Next generation risk assessment (NGRA) is exposure-led, hypothesis driven, and designed to prevent harm. The principles underpinning NGRA for cosmetic ingredients have been described by the International Cooperation on Cosmetics Regulation, and several tools are available to conduct such an assessment. These range from exposure-based waiving and read across to in silico and in vitro approaches. This talk will focus on work being conducted to progress ab initio NGRA for systemic toxicity, where exposures exceed the threshold of toxicological concern and there are no structural analogues with existing data. In this type of assessment, measures of bioactivity generated using a broad suite of in vitro approaches are compared with internal exposure estimates made using physiologically-based kinetic models. Examples will be given to help put the resulting bioactivity:exposure ratios (BERs) into context for robust and pragmatic decision making.

The Threshold of Toxicological Concern (TTC) is a risk assessment tool, establishing human exposure threshold values for chemicals below which there is a very low probability of risk of systemic adverse effects to human health. It is applicable for compounds for which chemical structure and exposure data are available, but no toxicity data. Substances are grouped into three Cramer classes of which only Class I (46 μg/kg bw/d) and Class III (2.3 μg/kg bw/d) are accepted by the Scientific Committee on Consumer Safety (SCCS/1628/21). For compounds with a genotoxic alert a threshold value of 0.0025 µg/kg bw/d is set. TTC is applicable on a case-by-case basis for impurities or added substances. TTC gained importance for cosmetic ingredients seen the testing and marketing bans in the EU. In the Next Generation Risk Assessment workflow (taken up in the SCCS Notes of Guidance), TTC offers an exit in tiers 0 and 1.

Due to increasing environmental concerns, local regional regulations are put in place. In Europe, within the European Green Deal, the Chemicals Strategy for Sustainability (CSS) sets the objective of a Toxic-Free Environment by substituting substances having a chronic effect for human health or the environment. New environmental hazard categories will therefore be added to the existing ones, e.g. endocrine disruptors or PMT (Persistent, Mobile and Toxic) substances.

The industry will need to fulfil new requirements linked to these new categories, keeping in mind that the cosmetic industry should ensure that its ingredients are not harmful for living organisms without tests on vertebrates.

L’Oréal and ICCS (International Collaboration on Cosmetics Safety) are actively involved in the method development to better assess and reduce the environmental impact of our ingredients and formulas, e.g. to assess the potential endocrine activity or the bioaccumulation of cosmetic ingredients.