Human Data for Skin Sensitization Method Evaluation
Establishing confidence in alternatives to animal use for identifying potential skin sensitizers requires high-quality reference data for evaluation of new approaches. As humans are the species of interest for regulatory testing, the ideal reference data will be derived from testing on humans.
To support the evaluation of non-animal approaches for skin sensitization assessment, NICEATM and the German Federal Institute for Risk Assessment (BfR) collected data from 1555 publications for 2277 human predictive patch tests (HPPTs). Data from two types of HPPT were included: the human repeat insult patch test and the human maximization test. Tests were scored for reliability and traced back to their original reports to remove duplicates. The resulting database contains information for 1366 unique substances. This database is being made available to serve as a resource for additional evaluation of alternative methods and development of new approach methodologies for skin sensitization assessments. Users may download the database in Excel format via the link below. Data are also available via NICEATM’s Integrated Chemical Environment.
Human predictive patch test database (updated May 25, 2023)
Evaluation of Skin Sensitization Classification Rules to Reflect Human Potency
NICEATM and BfR collaborators used the HPPT data set to develop an updated approach to classifying sensitizers that considers human potency. A poster describing this approach (Herzler et al., Regulation/Policy session) was presented at the 2023 annual meeting of the Society of Toxicology.
The United Nations Globally Harmonized System for Classification and Labelling of Chemicals (GHS) is used internationally for classification of hazardous substances, including skin sensitizers. Classifications are used to determine labeling statements, personal protective equipment requirements, and handling procedures.
Approaches currently used to subcategorize skin sensitizers into GHS subcategory 1A (“strong”) or 1B (“other than strong”) consider only the dose inducing the skin sensitization response and not the frequency of induced sensitization in human subjects. To address this limitation, the data set described above was used to conceptualize approaches that incorporate the number of sensitized subjects. Options explored included the dose per skin area (DSA) at which one subject is sensitized or the DSA at which 5% of subjects are sensitized. Both data types showed good concordance when compared to an overall weight-of-evidence consensus classification. This approach to classifying and subcategorizing sensitizers improves the prediction of potency while providing good reproducibility and concordance with animal reference data.