Hosted by the SOT Dermal Toxicology Specialty Section
Join us as Dr. Hervé Groux (ImmunoSearch) and Dr. Isabelle Lee (Research Institute for Fragrance Materials) present their work on NAMs and in vitro testing in the field of skin sensitization assessment.
Hervé Groux, DVM, PhD, CEO and CSO, ImmunoSearch
The assessment of skin sensitization potential in complex mixtures, such as cosmetic products and medical device extracts, presents distinct scientific and regulatory challenges. While validated in vitro methods have significantly advanced for individual substances, their application to mixtures requires careful consideration of formulation effects, irritancy, and potential chemical interactions.
The SENS-IS assay, based on a transcriptomic approach using reconstructed human epidermis, offers a robust tool for addressing these complexities. A catch-up study supporting the use of a newly developed in-house 3D epidermis model is currently under evaluation by the OECD, further reinforcing the assay's relevance for regulatory use.
Our published work (2019) demonstrated that SENS-IS can identify a variety of mixture-related effects, including vehicle-dependent modulation of sensitization potency, irritant-induced enhancement, additive or synergistic interactions at low concentrations, and positive responses in finished consumer products. Since then, the assay has been applied to a wide range of mixtures, supporting its applicability across different regulatory contexts.
This presentation will focus on recent case studies involving cosmetic products, illustrating how formulation components can significantly influence the sensitization profile of active substances. To expand the assay’s relevance, we are also evaluating a complementary full-thickness skin model that incorporates a dermal compartment. This system more closely mimics native skin architecture and offers new insights into mixture effects involving deeper skin layers. Together, the epidermal and full-thickness models enhance the utility of the SENS-IS assay in mixture testing, contributing valuable data for risk assessment
Isabelle Lee, PhD, Manager, Human Health Safety & Strategy, Research Institute for Fragrance Materials
Quantitative risk assessment (QRA) for dermal sensitization is critical in establishing safe use levels of sensitizing ingredients in consumer products. Traditionally, QRA relies on the No Expected Sensitization Induction Level (NESIL) as the point of departure (PoD), often determined through human testing via the Confirmation of No Induction in Humans (CNIH) repeat patch test. However, with the advancement of New Approach Methodologies (NAMs) and their integration into Next Generation Risk Assessment (NGRA) frameworks, industry is moving toward not only non-animal, but also non-human testing strategies for PoD derivation.
Significant progress has been made in applying NAMs to discrete chemicals, but challenges remain in evaluating natural complex substances (NCS) and other mixtures due to their multiconstituent and variable nature. In the fragrance industry, many NCS contain known discrete components, enabling a component-based risk assessment approach. However, this strategy is not universally applicable, prompting exploration of NAM-based methods for direct PoD derivation.
This presentation highlights the use of several quantitative potency-based NAMs, which may include Bayesian models like SARA and SARA-ICE, the GARDskin dose-response assay, and OECD in vitro regression models, to support risk assessment of NCS and mixtures. Within the NGRA framework, these methods allow for the derivation of a NAM-based PoD, which can be adjusted using uncertainty factors to estimate a predicted NESIL (pNESIL). This value is then used to calculate Acceptable Exposure Levels (AELs) for consumer products such as deodorants and bar soaps, which are compared against estimated Consumer Exposure Levels (CELs) to determine the margin of safety.
Case studies will be presented to demonstrate how currently available NAMs can be effectively used in NGRA to assess NCS, offering a scientifically robust alternative to traditional animal and human testing for QRA.