(662d) A Computational Toolbox Supporting the Development of Safe and Sustainable By Design Chemicals and Materials

The European Union (EU), through the Chemicals Strategy for Sustainability (CSS) and the Zero Pollution Action Plan, has emphasized the imperative for an environment and economy that are both climate-neutral and toxic-free. This emphasis underscores a transition towards a Safe and Sustainable by Design (SSbD) approach, by integrating safety and sustainability considerations into the early design stages of chemicals and materials, focusing on the whole life cycle. SSbD aims to foster the chemical innovation process by developing and assessing novel and existing chemicals. This is achieved by adhering to circular economy principles, all while mitigating the potential negative impacts on human health, the environment and society in the short and long term. The EC introduced a framework for SSbD, which is a comprehensive five-step approach for the safety and sustainability assessment of chemicals and materials. The first three steps involve safety assessment including hazard, occupational exposure, environmental exposure, and consumer exposure. The last two steps are related to the sustainability assessment, including environmental and socioeconomic aspects.

Within the EU partnership on chemical risk assessment (PARC), the PARC SSbD toolbox is being developed. The PARC toolbox aims at the operationalization of the EC framework, by providing an integrative and innovation toolbox for both innovators and regulators. It will include all the relevant data, methods, and tools for SSbD, along with automated pipelines that encompass every step of the framework across the stages of innovation. The tools will be structured and mapped in accordance with the stages of chemical or material development into a phased commercial product development (stage-gate model) and the five steps of the EC framework. The PARC toolbox is based upon a methodological framework (in development) that leverages advanced methods for hazard, exposure, human health risk assessment, and sustainability assessment. Initiating from user-provided data, including chemical structure parameters and a designated parameter list, a range of tools with varying levels of complexity will be employed to facilitate the SSbD assessment across the innovation process.

The development of the alpha version of the toolbox is currently underway. As part of this development process, a detailed case study was conducted to explore the toolbox's full potential and to discern any disparities in the findings between the two stages as well as between the different tools used. The case study included the assessment of Bisphenol-A (BPA) and two potential alternative substances: Bisphenol-AP and Isosorbide. The selected substances underwent evaluation in two distinct applications: as a BPA alternative for polycarbonate bottles and as a BPA replacement in epoxy resin paints. To determine the efficiency of the toolbox, the case study was conducted in both the early and late stages of innovation. In early innovation, only the structure and the potential application of the substance were considered as input information. In the context of late innovation, the assessment process was informed by data derived from pertinent databases (e.g. ECHA Database, EFSA, PubChem, CompTox Chemical Dashboard) or from relevant studies. In both scenarios, a range of tools were used to perform the SSbD assessment.

In early innovation, Quantitative structure-activity relationship (QSAR) models, such as VEGA, OECD QSAR toolbox, Janus, Oncologic, Mistra SafeChem in silico Toolbox and Danish (Q)SAR database, were applied in Step 1 to predict the hazard endpoints (e.g., carcinogenicity, mutagenicity, reproductive toxicity, endocrine disruption) requested in the EC JRC framework. In Steps 2 (manufacturing and processing phase) and 3 (use phase), a number of models, including ECETOC TRA, ProScale, ART, Stoffenmanager, INTEGRA, ConsExpo, SimpleBox, CEM and Vermeer FCM, were employed to forecast potential risks relating to occupational, environmental, and consumer exposure. These models were used in both early and late innovation, and it was found that there were differences in their outcomes. The observed difference in the results between the early and late stages of innovation can be attributed to the source of input data used. Specifically, the former relied on QSAR predictions, while the latter was based on experimental measurements. In Step 4, a preliminary Life Cycle Assessment (LCA) was conducted to evaluate the environmental sustainability in early innovation. This assessment was performed using the GaBi LCA software, which is a widely recognized tool for conducting LCAs. Lastly, the exploration of Step 5, the socioeconomic analysis step, was very limited.

Overall, QSAR models, played a vital role in predicting hazards and physicochemical properties during early innovation when data availability was limited. In addition, variations in SSbD scores for Steps 1-3 were observed, with the selection of QSARs and the available data level influencing the results. Therefore, it is of great importance to evaluate the reliability of predictions resulting from QSARs and to perform an uncertainty analysis of the results from different tools. As a result, integrating New Approach Methodologies (NAMs) with QSARs to assess hazard potency is highly significant. Moreover, a need for further development of models for endocrine disruption and immunotoxicity prediction is highlighted. Finally, it is crucial to develop, test, and incorporate reliable predictive models for toxicity and tools for prospective LCA and socioeconomic assessment. In particular for LCA in early innovation, the lack of data regarding up- and downstream life cycle stages contributes to results uncertainty, and better guidance on how to populate the model is required.

In conclusion, the concept of SSbD is characterized by a high level of complexity arising from the diverse types of assessments essential for its implementation. This study has established a basis for the further refinement of the SSbD toolbox, aiming to enhance its efficacy and applicability and eventually foster cohesion across diverse policies and strategies. The SSbD toolbox will be a guidance tool that will include all the relevant data, tools, and methods for the operationalization of SSbD while focusing on the integration of risk and sustainability assessment.