Abstract
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.
Original language | English |
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Article number | 104688 |
Journal | Regulatory Toxicology and Pharmacology |
Volume | 116 |
DOIs | |
State | Published - Oct 2020 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2020 The Author(s)
Funding
Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R43ES026909. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R44ES026909. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R43ES026909 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number R44ES026909 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funders | Funder number |
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National Institutes of Health.Research | |
National Institutes of Health | |
National Institute of Environmental Health Sciences | R43ES026909 |
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