A practical decision-making approach for tiered in silico chemical hazard assessment based on the safe and sustainable by design framework

Authors: Karolina Jagiello, Szymon Zdybel, Anita Sosnowska, Karina Kunikowska, Benjamin Punz, Martin Himly, Haralambos Sarimveis, Philip Doganis, Maria Rivero, Carlos Fito, Tomasz Puzyn 

Publication date: October 2026

DOI: https://doi.org/10.1016/j.envint.2026.110527

Language: English

Abstract: The “Safe and Sustainable by Design” (SSbD) approach promotes the development of chemicals that are inherently safer and more sustainable, including viable alternatives to hazardous substances. It involves assessing the toxicity, environmental impact and functionality of potential substitutes to ensure that they meet performance requirements without compromising safety. In silico methods using computational tools and simulations support the SSbD approach by predicting the toxicity, environmental persistence and performance of potential substitutes prior to upscaling in physical testing. This approach intends to accelerate the design process, reduce costs on the long run and improve safety and sustainability through the early identification of and optimisation towards safer and more sustainable chemicals and materials. Surfactants (SFs) and flame retardants (FRs) are among the many areas of interest to regulators and scientists across various industries. Due to the massive growth of global markets resulting from a wide range of their applications, and evidence of the adverse impact on the environment and human health, there is a pressing need to accelerate the design and implementation of safer alternatives for those chemicals. In this paper, we present an intuitive and harmonised workflow on how the use of quantitative structure–activity relationship (QSAR) −based in silico tools for preliminary hazard assessment and data gap filling, in accordance with the SSbD multi-tiered approach. We illustrate the practical application of these guidelines through three case studies that reflect realistic scenarios encountered by SSbD practitioners during chemical safety assessment. A harmonised, step-by-step decision-making process, supported by flowcharts included in our decision-making framework for Tier 0 and 1 Hazard Identification in regard of the Joint Research Centre (JRC)’s updated SSbD framework, enables users to assess the hazards associated with a given chemical substance in accordance with the most important and up-to-date regulations in force within the European Union (EU).

Keywords: In silico; Framework; SSbD; Hazard assessment; Computational tools