Reporter Skin: Skin Sensitization Assessment Options for Lipophilic Compounds, Mixtures and Polymers

Challenge and solution approach

New pharmaceuticals, cosmetics, and chemicals must be tested for consumer safety before they are made available on the market. Animal testing for cosmetics has been banned throughout the EU since 2013. Consequently, there is a great need for reliable alternative methods that do not involve animal testing—especially for mixtures, extracts, and lipophilic compounds, which play an important role in the cosmetics industry. Existing New Approach Methodologies (NAMs), as animal-free alternative methods are called, are often unable to reliably evaluate the ability of such substances to induce skin sensitizing effects. In addition, the low water solubility of lipophilic substances makes it difficult to test these substances in accordance with OECD guidelines. New strategies to evaluate their skin sensitization potential are therefore urgently needed.

A promising new test system—completely free of media additives of animal origin—is the Nrf2 reporter epidermis model, which was developed at Fraunhofer IGB in collaboration with cosmetics specialist Beiersdorf AG and was awarded the City of Hamburg's Research Prize for the Promotion of the Development of Alternative and Complementary Methods to Animal Testing in 2024.

Objectives and project plan

By inducing the Nrf2 signaling pathway, the patented in-vitro model (WO-2013092480-A1) addresses the detection of the skin-sensitizing effect of substances via the regulatory-approved “Key Event 2” of the Adverse Outcome Pathway for skin sensitization.

The study commissioned by the International Collaboration on Cosmetics Safety (ICCS) is currently investigating the use of the 3D Nrf2 reporter epidermis model to test challenging compounds. The project focuses on developing testing options for compounds that fall beyond the scope of recognized OECD tests (e.g., lipophilic compounds, polymers, mixtures).

In the initial phases of the project, the predictive power of the method was demonstrated using individual substances—in particular those that yield unreliable or erroneous (false positive/false negative) results in tests based on suspension cell cultures.

Impact and outlook

In-vitro reporter skin models provide very precise results when testing substances used in cosmetics, as they have key skin characteristics such as barrier and metabolic functions, enabling test conditions that closely resemble in-vivo conditions. They also allow the simultaneous analysis of several parameters at different time points , enabling a comprehensive and well-founded risk assessment.

In addition to evaluating existing methods such as EpiSensA (OECD TG 442D) and refining statistical approaches, the project therefore also aims at developing new approaches to apply OECD-validated concepts to mixtures, extracts, and lipophilic substances.