety limit value by applying the assessment factors for each effect level (including a factor for dissimilarity)
4. Derive overall safety limit value per endpoint
5. Risk assessment: compare safety limit value with corresponding exposure level
The required factors (step 2) were listed and for each factor the purpose for application and the value are included. The risk assessment in GUIDEnano Tool v3 is deterministic, but some information is provided to the user to inform on the sources of uncertainty for the hazard limits derivation. For each assessment factor, it is indicated if it represents modification, uncertainty or variability. This information is needed to determine the possibility for reduction of the uncertainty of the safety limit value.
An output report has been designed and generated by WP7 together with the tool builders. This output report consists of a detailed background report with all information generated by the Tool based on the input of the user. This will be provided to the user after using the Tool, together with an executive summary of the risk assessment result (probability of risk) and proposed follow up actions (reduction of uncertainty, mitigation of risk by for instance safe by design strategies).
Case studies reported in the literature or hypothetical were used to evaluate the version 2 of the Tool. Feedback from this evaluation and feedback from stakeholders (e.g. industry, (re)insurance communities) obtained in dissemination events and via tailored questionnaires was used in the updates towards version 3. WP7 also monitored to what extent the industrial partners of the project were able to correctly use the GUIDEnano Tool during the evaluation of the project case studies. The specific questions that were addressed during these evaluations were the following: are the correct data used? Are the data inserted into the correct parameter fields of the tool? Are the relevant modules used for evaluation of the NM and NM-enabled product? Are the correct exposure tools and hazard studies used for the evaluation? Is the tool used as anticipated? This evaluation identified some issues, but the conclusion is that they can be solved by the availability of a manual and a more user-friendly version.
The GUIDEnano Tool was also evaluated in comparison to other existing tools (control banding tools: Stoffenmanager, Nanosafer, Nanotool, ANSES; Risk prioritization tools: Swiss Precautionary Matrix, NanoRiskCat, decision support tool; Weight-of-evidence approaches; Other: Licara NanoScan and ECETOC-TRA; MARINA framework, IATA, SCENIHR, CPM model, Probabilistic models: Simplebox4Nano), and the main advantages identified are the following (more details can be found in D7.5):
1. It is a complete tool, combining both hazard and exposure assessment and covering risks for workers, consumers and environment.
2. The tool is not limited to specific activities or exposure scenario’s and is flexible according to the users interests and focus.
3. The tool can cover the whole life cycle of a NM, from synthesis of the NM to the end-of-life phase including recycling. The GUIDEnano tool takes into account the changes in properties of the NM throughout the life cycle.
4. The tool integrates risk assessment and risk management, and specifies uncertainties.
5. The tool results in a quantitative risk assessment.
6. The tool is not for screening of risks or prioritization, but it supports decision-making. Decision-making can be performed for each scenario separately, without the need for comparison to other scenarios.
7. The tool matches with existing regulatory accepted risk assessment methods. For example: the hazard strategy and read across/ similarity procedures are strongly inspired by REACH.
WP8: RISK MANAGEMENT
Work package 8 aimed to propose, develop and validate risks mitigation measures (RMM) to reduce the potential risks identified through the risk assessment provided by the web-based Guidance Tool GUIDEnano. In such a way the final user, can select the most appropriate RMM allowing to control the risks highlighted and decrease them to an acceptable level, making the whole process safer. Among possible RMM, safer-by-design (SbD), occupational exposure control and advanced waste management strategies, were evaluated within the context of GUIDEnano case studies.
--Main achievements related to safer-by-design strategies--
Safer-by-design strategies were proposed taking into account the case studies and the NM employed and focusing on relevant endpoints and effects/risks to mitigate. SbD strategies were intended to:
1. Re-design relevant physicochemical properties of NM to mitigate their hazardous potential, while maintaining their characteristic functionality within the NM enabled product,
2. Avoid or reduce the release of NM during different life cycle stages of the nano-enabled products by improving compatibility between NM and matrix, to lower the possibility of environmental and/or human exposure to NM,
3. Avoid or reduce the environmental and/or human exposure to NM by designing and synthesizing less reactive and/or less persistent NM.
A set of SbD NM were synthesized at lab-scale level with targeted modifications of relevant physico-chemical properties and were provided to the different WPs to be evaluated for specific endpoints/ functionalities. For selected case studies, the resulting SbD NMs were implemented, namely in the case studies for TORR, LATI and INOTEX:
1. TORR modified the composition of TiO2 photocatalytic coating by developing a SbD approach aimed to lower the eventual NM release. Novel coating made up of TiO2 NMs and frit NMs were developed. The possible reduction of the NM release was tested through ageing/release experiment (WP3).
2. LATI implemented SbD NM by the substitution of TiO2 NM with SiO2 coated TiO2 NM as nanofiller, to suppress the photodegradation of polymeric nanocomposites and to improve their mechanical properties. The efficacy of this strategy was evaluated by WP3.
3. For the textile case study, different SbD Ag NMs were synthesized by Plasmachem (Ag coated with tannic acid, Ag coated with mercaptosuccinic acid) and VHIR (Ag nanowires with two different sizes) and delivered to INOTEX to functionalize textile samples providing them antibacterial properties. The SbD strategies were focused on a better compatibilization of NM within the matrix in order to avoid NM release to the human and environmental compartment during the use phase of the nanoenabled product. WP3 evaluated the efficacy of this strategy by means of “Washing” release experiments.
--Main achievements related to occupational exposure control measures—
One of the main achievements was the evaluation of the effectiveness of the personal protective equipment (PPEs) commonly employed by the industrial partners involved in GUIDEnano, with the objective to obtain for each of them a nominal protection factor (NPF) against NMs. The NPF of different PPEs have been determined, modified and validated using standard protocols available for bulk materials. Depending on the nature of the NM tested, two test protocols were adopted:
• a static test protocol to evaluate the NPF of PPEs against metal oxide NMs, which are considered potentially hazardous materials. These tests were performed under simulated conditions and using mannequins in substitution to individuals,
• a dynamic tests protocol to evaluate the NPF of PPEs against NaCl nanoparticles. NaCl is worldwide recognized as the conservative ‘Not hazardous’ test agent. PPEs were worn by different individual, thus conducting the ‘Practical Performance tests’ under the more realistic dynamic conditions.
Several types of masks, suits and gloves were investigated under simulated conditions performing static tests using different NM and at different concentrations (including also NM of different sizes). Results demonstrated that suits and masks, especially respiratory filters, offered a quite good NPF, sometimes slightly lower than the default value. Data collected showed unlike performance of the glove depending on NM type and concentration employed, therefore further tests need to be performed.
Full and half masks were tested under the dynamic test protocol. The credited NPF varied from 15 to 3000 (mostly due to their different fit to the facial geometry, being one of the mayor factors affecting the protection factor, more details in D8.2). Other alternative solution for respiratory protection (such as ventilated single use hoods) reached NPF of 65 000.
Regarding whole body protection, the PF for Protective suits varied from 1 (zero protection) for the overall non-woven up to 120,000 for the ventilated protective suit.
These investigations show that available PPEs can offer a wide range of protection levels and that the choice of the PPEs to be used depend on the Risk analysis and toxicity of the nanoparticle considered.
--Main achievements related to waste management strategies--
The work performed on the waste management strategies was aimed to reduce the NM environmental exposure (and exposure through the environment) by application of novel and known waste management strategies and by proposing waste reduction and potential implementation of recycling processes.
The seven GUIDEnano production processes/case studies were described in collaboration with the corresponding industrial partners (Hempel, Innventia, Inotex, Lati, Torrecid, Plasmachem and Servià Cantó). Then, for each case study, a production process diagram including a list of the nanowaste fractions generated, were depicted. Being the water containing NM one of the main waste fraction generated, different waste water treatments were selected according to their relevance for industry and their NM removal efficiency, these included settling, electrocoagulation, membrane distillation and advanced oxidation processes.
The efficiencies of the different strategies for NM removal were evaluated together with industrial partners and were collected in a compilation table, where information on “waste fractions”, “waste attributes” and “treatment process” was included. This information was incorporated into the GUIDEnano Tool.
--Incorporation of experimental and theoretical data on RMM into the GUIDEnano Tool--
Nano specific data collected from published literature and other EU funded projects, as well as data from the experimental evaluation performed by ITENE and HWELL on the effectiveness of PPEs was incorporated into the GUIDEnano Tool by:
1. The provision of protection or effectiveness factors for exposure engineering controls. The ECEL database was adapted to include nano-specific information and to allow its incorporation into the GUIDEnano Tool.
2. The provision of effectiveness factors for PPEs.
3. The provision of removal efficiency for different waste treatments.
WP9: TOOL DEVELOPMENT
The main objective of this WP was to develop the web-based tool. The design of the tool: Structure, flow, connections of all the components of the risk assessment (exposure, fate and hazard) and risk management strategies, is the result of a team work of all the technical WP experts in the different scientific areas (WP3-WP8) and the software specialists.
Three versions of the GUIDEnano Tool were delivered during the project.
1. GUIDEnano Tool v1 was released to consortium in the 18th month meeting (May 2015). In v1 the focus was on implementing the main structure of the tool in an object-oriented manner. First, class-diagrams where developed together with the experts for each individual wp. Next, these wp class-diagrams where merged into one single GUIDEnano class diagram, identifying overlap and harmonizing nomenclature. Relevant class-attributes (properties) where identified and assigned to the defined classes. In parallel, v1 of the application framework was developed, allowing online usage of the tool under development. Finally, v1 allowed the user to describe the relevant nanomaterial forms and identify the potential hazard hotspots during the life cycle of a nanomaterial/ nano-enabled product due to related activities and potential release(s).
2. GUIDEnano Tool v2 was released to consortium at the end of April 2016. In v2 the focus was on the implementation of the ‘behavior’ of the identified classes, like: rules, decision trees, algorithms. Over a hundred toxicity study classes covering both human and eco hazard were incorporated. The knowledge implemented in v2 allowed users not just to identify but also to quantify the risk of certain prioritized hotspots. This version was the basis for the internal evaluations (see WP7 and WP10).
3. GUIDEnano Tool v3 (Figure 8) was released at the Final consortium meeting. First, the feedback and related issues as a result of the evaluation were taken into account. Special focus in v3 was the improvement of the kinetic fate module, allowing now to predict the fate of nanoparticles per size-bin. Also, a first implementation of nanomaterial similarity for the inhalation hazard endpoint was built in.
The tool has been built on a modular basis which will be easy to update in the future.
WP10: VALIDATION OF THE GUIDENANO TOOL IN REAL CASE STUDIES
Industrial partners used the GUIDEnano Tool version 2 to evaluate the risks for their case study. During this process, when needed, they received support from the experts in each part (WPs 3 to 9).
The high potential of the Tool was well recognized during this evaluation, although the current version was not considered to be sufficiently user-friendly. Another main limitation that some industrial partners faced during the assessment process was the reluctance of their suppliers to provide characterisation data for the NMs. However, the main message to highlight about GUIDEnano Tool is that it contains all the complexity and components needed for assessing human and environmental risks of nanomaterials and nano-enabled products in all their life cycle stages. Furthermore, it is able to propose risk mitigation measures in case of identification of risks. Making something complex into a user-friendly version is the least problem that we face.
Potential Impact:
The Commission communications towards a European strategy for nanotechnology listed actions to support a high level of public health, safety, environmental and consumer protection including: (i) to identify and address safety concerns (real or perceived) at the earliest possible stage, (ii) to reinforce support for the integration of health, environmental, risk and other related aspects into R&D activities together with specific studies, (iii) to support the generation of data on toxicology and ecotoxicology (including dose-response data) and evaluate potential human and environmental exposure, (iv) to promote the adjustment, if necessary, of risk assessment procedures to take into account the particular issues associated with nanotechnology applications, (v) and to promote the integration of assessment of risk to human health, the environment, consumers and workers at all stages of the life cycle of the technology.
GUIDEnano was designed to guide the users (Industry, consultants, R&D staff, society) to assess the risks of any nano-enabled products at any of their life cycle stages. The ultimate goal of the GUIDEnano Tool is to assist both industry and society to ensure the safety of nano-enabled products considering all the potential release materials along the product life cycle, and their ultimate fate. Furthermore, the release assessment contributed to the industrial development of safer products by tailoring ENM properties and modifying matrix – NM interactions in order to reduce exposure.
GUIDEnano is a complete tool, which combines both hazard assessment and exposure assessment and covers risks for workers, consumers and environment. It takes into account different exposure routes and durations, and different endpoints of toxicity. The characteristics of NMs and corresponding potential risks can vary dependent on the life cycle stage, exposure route and the system it is in (human, environmental), which are all taken into account in the GUIDEnano tool.
Activities (exposure scenarios) can be created in the tool. This means that the tool is not limited to specific activities or exposure scenarios and is flexible according to the users interests and focus.
The tool involves the whole life cycle of a NM, from synthesis of the NM to the end-of-life phase including recycling. Most data available are based on pristine NMs, however, at later stages of the life cycle human or the environment can be expose to processed (e.g. coated) or aged NMs (recycling). The GUIDEnano Tool takes these changes in properties of the NM throughout the life cycle into account.
The Tool integrates risk assessment and risk management, and specifies uncertainties. Based on the integration of all these aspects, the uncertainties can be diminished and risk mitigation strategies (safe by design, exposure control measures, waste management) are recommended in the Tool, in an iterative process.
The project has played an active and important role in the refinement of the human and environmental hazard strategy for risk assessment, which includes a similarity algorithm for read across purposes. In addition, the gained expertise on developing/ modifying hazard and exposure models for risk assessment of nanomaterials will be further developed in running and future projects (e.g. the H2020 NANOFASE, calibrate, GRACIOUS).
The Tool results in a quantitative risk assessment, allowing a justified assessment for each scenario. Based on hazard assessment, and taking into account similarity and quality of data, a Safety Limit Value is derived and compared to exposure concentrations, resulting in a ratio relating to a probability of risk. Together with the uncertainty relating to this risk value, it provides a founded view of the probability of risk and which actions may be taken to reduce the risk, if necessary.
The Tool is not for screening of risks or prioritization, but it supports decision-making. Decision-making can be performed for each scenario separately, without the need for comparison to other scenarios.
The Tool matches with existing regulatory accepted risk assessment methods. For example: the hazard strategy and read across/ similarity procedures are strongly inspired by REACH. Also accepted hazard testing methods in the tool match with OECD approved methods
GUIDEnano tool will advise companies to invest in the research which contributes most to reduce the potential risks by applying risk mitigation measures or reducing uncertainties. GUIDEnano output report gives the user of the Tool an extended overview of the potential risk (including uncertainties) of their NM-enabled product. It also gives options to either reduce the risk and/ or the uncertainties.
Economic Impact
Economically, the impact the GUIDEnano Tool will have on the nano-enabled materials industry will be significant as more of the industrial stakeholders need to assess the risks associated with the production of such materials.
The time to market for new nano-enabled products and materials will shorten because industry is guided in a uniform, reproducible and testable way through all relevant steps of the risk assessment. The Risk Assessment framework in GUIDEnano is generic and therefore can also be applied for other substances related (future) risk assessment tools even outside the nano-knowledge domain.
The impact of the tool might be further increased by introducing specials, like an occupational version, consumer version or environmental version all using the same knowledgebase but with custom made user interfaces to enhance usability. This will increase the potential market for licensing the tool and allows differentiation in pricing.
The practical feedback from industrial partners is a significant contribution to the tool development in terms of user-friendliness and practical needs of different industrial sectors. The feedback of industrial partners is of paramount importance to increase the market success of the tool and academic partners have already worked with relevant WPs to increase user-friendliness and to avoid some bottlenecks in the wide adoption like confidentiality issues.
Impact on Regulations
GUIDEnano will help implement the EC communication Regulatory Aspect of Nanomaterials (COM (2008)36629 and COM (2012)57230) which calls for improvement in the knowledge of characterization, hazards, exposure, risk assessment and risk management of NM. The Tool matches with existing regulatory accepted risk assessment methods. For example: the hazard strategy and read across/ similarity procedures are strongly inspired by REACH. Also accepted hazard testing methods in the Tool match with OECD approved methods. This will help in easy implementation and future exploitation as a trusted tool for risk assessment of nanomaterial and nano-enabled products.
To maximize the impact of GUIDEnano, the consortium has been active in attending events and workshops to establish cooperation (aligning with their discussions and decisions) with international organization, such as OECD and ECHA, including the following:
OECD Working Party on Manufactured Nanomaterials, Expert Meeting on Categorization of Manufactured Nanomaterials (17-19 September 2014 Washington (USA)) Stimulus presentations: "Nanomaterial classification considerations for environmental fate" the GUIDEnano WP6 lead was asked by DG-Env to represent the EU delegation and, with Dr Iseult Lynch from NanoMILE, asked to present one of the Stimulus presentations in session 4 on Environmental fate implications on Categorisation and Risk Assessment. They presented not only the GUIDEnano and NanoMILE aspects, but summarised the relevant elements of all the NSC WG3 projects. Additionally D.Brouwer (TNO) and JM Navas (INIA) were invited to this expert meeting as respectively the Dutch and Spanish representative at the OECD Working Party on Manufactured Nanomaterials.
For ECHA’s Topical Scientific Workshop – Regulatory Challenges in Risk Assessment of Nanomaterials (23-24 October 2014, Helsinki, Finland) GUIDEnano representatives were invited onto the Scientific Steering committee for developing the event, present in the plenary sessions and sit on the panel in the discussion sessions. These brought together close to 200 experts in the field of risk assessment of nanomaterials representing academia, policy makers, industry and NGOs, to discuss how to address current challenges from the regulatory perspective which can be reflected and employed in the ongoing and future research topics on nanomaterials. The discussions were reinforced by information on recent developments and on risk assessment methodologies (including GUIDEnano’s) applied in chemicals management both within and outside the European Union.
Impact on Standardization
GUIDEnano utilised the nanoSTAIR approach which is a process and a platform to support standardization for nanotechnologies. GUIDEnano deliverables were all systematically checked by a standardization expert against a number of committees including (ISO/TC 24/SC 4, ISO/TC 201, ISO/TC 202, ISO/TC 209, ISO/TC 229/JWG 1, ISO/TC 229/JWG 2, ISO/TC 229/WG 3, ISO/TC 229/WG 4). No content or results of GUIDEnano were good candidates for further standardization process. In particular, GUIDEnano activities were mainly divided in two directions: Development of algorithms/ roles/ tables/ decision trees/ strategies to build up the RA tool and generating data to cover data gaps in different areas by using as far as possible standardized or well-established protocols and methods. Working together with the partner in charge with the task of standardization in GUIDEnano (DIN- German Institute for standardization) facilitated the identification of new protocols or new methodologies as potential candidates for going through a standardization process. Furthermore, the use of nanoSTAIR approach during the project was an opportunity for all the partners to get familiarized with it to apply it in their future work.
GUIDEnano was also very active in Nanosafety Cluster standardiazation subgroup. This led to the preparation of documents on standards and standardization in all projects related to nanotechnologies. Including reports containing a compendium of relevant committees, their standards and their current activities. These documents can be found published in the nanosafety cluster website (http://www.nanosafetycluster.eu/working-groups/7-dissemination-wg/standardization/how-to-bring-your-nanosafety-research-to-standards-a-comprehensive-set-of-guidance.html).
Dissemination and Exploitation
The project engaged various stakeholders to whom the results of the project were communicated to. The consortium was dedicated to to attend conferences, publish papers in peer reviewed journals, share news and updates of the project on a regular basis, during the lifetime of the project. While results were widely shared by several partners from the consortium at all the main conferences around the year, the main result of the project, GUIDEnano Tool, was not publically shown until the second year of the project. General information about GUIDEnano was initially disseminated by means of printed and digital media. In month 3 of the project the website was established with domain name (www.guidenano.eu) with general information about the project. Updates about the project, events, news, electronic format of printed media were all included on the website when ever available. In month 6 the project leaflet was produced. Printed versions were distributed at conferences, meetings and events whenever possible. An electronic version was also made available on the project website. An updated project leaflet was produced in month 30 with printed and an electronic version. Two newsletters were published during the project time. Both were made available on the project website and were distributed to stakeholders through the Nanosafety Cluster distribution channels.
Project videos were produced. The first one was a general video about the project and how the Tool helps the industries and nano-enabled products manufacturers to evaluate the associated risks. This video was released in anticipation of the Tool and to disseminate that it is functional and would be ready soon. The second video was more professionally made for wider distribution. Social media was also use to disseminate and communicate the project results. A twitter account was created and the consortium was given access to allow publication of news, events and updates about the project. The twitter feed is available on the project website. LinkedIn was also used as a platform for communication. The consortium was very active in disseminating the project results consistently.
More than a 100 oral presentation and posters were presented at European and international conferences covering all technical work packages. Five articles were published peer review journals with one currently under revision. In the pipeline, there are currently 2 articles submitted and several papers in the draft form for the different WPs. One patent was filed by CEA for methods of tagging and labelling nanocellulose for monitoring the release of the nanomaterials from products. Specific dissemination targeting stakeholders and regulators was also done to maximize the project impact and exposure.
Concerning the scientific publications in peer-review Journals: The main publishable outcomes came late during the project (as expected, looking at the DoW); therefore, publications are currently under preparation. The first year of the project was dedicated to build-up the structure of the Tool and the experimental work did not start until the second year. And the duration of some experiments also caused some delays in the generation of experimental data. Therefore, partners from the different WPs are currently working on writing the publications on their specific area. Furthermore, the revised and modified decision trees, algorithms, models, strategies will be soon published (e. g. Quality assessment Tool- submitted, similarity approach of GUIDEnano-ready for submission).
Showcasing the GUIDEnano Tool was crucial for its communication and pre-marketing but also for its development. Thanks to these public presentations, the Tool had various feedback sessions very useful for its further development but also greatly contributed to its diffusion among the targeted stakeholders and beyond.
The activities done to present the Tool to stakeholders can be summed up in two main types: general presentations and in-depth presentations. The former ones were often shorter and did not go into the technical details and functioning of the Tool. The aim was to present its most important features and its added-value for scientists and industries. These presentations were rather short and the public was less specialised around the risk assessment of nano-enabled products.
• Nanomaterial Safety Assessment Conference in Malaga
From the 7th to the 9th of February 2017, five large FP7 research projects (NANOSOLUTIONS, SUN, NanoMILE, GUIDEnano and eNanoMapper) jointly organized a conference in Malaga (Spain), that aimed at presenting the main results achieved in the course of the projects fostering a discussion about their impact in the nanosafety field and possibilities for future research programmes. The conference gathered consortium partners from the organizing projects, as well as representatives from other EU projects, industry, government, civil society and media.
• Joint Scientific Conference of ProSafe & OECD
From the 29th of November to the 1st of December 2016, a joint scientific conference of ProSafe & OECD took place at the OECD Conference Centre in Paris. During 3 days, researchers coordinating large European projects in the field of nanosafety and regulatory authorities such as the European Commission and the OECD met and presented their work done and their vision in the field.
• Nanomaterials: Industrial workshop on safe-by-design (Bilbao, 24-25 April, 2017)
• Towards safe-by-design (EuronanoForum, June 23rd, Malta, 2017)
More in-depth workshops/ seminars including step-by-step explanation of the Tool:
• Stakeholder workshop during NANOSAFE 2016
From the 7th to the 10th of November 2016, the fifth International conference nanoSAFE took place in Grenoble hosted by the CEA in the MINATEC. GUIDEnano had a strong presence to present its online Tool for risk assessment of nano-enabled products and organised on the 10th in the morning a stakeholder workshop inviting industrial and scientific partners to a presentation showcasing for the first time the interactive Tool.
• GUIDEnano Webinar: On the 8th of March 2017, LEITAT organised a webinar directed to insurance companies. With the support of Pinsent Mason, partner of the project, around 5 professionals from the insurance sector attended the webinar. During an extensive presentation about the rationale, features, modules and case studies, Gemma Janer from LEITAT presented the results of almost 4 years of research and development. The core of the presentation was articulated the modules of the Tool, being materials, activities, compartments, exposure, hazard and risk assessment and management. By showing the Tool itself, the insurance companies could see the current stage of development which was already fully functioning at that time.
The presentation was followed by a discussion with the audience guided by questions prepared by GUIDEnano team. It included the most interesting features for the audience and possible extensions currently missing that would be useful for the audience.
• Webinar for caLIBRAte risk assessment partners.
Exploitation
Exploitation of GUIDEnano results was a priority from the start of the project. In the first 6 months the consortium identified 20 potential exploitable results related to a number of partners. Most of these potential exploitable results were then considered results that are/ will be published or patented. However, the overall consensus was that the Tool was the main outcome with the most potential for successful exploitation. GUIDEnano Tool has many advantages over existing or otherwise developed risk assessment tools. These advantages include:
• Software more complete than the current competitors on the market.
• Generating valuable information for users.
• Software flexibility that allows easy implementation of new updates in any of the modules.
• Cost savings to the customer, when offered through SaaS, since users do not have to incur the cost of purchasing the software and installation, but only pay for accessing the service.
• As the tool is housed in a central server, all the data inserted from the different users will be used as feedback for the tool, contributing in the improvement on predictability of the different modules of GUIDEnano.
There are a number of options to exploit the Tool. This may be done through a basic license, premium license, license through “pay per use” or a free limited license. A preliminary study of the costs associated with updating the Tool to bring it closer to market ready status was conducted. At the current state the Tool is complex to use without training, therefore necessary steps needs to be taken to simplify its use for customers in order to gain market potential. Future exploitation of the tool also may include specific package software tailored for specific industries/ users/ communities e.g. textile, paints, etc. the tool may also be updated through the participation in new projects which will generate new knowledge that can be integrated into the tool to make it more complete.
After a first revision of the exploitation plan presented at the end of the project, LEITAT and THINKWORKS (TW) generated a more detailed plan to exploit the Tool. First of all, the IPR issues needed to be solved with an official written document and then the immediate steps needed to generate new versions of GUIDEnano Tool that we can commercialize in the near future. The first task is to work on getting GUIDEnano Tool v3 as a free accessible version simplifying what is needed to make it as user-friendly as possible. In the short –medium term the participation of LEITAT and, in some cases, also THINKWORKS in running or nearly starting projects (NANOFASE, caLIBRAte, GRACIOUS, NANOCOMMONS) will allow us to further implement and improve different modules of the Tool. And then, further developments will lead to more advanced versions of the Tool which can then be sale through licenses. Trainings and consultancy services are foreseen within the exploitation plan discussed for GUIDEnano Tool. Dissemination activities will continue in order to promote the Tool and get engagements with all the organizations/ communities/ researches. The first step is the use of the important dissemination platform of ECHA: The observatory for nanomaterials.
Furthermore, the work on safe-by-design that was initiated in GUIDEnano with some industrial partners will be continued in other projects to be able to consider patenting some of the results (NANOFASE, caLIBRAte).
List of Websites:
www.guidenano.eu
Project Coordinator: Socorro Vázquez (svazquez@leitat.org)
LEITAT Technological Center
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