Leadscope, Inc, 1393 Dublin Rd, Columbus, OH, 43215, USA.
Bioinformatics Department, The University of Uppsala, 752 36, Uppsala, Sweden.
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.
皮肤致敏评估在过去几年中不断发展，包括对不良结局途径关键事件的体外评估，并利用计算方法的优势来支持证据权重评估，而无需在动物中进行测试。虽然计算方法在目的和格式上有很大差异，但需要标准化开发此类模型的基本原则，并明确对整体评估不确定性的影响。在本贡献中，皮肤致敏相关效应、机制和终点之间的关系被构建到危害评估框架中。基于机制和效应的相关性以及用于识别它们的实验系统的优势和局限性，定义了用于推导皮肤致敏计算评估的规则和原则。此外，还讨论了反映评估整体强度的可靠性和置信度评分的分配。该皮肤致敏方案支持计算方法在预测皮肤致敏中的实施和接受。
