Abstract Driven by the concept of the 'four generations of nanomaterials', the current state of the knowledge on risk assessment of future generation is explored for active nanomaterials. Through case studies, we identify challenges and evaluate the preparedness of characterization methods, available risk assessment modeling tools, and analytical instrumentation for such future generation active nanomaterials with dynamic hybrid structures of biotic–abiotic and organic–inorganic combinations. Currently available risk assessment tools and analytical instrumentation were found to be lacking the risk preparedness and characterization readiness for active nanomaterials, respectively. Potential future developments in risk assessment modeling tools and analytical techniques can be based upon this work which shall ensure long-term safety of the next generation of nanomaterials.
Abstract Dustiness is not an intrinsic physically defined property of a powder, but the tendency of particles to become airborne in response to mechanical and/or aerodynamic stimuli. The present study considers a set of 10 physical properties to which the powder dustiness can be attributed. Through a preliminary investigation of a standardized continuous drop test scenario, we present first set of results on the varying degrees or weights of influence of these properties on the aerosolization tendency of powder particles. The inter-particle distance is found to be the most dominant property controlling the particle aerosolization, followed by the ability of powder particles to get electrostatically charged. We observe the kinetics involved during powder aerosolization to be governed by two ratios: drag force/cohesive force and drag force/gravitational force. The converging tendencies in these initial results indicate that these physical properties can be used to model dustiness of falling powder, which can eventually be used in risk assessment tools for an efficient exposure estimation of the powders.
Abstract Measured data are generally preferred to modelled estimates of exposure. Grouping and read-across is already widely used and accepted approach in toxicology, but an appropriate approach and guidance on how to use existing exposure measurement data on one substance and work situation for another substance and/or work situation is currently not available. This study presents a framework for an extensive read-across of existing worker inhalable exposure measurement data. This framework enables the calculation of read-across factors based on another substance and/or work situation by first evaluating the quality of the existing measurement data and then mapping its similarity or difference with another substance and/or work situation. The system of read-across factors was largely based on the determinants in ECETOC TRA and ART exposure models. The applicability of the framework and its proof of principle were demonstrated by using five case studies. In these case studies, either the 75th percentiles of measured exposure data was observed to lie within the estimated 90% confidence intervals from the read-across approach or at least with the increase in the geometric mean of measured exposure, geometric mean of estimated exposure also increased. Testing and re-evaluation of the present framework by experts in exposure assessment and statistics is recommended to develop it further into a tool that can be widely used in exposure assessment and regulatory practices.
Abstract Several exposure assessment models use dustiness as an input parameter for scaling or estimating exposure during powder handling. Use of different dustiness methods will result in considerable differences in the dustiness values as they are based on different emission generation principles. EN17199:2019 offers 4 different dustiness test methods considering different dust release scenarios (e.g. powder pouring, mixing and gentle agitation, and vibration). Conceptually, the dustiness value by a given method can be multiplied with a scenario-specific modifier, called a handling energy factor (Hi), that allows conversion of a dustiness value to a release constant. Therefore, a Hi, scaling the effective mechanical energy in the process to the energy supplied in the specific dustiness test, needs to be applied. To improve the accuracy in predictive exposure modelling, we derived experimental Hi to be used in exposure algorithms considering both the mass- and number-based dust release fraction determined by the EN17199-3 continuous drop (CD) and the EN17199-4 small rotating drum (SRD) test methods. Three materials were used to evaluate the relationship between dustiness and dust levels during pouring powder from different heights in a controlled environment. The results showed increasing scatter and difference between the Hi derived for the 2 test methods with increasing pouring height. Nearly all the Hi values obtained for both SRD and CD were <1 indicating that the dustiness tests involved more energy input than the simulated pouring activity and consequently de-agglomeration and dust generation were higher. This effect was most pronounced in CD method showing that SRD mechanistically resembles more closely the powder pouring.
The NANOFOL concept aims at creating nanodevices containing a drug for inflammatory disorder treatment. This paper provides recommendations for nanosafety based on a measurement campaign which aimed at identifying exposure risks with respect to two specific phases of the products lifecycle, that is, production of the device and its waste management. The nanoparticles presence both in air and in liquid phase was studied. While no emissions were detected during the production period, many recommendations have been made, particularly regarding the nanowaste treatment, based on nanosafety guidelines. ; Eugenia Nogueira (SFRH/BD/81269/2011) holds scholarships from Fundacao para a Ciencia e a Tecnologia (FCT). The authors thank the EC for funding from the European Union Seventh Framework Programme (FP7/2007-2013) under Grant Agreement NMP4-LA-2009-228827 ...
Background The EU Horizon2020 "safe-by-design for Nano" (SBD4Nano) project aims to develop a tool to assist users in the safe-by-design process and decisions to reduce risk as a result from working with- or using newly developed products containing manufactured nanomaterials (MNs). Therefore, TNO set out to develop an easy-to-use quantitative exposure assessment tool that helps users with different levels of expertise to reduce the exposure from MNs following an integrated Tiered safe-by-design approach.
Method Based on previous projects, literature, expert knowledge, a Tiered set of model determinants and corresponding calculations were integrated into a conceptual model. Also, an exposure database based on the EU GRACIOUS template was created containing a large set of exposure measurements collected from diverse literature studies. Machine learning was applied to these exposure measurements to validate and refine the model. Lastly, a safe-by-design module was added to assist users modify their material or process design to reduce exposure.
Results An online tool is realized that will be freely available on https://diamonds.tno.nl/#neq. The NEQ offers a Tiered approach by smartly adapting the questions based on the depth of information the user can provide allowing anywhere between a Tier-1 and a Tier-2 approach. After answering questions, the user is presented an exposure estimate including uncertainty of the current design. The user is guided to enter a new design that reduces the exposure and/or its uncertainty.
Abstract Paint formulations are complex mixtures of both dissolved and particulate components, both organic and inorganic. Amorphous silica nanoparticles are included to make the paint layer dirt-repellent. Over entire life cycle of the paints containing such silica nanoparticles, however, their complex multicomponent composition may raise several concerns as to their hazard when exposed to humans and environment, notably due to the potential release of the incorporated nano-objects. To mitigate such concerns, several Safe-by-Design target specifications can be performed to provide revised/modified paint formulations with reduced potential risk. Within EU H2020 funded project, HARMLESS (grant agreement 953183), a specific industrial case study focuses on worker exposure measurement at the industrial production site of silane modified silica nanoparticles and consumer exposure measurement during sanding of the painted surfaces containing such silica nanoparticles. First results indicate that the tested paint samples (with and without silica nanoparticles) have strong tendencies to generate airborne nano-objects during their sanding. However, the fraction of silica in the overall chemical composition of the airborne nano-objects is currently being investigated. A fraction of the dust generated during the paint sanding is being analysed for its hazard via advanced in vitro approaches combined with a battery of toxicological endpoint analyses. Based on the results, if the exposure concentration of silica nanoparticles is found to be exceeding its nano reference value (i.e. 40,000 cm-3 TWA) and exhibits deleterious biological impact, the size and surface of silica nanoparticles will be modulated accordingly by keeping an optimum balance between their functionality and risk
Abstract Dustiness is a key parameter describing the ability of powder materials to generate dust during agitation. The main goal of this work was to generate and assess the scientific basis for the validation and applicability of 6 dustiness methods to nanomaterials, and development of a subsequent OECD testing guideline. Six dustiness methods (rotating drum, small rotating drum, continuous drop, vortex shaker, fluidizer and venturi) were subjected to an intra- and inter-laboratory comparison (ILC) in which 15 international laboratories participated. ILC tests were conducted for 6 materials (3 TiO2 and 3 SiO2) of different chemical natures and dustiness levels. Each participating laboratory conducted at least 3 replicates per material. Harmonization of procedures, methods and data treatment took place prior to testing. Results from the ILC were assessed considering the different reported metrics such as respirable mass and particle number dustiness index. Overall, the intralaboratory variability for the different methods and metrics was under 30%. Variation between laboratories was generally higher for respirable mass than particle number dustiness index. These variations were mostly attributed to differences in setups such as tubing length or instrumentation. All methods except the venturi, which was characteristic for presenting low differences between materials and opposed classification to the rest of the methods, showed relatively similar material ranking. For all methods and laboratories the calculated z-score (measure of the deviation of each laboratory from the true value) was <2 as based on ISO 13528, which indicates gratifying results. Funding: EU H2020 Research and Innovation Programme under Grant Agreement 814401.
Abstract There has been an increasing use of manufactured nanomaterials in industrial applications and consumer products. It has instigated concerns about the sustainability, risks and uncertainties regarding the interactions of the nanomaterials with humans and the environment. Consequently, significant resources in Europe have been invested into tool and method development to support risk mitigation and management, facilitating the research and innovation process of manufactured nanomaterials. Extended risk analysis, including socio-economic impact and sustainability assessment is moving the conventional risk-based approach towards a wider safety-and-sustainability-by-design perspective. Despite growing tool and method developments, the level of awareness and use by stakeholders is still limited. Regulatory compliance and acceptance, reliability and trust, user-friendliness and compatibility with the users' needs are important factors traditionally known to hinder their widespread use. Therefore, a framework is presented to quantify the readiness of different tools and methods towards their wider regulatory acceptance and downstream use by different stakeholders. The framework, developed within Gov4Nano, diagnoses barriers which hinder regulatory acceptance and wider usability of a tool/method based on their Transparency, Reliability, Accessibility, Applicability and Completeness (TRAAC framework). An online TRAAC tool is being developed within HARMLESS that will be freely available on https://diamonds.tno.nl/#traac. Fourteen tools and methods were assessed using the TRAAC framework as proof-of-concept. The results provide insights into any gaps, opportunities, and challenges in the context of each of the 5 pillars of the TRAAC framework.
Abstract Risk governance, sustainability and safety-by-design have high attention in current research projects and policy. In the EU H2020 Gov4Nano project, we refined the EU H2020 caLIBRAte phase-gate nano-risk innovation governance framework, its guidance and expanded the list of supporting risk governance tools. Stakeholder wishes were mapped from previous projects and consultations made within Gov4Nano and across the two other EU H2020 NMBP-13 governance projects (NANORIGO and RiskGone) and considered in the refinement. The revised framework considers three pre-defined phase-gate models for minor (fast-track/low risk), intermediate (medium risk) and novel (high-risk) developments. The guidance was further elaborated to direct users though sustainability and safety-by-design considerations and risk mitigation actions. ISO21505 was used as the backbone for the risk governance framework. The approach allows design of the specific nano-risk governance project and information requirements for decision-making. The list of recommended nano-risk governance tools was expanded and selected considering their reliability and performance. An important step in this process was an evaluation of tools made under the umbrella of the OECD (ENV/CBC/MONO(2021)23; ENV/CBC/MONO(2021)27/REV; ENV/CBC/MONO(2021)28; ENV/CBC/MONO(2021)29/REV) and development of a new tool assessment framework called TRAAC (Transparency, Reliability, Accessibility, Applicability and Reliability). Limitations in application domains remains an issue for future developments. The approach and tools are made accessible via a nano-risk governance portal produced by the three NMBP-13 projects (http://nanoriskgov.eu/). Funding: European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement 814401.
Abstract Dermal exposure is an important exposure route for occupational exposure and risk assessment. A fluorescence method has been developed to quantify occupational dermal exposure based on a visualization technique, using Tinopal SWN as a fluorescent tracer. The method was developed within the framework of a large experimental study, the SysDEA project. In SysDEA, dermal exposure was measured with different methods for 10 simulated exposure situations by sampling powder and liquid formulations containing Tinopal SWN on coveralls and patches and subsequently chemically analysing them. For the fluorescence method, photographs of exposed volunteers who performed the experiments were taken inside a room which consisted of an optimized arrangement of several UV irradiating tube light brackets, reflective and non-reflective backgrounds for maximum light diffusion and a camera. Image processing analysis software processed these photographs to obtain corresponding light intensity in terms of summed pixel values. To be able to estimate the amount of Tinopal SWN, 25% of the measured data from the SysDEA experiments were used to calibrate by correlating the summed pixel values from the photographs to actual measured exposure values using a second order regression model. For spraying both high and low viscosity liquids, showing uniformly distributed exposure patterns, strong Pearson correlation coefficients (R > 0.77) were observed. In contrast, the correlations were either inconsistently poor (R = −0.17 to 0.28 for pouring, rolling high viscosity liquid, manually handling objects immersed in low viscosity liquid and handling objects contaminated with powder), moderate (R = 0.73 for dumping of powder), or strong (R = 0.83 and 0.77 for rolling low viscosity liquid and manually handling objects immersed in high viscosity liquid). A model for spraying was developed and calibrated using 25% of the available experimental data for spraying and validated using the remaining 75%. Under given experimental conditions, the fluorescence method shows promising results and can be used for the quantification of dermal exposure for different body parts (excluding hands) for spraying-like scenarios that have a more uniform exposure pattern, but more research is needed for exposure scenarios with less uniform exposure patterns. For the estimation of exposure levels, the surface loading limit should be lower than 1.5░µg/cm2 (a lower limit could not be quantified based on experiments conducted in this study) on a large surface, like a coverall, which should be ideally perpendicular to the camera.
