Development of a skin sensitization Site-of-Contact Exposure Threshold (SoCET) for botanicals and natural substances

The concept of identifying threshold exposures to chemicals below which the risk to human health is negligible was originally proposed in the late 1960's. The induction of skin sensitization has been shown to demonstrate a dose response, and thus, a threshold concentration, or exposure, required to induce sensitization can be derived. The idea of a Dermal Sensitization Thresholds (DST) for chemicals has been investigated since 2008. However, DST developments have so far focused on individual sensitizing chemicals, rather than complex mixtures or botanical or naturally derived substances (BNS). With an increased interest in the use of BNS, which often contain low levels but unidentified sensitizing substances, the development of a sensitization threshold for BNS could support their safety assessments. In this work, we propose a site-of-contact exposure threshold (SoCET) of 10 μg/cm² for BNS using a constituent-based approach and demonstrate that it would be protective in a risk assessment against the induction of skin sensitization. The 10 μg/cm² SoCET can be used as the exposure-based waiving threshold in Tier 0 of the skin sensitization Next Generation Risk Assessment (NGRA) framework for BNS.