Bio: Isabelle Lee is a Senior Scientist at RIFM (the Research Institute for Fragrance Materials). She earned her PhD in Pharmacology at the University of Pennsylvania and has a keen interest in advancing the development of New Approach Methodologies (NAMs) for the safety assessment of consumer product ingredients. Dr. Lee joined RIFM in 2020 and currently leads the skin sensitization team, overseeing the safety assessment and research programs.

Abstract: Evaluating ingredients’ potential to induce skin sensitization is crucial in safety assessments. The dermal sensitization threshold (DST), similar to the threshold of toxicological concern (TTC), was developed to assess materials with low skin exposure. The first DST was developed based on Local Lymph Node Assay (LLNA) data and was applied to chemicals not considered to be reactive to skin proteins, which is the molecular initiating event of skin sensitization. A DST of 900 μg/cm² was derived for these chemicals. Later, the DST concept was extended to protein-reactive chemicals, and a threshold of 64 μg/cm² was derived for reactive materials. This DST protects against 95% of protein-reactive chemicals, minimizing skin sensitization risk below the threshold. Structural chemistry rules were created to identify highly reactive materials, leading to a DST of 1.5 μg/cm² for high-potency chemical. Preliminary work on complex mixtures, such as botanical extracts, led to a mixture DST of 6010 μg/cm² for materials found to be negative in in vitro skin sensitization assays. With expanded LLNA data and the in silico expert system Derek Nexus, reactive and non-reactive DSTs were updated to 73 μg/cm² and 710 μg/cm², respectively. These DST thresholds support exposure-based waiving for materials with low dermal exposure.