Skin sensitization in silico protocol

Regul Toxicol Pharmacol. 2020 Oct;116:104688. doi: 10.1016/j.yrtph.2020.104688. Epub 2020 Jul 1.


The assessment of skin sensitization has evolved over the past few years to include in vitro assessments of key events along the adverse outcome pathway and opportunistically capitalize on the strengths of in silico methods to support a weight of evidence assessment without conducting a test in animals. While in silico methods vary greatly in their purpose and format; there is a need to standardize the underlying principles on which such models are developed and to make transparent the implications for the uncertainty in the overall assessment. In this contribution, the relationship between skin sensitization relevant effects, mechanisms, and endpoints are built into a hazard assessment framework. Based on the relevance of the mechanisms and effects as well as the strengths and limitations of the experimental systems used to identify them, rules and principles are defined for deriving skin sensitization in silico assessments. Further, the assignments of reliability and confidence scores that reflect the overall strength of the assessment are discussed. This skin sensitization protocol supports the implementation and acceptance of in silico approaches for the prediction of skin sensitization.

Keywords: (Q)SAR; Computational toxicology; Computational toxicology protocols; Defined approach; Expert alerts; Expert review; Extractables and leachables; In silico; In silico toxicology; Integrated approaches to testing and assessment (IATA); Skin sensitization.

MeSH terms

  • Allergens / toxicity*
  • Animal Testing Alternatives
  • Animals
  • Computer Simulation
  • Dendritic Cells / drug effects
  • Dermatitis, Contact / etiology
  • Haptens / toxicity*
  • Humans
  • Keratinocytes / drug effects
  • Lymphocytes / drug effects
  • Risk Assessment / methods*


  • Allergens
  • Haptens