Advanced material development, including at the nanoscale, comprises costly and complex challenges coupled to ensuring human and environmental safety. Governmental agencies regulating safety have announced interest toward acceptance of safety data generated under the collective term New Approach Methodologies (NAMs), as such technologies/approaches offer marked potential to progress the integration of safety testing measures during innovation from idea to product launch of nanomaterials. Divided in overall eight main categories, searchable databases for grouping and read across purposes, exposure assessment and modeling, in silico modeling of physicochemical structure and hazard data, in vitro high‐throughput and high‐content screening assays, dose‐response assessments and modeling, analyses of biological processes and toxicity pathways, kinetics and dose extrapolation, consideration of relevant exposure levels and biomarker endpoints typify such useful NAMs. Their application generally agrees with articulated stakeholder needs for improvement of safety testing procedures. They further fit for inclusion and add value in nanomaterials risk assessment tools. Overall 37 of 50 evaluated NAMs and tiered workflows applying NAMs are recommended for considering safer‐by‐design innovation, including guidance to the selection of specific NAMs in the eight categories. An innovation funnel enriched with safety methods is ultimately proposed under the central aim of promoting rigorous nanomaterials innovation.

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The ECETOC TRA model (presently version 3.1) is often used to estimate worker inhalation and dermal exposure in regulatory risk assessment. The dermal model in ECETOC TRA has not yet been validated by comparison with independent measured exposure levels. This was the goal of the present study. Measured exposure levels and relevant contextual information were gathered via literature search, websites of relevant occupational health institutes and direct requests for data to industry. Exposure data were clustered in so-called exposure cases, which are sets of data from one data source that are expected to have the same values for input parameters in the ECETOC TRA dermal exposure model. For each exposure case, the 75th percentile of measured values was calculated, because the model intends to estimate these values. The input values for the parameters in ECETOC TRA were assigned by an expert elicitation and consensus building process, based on descriptions of relevant contextual information.From more than 35 data sources, 106 useful exposure cases were derived, that were used for direct comparison with the model estimates. The exposure cases covered a large part of the ECETOC TRA dermal exposure model. The model explained 37% of the variance in the 75th percentiles of measured values. In around 80% of the exposure cases, the model estimate was higher than the 75th percentile of measured values. In the remaining exposure cases, the model estimate may not be sufficiently conservative.The model was shown to have a clear bias towards (severe) overestimation of dermal exposure at low measured exposure values, while all cases of apparent underestimation by the ECETOC TRA dermal exposure model occurred at high measured exposure values. This can be partly explained by a built-in bias in the effect of concentration of substance in product used, duration of exposure and the use of protective gloves in the model. The effect of protective gloves was calculated to be on average a factor of 34 in this data set, while factors of five to ten were used in the model estimations. There was also an effect of the sampling method in the measured data on the exposure levels. Exposure cases where sampling was done via an interception method, such as gloves, on average showed a factor of six higher 75th percentiles of measured values than exposure cases where sampling was done via a removal method, such as hand washing. This may partly be responsible for the apparent underestimation of dermal exposure by the model at high exposure values. However, there also appeared to be a relation between expected exposure level (as indicated by the model estimate) and the choice of sampling method.In this study, solid substances used in liquid products were treated as liquids with negligible volatility. The results indicate that the ECETOC TRA dermal exposure model performs equally well for these substances as for liquids. There were suggestions of a difference in performance of the model between solids and liquids.For several parts of the ECETOC TRA der...

The aim of this study was to (a) develop a method for converting particle number concentrations (PNC) obtained by Dylos to PM2.5 mass concentrations, (b) compare this conversion with similar methods available in the literature, and (c) compare Dylos PM2.5 obtained using all available conversion methods with gravimetric samples. Data were collected in multiple residences in three European countries using the Dylos and an Aerodynamic Particle Sizer (APS, TSI) in the Netherlands or an optical particle counter (OPC, GRIMM) in Greece. Two statistical fitted curves were developed based on Dylos PNC and either an APS or an OPC particle mass concentrations (PMC). In addition, at the homes of 16 volunteers (UK and Netherlands), Dylos measurements were collected along with gravimetric samples. The Dylos PNC were transformed to PMC using all the fitted curves obtained during this study (and three found in the literature) and were compared with gravimetric samples. The method developed in the present study using an OPC showed the highest correlation (Pearson (R) = 0.63, Concordance (ρc) = 0.61) with gravimetric data. The other methods resulted in an underestimation of PMC compared to gravimetric measurements (R = 0.65‐0.55, ρc = 0.51‐0.24). In conclusion, estimation of PM2.5 concentrations using the Dylos is acceptable for indicative purposes.

There is a principal need for more precise methodology with regard to the determination of occupational dermal exposure. The goal of the Systematic analysis of Dermal Exposure to hazardous chemical Agents at the workplace project was therefore to generate scientific knowledge to improve and standardize measurement methods for dermal exposure to chemicals at the workplace. In addition, the comparability of different measurement methods was investigated. Different methods (body sampling by means of coveralls and patches, hand sampling by means of gloves and washing, and head sampling by means of headbands and wiping) were compared. Volunteers repeatedly performed a selection of tasks under standardized conditions in test chambers to increase the reproducibility and decrease variability. The selected tasks were pouring, rolling, spraying, and handling of objects immersed in liquid formulations, as well as dumping and handling objects contaminated with powder. For the chemical analysis, the surrogate test substance Tinopal SWN was analyzed by means of a high-performance liquid chromatographic method using a fluorescence detector. Tinopal SWN was either applied as a solid product in its pure form, or as a low and high viscosity liquid containing Tinopal SWN in dissolved form. To compare the sampling methods with patches and coveralls, the exposure values as measured on the patches were extrapolated to the surface areas of the respective parts of the coverall. Based on this extrapolation approach, using the patch method resulted in somewhat higher exposure values compared to using a coverall for all exposure situations, but the differences were only statistically significant in case of the liquid exposure situations. Using gloves resulted in significantly higher exposure values compared to hand wash for handling immersed objects, rolling, and handling contaminated objects, and slightly higher (not significant) exposure values during pouring and spraying. In the same context, applying wipe sampling resulted in higher exposure values than using a headband, which was at least partly due to extrapolation of the wipe results to the surface area of the headband. No ‘golden standard’ with regard to a preferred measurement method for dermal exposure could be identified from the methods as investigated in the current study.

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.

For many work situations only insufficient exposure data are available to perform proper risk assessment. Because measuring worker exposure can be time consuming and resource intense, the availability of reliable exposure models is important when performing risk assessments. However, the development and improvement of exposure models are hampered by scarcity of sound exposure data as well as by lack of information on relevant exposure factors and conditions of exposure. This paper describes a study where inhalation and dermal exposure data were collected under defined conditions. Exposure scenarios examined included tasks that have not been investigated in previous validation studies. The results of these measurements were compared with ECETOC TRA model version 3.1 predictions. In this study, five exposure scenarios were selected, namely ‘use in a closed batch process’ (PROC 4), ‘mixing or blending in a partly open batch process’ (PROC 5), ‘rolling’ (PROC 10), ‘immersion’ (PROC 13), and ‘stirring’ (PROC 19). These PROCs stem from the descriptors that Registration, Evaluation and Authorization of Chemicals has established to depict the identified uses of chemical substances. These exposure scenarios were selected mainly because little or no data are available for these situations, or ECETOC TRA is likely to underestimate exposure for these situations. Experiments were performed by volunteers for the selected exposure scenarios, in which tasks were performed aiming to represent real workplace situations. In total 70 experiments were performed, during which 70 dermal exposure measurements (5 volunteers × 2 repeats × 7 scenarios) and 32 inhalation exposure measurements (4 volunteers × 2 repeats × 4 scenarios) were collected. Two formulations were used, namely pure Tinopal SWN powder (solid product, a fluorescent tracer) and 0.5% Tinopal SWN dissolved in 1,2-dichloroethane (1,2-DCE). DCE is considered a moderate volatile liquid. For exposure scenarios using the liquid formulation, both inhalation and dermal measurements were performed, while for exposure scenarios using the pure powder only dermal exposure measurements were performed. In addition, photographs were taken under ultraviolet light to qualitatively assess exposure patterns on hands and body. Volunteers repeatedly performed a selection of tasks under standardized conditions in a test chamber for each exposure scenario. Results show that ECETOC TRA overestimated dermal hand exposure for all PROCs included in the study, and was considered to be conservative. Additionally, ECETOC TRA overestimated inhalation exposure for closed and partially closed processes, but underestimated inhalation exposure for rolling and handling of immersed objects. Qualitative assessment of the hands and body showed mainly the hands were exposed for tasks involving closed and partially closed processes and when handling of immersed objects. Exposure to other body segments were also observed for rolling and stirring. In conclusion, this study gave insights into dermal and inhalation exposure levels during selected task scenarios, and showed that ECETOC TRA is conservative when dermal exposure is estimated. Inhalation exposure estimates for PROCs 10 and 13 tasks with the moderate volatility liquid were underestimated in this study. It may be therefore necessary to re-evaluate base model predictions for these scenarios when medium fugacity liquids are involved.

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