推进系统毒性风险评估:评估基于NAM的工具箱方法
Sophie Cable1, Maria Teresa Baltazar1, Fazila Bunglawala1
1Safety and Environmental Assurance Centre (SEAC), Unilever, Colworth Science Park, Sharnbrook MK44 1lQ, United Kingdom.
概括
无动物系统性毒性安全评估现在可以使用新方法方法 (NAM) 来实现. 一个开发的基于NAM的工具箱证明了对人类健康的保护超过90%,减少了对动物的试验.
科学领域:
- 毒理学 毒理学 毒理学
- 计算化学的计算化学
- 监管科学 监管科学
背景情况:
- 传统的系统性毒性动物试验是资源密集型的,并且在道德上受到争议.
- 新兴的in silico,in chemico和in vitro方法,称为新方法方法 (NAM),提供了替代方案.
- 与动物研究相比,确保同等或更高的保护对于采用NAM至关重要.
研究的目的:
- 开发和评估基于NAM的"工具箱",用于系统毒性安全评估.
- 评估基于NAM的方法的保护能力和效用.
- 为了促进向无动物安全评估的过渡.
主要方法:
- 开发一个整合生理基动力学 (PBK) 模型和生物活性 NAM 的工具箱.
- 计算生物活性:暴露比,以估计内部暴露率.
- 扩大最初的试点研究,包括38种额外的化学品和70种消费者暴露场景.
主要成果:
- 基于NAM的工作流显示,在测试的化学品和情景中,对人类健康的保护超过90%.
- 生物活性:暴露比率有效地为系统毒性做出决策提供了信息.
- 该研究验证了基于NAM的工具箱对于无动物安全评估的实用性.
结论:
- 基于NAM的系统性毒性安全评估工具箱在很大程度上保护了人类健康.
- 这种方法使得无动物安全决策成为可能,大大减少了动物使用.
- 确定了进一步的改进,以提高基于NAM的方法论的稳定性和信心.
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