DABMEB Consultancy, Sharnbrook, UK.
ALTEX. 2012;29(1):3-91. doi: 10.14573/altex.2012.1.003.
Systemic toxicity testing forms the cornerstone for the safety evaluation of substances. Pressures to move from traditional animal models to novel technologies arise from various concerns, including: the need to evaluate large numbers of previously untested chemicals and new products (such as nanoparticles or cell therapies), the limited predictivity of traditional tests for human health effects, duration and costs of current approaches, and animal welfare considerations. The latter holds especially true in the context of the scheduled 2013 marketing ban on cosmetic ingredients tested for systemic toxicity. Based on a major analysis of the status of alternative methods (Adler et al., 2011) and its independent review (Hartung et al., 2011), the present report proposes a roadmap for how to overcome the acknowledged scientific gaps for the full replacement of systemic toxicity testing using animals. Five whitepapers were commissioned addressing toxicokinetics, skin sensitization, repeated-dose toxicity, carcinogenicity, and reproductive toxicity testing. An expert workshop of 35 participants from Europe and the US discussed and refined these whitepapers, which were subsequently compiled to form the present report. By prioritizing the many options to move the field forward, the expert group hopes to advance regulatory science.
系统毒性测试是物质安全性评价的基石。出于各种考虑，人们希望从传统动物模型转向新型技术，这些考虑因素包括：需要评估大量以前未经测试的化学品和新产品（如纳米颗粒或细胞疗法）；传统测试对人类健康影响的预测性有限；当前方法的持续时间和成本；以及动物福利方面的考虑。在后一种情况下，2013 年计划对用于系统毒性测试的化妆品成分进行营销禁令的背景尤其如此。本报告基于对替代方法现状的主要分析（Adler 等人，2011 年）及其独立审查（Hartung 等人，2011 年），提出了如何克服公认的科学差距，全面用动物替代系统毒性测试的路线图。本报告委托编写了五份关于毒代动力学、皮肤致敏、重复剂量毒性、致癌性和生殖毒性测试的白皮书。来自欧洲和美国的 35 名专家参加了一个专家研讨会，讨论并完善了这些白皮书，随后将其汇编成本报告。专家组通过优先考虑推进该领域的许多选择，希望推动监管科学的发展。
