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Abstract：
Genotoxicity testing for nanomaterials remains challenging as standard testing approaches require some adaptation, and further development of nano-specific OECD Test Guidelines (TGs) and Guidance Documents (GDs) are needed. However, the field of genotoxicology continues to progress and new approach methodologies (NAMs) are being developed that could provide relevant information on the range of mechanisms of genotoxic action that may be imparted by nanomaterials. There is a recognition of the need for implementation of new and/or adapted OECD TGs, new OECD GDs, and utilization of NAMs within a genotoxicity testing framework for nanomaterials. As such, the requirements to apply new experimental approaches and data for genotoxicity assessment of nanomaterials in a regulatory context is neither clear, nor used in practice. Thus, an international workshop with representatives from regulatory agencies, industry, government, and academic scientists was convened to discuss these issues. The expert discussion highlighted the current deficiencies that exist in standard testing approaches within exposure regimes, insufficient physicochemical characterization, lack of demonstration of cell or tissue uptake and internalization, and limitations in the coverage of genotoxic modes of action. Regarding the latter aspect, a consensus was reached on the importance of using NAMs to support the genotoxicity assessment of nanomaterials. Also highlighted was the need for close engagement between scientists and regulators to (i) provide clarity on the regulatory needs, (ii) improve the acceptance and use of NAM-generated data, and (iii) define how NAMs may be used as part of weight of evidence approaches for use in regulatory risk assessments.
摘要：
纳米材料的遗传毒性测试仍然具有挑战性，因为标准测试方法需要一些适应，需要进一步开发特定于纳米的OECD测试指南（TG）和指导文件（GD）。然而,基因毒理学领域继续取得进展,并且正在开发新的方法方法(NAMs),这些方法可以提供有关纳米材料可能赋予的基因毒性作用机制的相关信息.人们认识到有必要实施新的和/或经过调整的经合组织TG，新的OECDGDs和纳米材料遗传毒性测试框架内NAM的利用。因此，在监管背景下应用新的实验方法和数据进行纳米材料遗传毒性评估的要求并不明确，也没有在实践中使用。因此，由监管机构代表参加的国际研讨会，工业,政府,和学术科学家被召集来讨论这些问题。专家讨论强调了暴露制度内标准测试方法目前存在的缺陷，物理化学表征不足，缺乏细胞或组织摄取和内化的证明，以及基因毒性作用模式覆盖范围的局限性。关于后一方面，就使用NAMs支持纳米材料遗传毒性评估的重要性达成共识.还强调了科学家和监管机构之间需要密切接触，以1)明确监管需求，2）提高NAM生成数据的接受和使用，and3)definehowNAMsmaybeusedaspartofWeightofEvidenceapproachesforuseinregulatoryriskassessments.
