Aroma Ingredients

BASF Aroma Ingredients’ Safe-by-Design Process

In recent years, the SbD philosophy has broadened into the EU’s Safe and Sustainable by Design (SSbD) framework for chemicals and materials. In 2022, The European Commission published their first draft of the SSbD framework, which was commented and tested two years and resulted now in a voluntary guidance on how to steer innovation towards safe and sustainable chemicals and materials throughout the entire life cycle.¹In practice, this means applying guiding principles and iterative assessments of safety and sustainability during chemical, material or product design. For example, developers are urged to minimize both substances´ hazard profile and exposure impacts across its life cycle—from production to use to end-of-life. By building these considerations into innovation early one can assess the hazard, exposure and risk in the final use of this substance, substitute or eliminate substances of (high) concern where no safe use can be shown or where alternatives can be used and ensure new products have a better profile for health and the environment.

The SSbD framework recommends evaluating four key aspects in an iterative way: inherent hazard property of the chemical, human health and safety during the production of the chemical, environmental and human health risk during use phase and environmental impacts along the entire life cycle. Notably, this is currently a voluntary approach, but its application in innovation can improve a company’s readiness with regard to future legislation.

Since in many cases, sustainability data and harmonized approaches for criteria assessments are still missing, applying a Safe by Design concept addressing the hazard and risks during the innovation of a new chemical as described in EU Commissions SSbD Framework helps to develop regulatory future proof fragrances that will align with upcoming regulations and will be according to highest standards.

¹Abbate, E., Garmendia Aguirre, I., Bracalente, G., Mancini, L., Tosches, D., Rasmussen, K., Bennett, M.J., Rauscher, H. and Sala, S., Safe and Sustainable by Design chemicals and materials - Methodological Guidance, Publications Office of the European Union, Luxembourg, 2024, doi:10.2760/28450, JRC138035

BASF Aroma Ingredients has integrated the Safe‑by‑Design concept into a structured, multi‑phase innovation framework for the development of new fragrances. Throughout the entire R&D process—from the initial molecular concept to commercialization—defined safety assessment checkpoints are implemented. This systematic approach ensures the identification and advancement of candidate molecules that not only deliver the desired sensory properties but also exhibit robust toxicological and environmental profiles.

The prioritized hazard endpoints reflect the final use as consumer product in cosmetics and home care, with special focus not only on hazard endpoints leading to a classification as substances of very high concern, but also e.g. Skin Sensitization Cat 1 A and Persistency, which should be excluded in such applications.

Fig.1.: Safe by Design Checkpoints within the innovation chain process. The listed hazard endpoints do not have to necessarily follow this order and might also be addressed much earlier in the process, depending on initial in silico predictions.

Phase 1: In Silico Screening – “Safe-by-Design” Starts on the Drawing Board

At the beginning of the R&D process, an initial screening step employing computational (in silico) methods prior to the synthesis of any physical samples is performed. At this conceptual stage, toxicologists, ecotoxicologists and regulators collaboratively assess the proposed molecular structures using in silico tools.

This includes the application of QSAR (Quantitative Structure–Activity Relationship) models to predict potential hazard properties based on structural features, as well as read‑across approaches that draw on existing data from structurally related substances.

In addition, relevant scientific literature and regulatory safety databases are systematically reviewed to identify any indications of potential hazards, along with information on global regulatory status and registration requirements.

Most important hazard classes that would be showstoppers:

Carcinogenicity and/or mutagenicity (C/M),
Reproductive toxicity (R),
Endocrine disruption (ED),
Persistence, mobile or potential for bioaccumulation in combination with high environmental toxicity (PBT/PMT)
Application-specific important hazards like strong skin sensitization (Cat 1 A)

Any compound that shows high likelihood of classification in these categories gets scrutinized closely and if concerns are confirmed it is either dropped or re-designed early.

Phase 2: In Vitro & NAM Testing –From Computer to the Lab Bench

Once a new aroma candidate passes the initial in silico screening, the next phases involve actual experimentation to validate those predictions.
BASF will synthesize small samples of the most promising candidates and subject them to targeted in vitro tests and other New Approach Methodologies (NAMs). This typically happens during the lab phase and pilot phase of the project.

Key activities include:

AMES/HPRT/MNT/TGR in vitro test on mutagenicity
Skin Sensitization in vitro test battery on the potential to cause skin sensitization
Biodegradation in waste water to exclude potential persistency
Acute Ecotoxicity on daphnia and algae to exclude strong environmental toxicity
If needed, tailor-made strategies involving in vitro testing on Endocrine Activity, e.g. on potential estrogenic, androgenic or thyroid related activities

By the end of Phase 2, we aim to have a lead molecule that has sailed through both the in silico filters and the in vitro/NAM tests without significant issues.
In practice, this means the molecule should not be triggering any warnings for potential classification that are not suitable for the application as fragrance, surpassing also potential future regulations.

Phase 3: Comprehensive Evaluation & Selection – Regulatory Readiness

In the subsequent development stages (pilot phase and launch preparation), BASF conducts comprehensive testing and undertakes the required regulatory compliance activities for the selected candidate molecule.

At this point, the earlier screening phases have established a high level of confidence in the molecule’s suitability from both a perfumery and safety perspective, and the ensuing regulatory studies are expected to confirm an excellent toxicological and ecotoxicological profile. Potential identified hazard classifications are being verified and assessed in comprehensive and detailed risk assessments on the intended uses – with only safe to be used substances to be registered.

Depending on the intended application, appropriate registration processes—such as REACH—must be carried out, including the associated testing requirements. Where mandated by regional regulations, animal studies may be necessary and are performed in accordance with OECD test guidelines and GLP standards.

Overall, Phase 3 focuses on ensuring that the substance meets, and ideally exceeds, all current and anticipated regulatory requirements across relevant global markets (EU, US, Asia, etc.).

Thanks to the Safe-by-Design approach, this final validation usually does not produce any surprises in terms of regulatory compliance. This proactive workflow is explicitly aligned with future-facing criteria: for example, it anticipates upcoming changes like the European Chemicals Strategy for Sustainability (CSS), including screening on Endocrine Disruption or persistent substances.

By building those considerations in, the new ingredients are designed to be future-proof and regulator-ready.