The dermal sensitization threshold (DST) approach for mixtures evaluated as negative in <i>in vitro</i> test methods; mixture DST

• DOI: 10.2131/jts.44.23
• Publication Date: 2019-01-07T23:07:57Z
• Authors: Taku Nishijo; Masaaki Miyazawa; Kazutoshi Saito; Yuki Otsubo; Hideyuki Mizumachi; Hitoshi Sakaguchi
• Keywords: 0301 basic medicine; 0303 health sciences; Dose-Response Relationship, Drug; Cosmetics; Allergens; Administration, Cutaneous; Risk Assessment; 01 natural sciences; Cell Line; 03 medical and health sciences; Mice; Dermatitis, Allergic Contact; Animals; Humans; Drug Interactions; Haptens; Skin Tests; 0105 earth and related environmental sciences

Cosmetic ingredients often comprise complex mixtures, such as botanical extracts, which may contain skin sensitizing constituents. In our previous study for the sensitivity of evaluations constituents in mixtures using binary vitro test battery with KeratinoSensTM and h-CLAT, some sensitizers showed higher detection limits methods than murine local lymph node assays (LLNA). Thus, to minimize uncertainty associated decreased these sensitizers, a risk assessment strategy was developed negative results from battery. Assuming that no expected sensitization induction level (mixture NESIL) can be derived results, we assessed 146 LLNA data according assumption indeterminate mixtures. Finally, calculated 95th percentile probabilities mixture NESILs dermal thresholds DST) 6010 μg/cm2. Feasibility studies indicated this approach practical assessments products cosmetic industry. This would novel incorporating DST information methods.