关键词: Computational prediction Data integration Defined approaches Non-animal methods Skin sensitization

Mesh : Animals Humans Mobile Applications Animal Testing Alternatives / methods Skin Dermatitis, Allergic Contact / etiology

来  源:   DOI:10.1186/s12859-023-05617-1   PDF(Pubmed)

Abstract:
BACKGROUND: Chemically induced skin sensitization, or allergic contact dermatitis, is a common occupational and public health issue. Regulatory authorities require an assessment of potential to cause skin sensitization for many chemical products. Defined approaches for skin sensitization (DASS) identify potential chemical skin sensitizers by integrating data from multiple non-animal tests based on human cells, molecular targets, and computational model predictions using standardized data interpretation procedures. While several DASS are internationally accepted by regulatory agencies, the data interpretation procedures vary in logical complexity, and manual application can be time-consuming or prone to error.
RESULTS: We developed the DASS App, an open-source web application, to facilitate user application of three regulatory testing strategies for skin sensitization assessment: the Two-out-of-Three (2o3), the Integrated Testing Strategy (ITS), and the Key Event 3/1 Sequential Testing Strategy (KE 3/1 STS) without the need for software downloads or computational expertise. The application supports upload and analysis of user-provided data, includes steps to identify inconsistencies and formatting issues, and provides predictions in a downloadable format.
CONCLUSIONS: This open-access web-based implementation of internationally harmonized regulatory guidelines for an important public health endpoint is designed to support broad user uptake and consistent, reproducible application. The DASS App is freely accessible via https://ntp.niehs.nih.gov/go/952311 and all scripts are available on GitHub ( https://github.com/NIEHS/DASS ).
摘要:
背景:化学诱导的皮肤致敏,或者过敏性接触性皮炎,是一个常见的职业和公共卫生问题。监管当局要求对许多化学产品引起皮肤致敏的可能性进行评估。定义的皮肤致敏方法(DASS)通过整合来自基于人类细胞的多个非动物试验的数据来识别潜在的化学皮肤致敏剂,分子靶标,和使用标准化数据解释程序的计算模型预测。虽然一些DASS在国际上被监管机构接受,数据解释程序的逻辑复杂性各不相同,和手动应用程序可能是耗时的或容易出错。
结果:我们开发了DASS应用程序,一个开源的Web应用程序,为了方便用户应用三种皮肤致敏评估的监管测试策略:三分之二(2o3),综合测试战略(ITS),和关键事件3/1顺序测试策略(KE3/1STS),无需软件下载或计算专业知识。该应用程序支持上传和分析用户提供的数据,包括识别不一致和格式问题的步骤,并以可下载的格式提供预测。
结论:这种针对重要公共卫生终点的基于网络的开放获取国际协调监管指南的实施旨在支持广泛的用户采用和一致的,可重复的应用。DASS应用程序可通过https://ntp免费访问。Niehs.nih.gov/go/952311和所有脚本都可以在GitHub(https://github.com/NIEHS/DASS)上找到。
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