German Federal Institute for Risk Assessment (BfR), Berlin, Germany.
German Federal Institute for Risk Assessment (BfR), Berlin, Germany; National Research Council, Ancona, Italy.
Environ Int. 2023 Aug;178:108082. doi: 10.1016/j.envint.2023.108082. Epub 2023 Jul 4.
The predominantly animal-centric approach of chemical safety assessment has increasingly come under pressure. Society is questioning overall performance, sustainability, continued relevance for human health risk assessment and ethics of this system, demanding a change of paradigm. At the same time, the scientific toolbox used for risk assessment is continuously enriched by the development of "New Approach Methodologies" (NAMs). While this term does not define the age or the state of readiness of the innovation, it covers a wide range of methods, including quantitative structure-activity relationship (QSAR) predictions, high-throughput screening (HTS) bioassays, omics applications, cell cultures, organoids, microphysiological systems (MPS), machine learning models and artificial intelligence (AI). In addition to promising faster and more efficient toxicity testing, NAMs have the potential to fundamentally transform today's regulatory work by allowing more human-relevant decision-making in terms of both hazard and exposure assessment. Yet, several obstacles hamper a broader application of NAMs in current regulatory risk assessment. Constraints in addressing repeated-dose toxicity, with particular reference to the chronic toxicity, and hesitance from relevant stakeholders, are major challenges for the implementation of NAMs in a broader context. Moreover, issues regarding predictivity, reproducibility and quantification need to be addressed and regulatory and legislative frameworks need to be adapted to NAMs. The conceptual perspective presented here has its focus on hazard assessment and is grounded on the main findings and conclusions from a symposium and workshop held in Berlin in November 2021. It intends to provide further insights into how NAMs can be gradually integrated into chemical risk assessment aimed at protection of human health, until eventually the current paradigm is replaced by an animal-free "Next Generation Risk Assessment" (NGRA).
以动物为中心的化学安全评估方法已逐渐受到压力。社会对该体系的整体性能、可持续性、对人类健康风险评估的持续相关性和伦理提出质疑，要求改变范式。与此同时，用于风险评估的科学工具包不断通过“新方法方法”（NAMs）的发展而得到丰富。虽然这个术语并没有定义创新的年龄或准备状态，但它涵盖了广泛的方法，包括定量构效关系（QSAR）预测、高通量筛选（HTS）生物测定、组学应用、细胞培养、类器官、微生理系统（MPS）、机器学习模型和人工智能（AI）。除了有希望更快、更有效地进行毒性测试外，NAMs 还有可能通过允许在危害和暴露评估方面更具人类相关性的决策，从根本上改变当今的监管工作。然而，一些障碍阻碍了 NAMs 在当前监管风险评估中的更广泛应用。解决重复剂量毒性的限制，特别是慢性毒性，以及相关利益相关者的犹豫，是在更广泛的背景下实施 NAMs 的主要挑战。此外，还需要解决可预测性、重现性和量化问题，并调整监管和立法框架以适应 NAMs。本文提出的概念观点侧重于危害评估，并基于 2021 年 11 月在柏林举行的研讨会和讲习班的主要发现和结论。它旨在进一步了解如何逐步将 NAMs 纳入旨在保护人类健康的化学风险评估，直到最终当前的范式被无动物的“下一代风险评估”（NGRA）取代。
