Boverhof Darrell R, Ladics Greg, Luebke Bob, Botham Jane, Corsini Emanuela, Evans Ellen, Germolec Dori, Holsapple Michael, Loveless Scott E, Lu Haitian, van der Laan Jan Willem, White Kimber L, Yang Yung
The Dow Chemical Company, Midland, MI, United States.
DuPont Pioneer, Wilmington, DE, United States.
Regul Toxicol Pharmacol. 2014 Feb;68(1):96-107. doi: 10.1016/j.yrtph.2013.11.012. Epub 2013 Nov 23.
As experience is gained with toxicology testing and as new assays and technologies are developed, it is critical for stakeholders to discuss opportunities to advance our overall testing strategies. To facilitate these discussions, a workshop on practices for assessing immunotoxicity for environmental chemicals was held with the goal of sharing perspectives on immunotoxicity testing strategies and experiences, developmental immunotoxicity (DIT), and integrated and alternative approaches to immunotoxicity testing. Experiences across the chemical and pharmaceutical industries suggested that standard toxicity studies, combined with triggered-based testing approaches, represent an effective and efficient approach to evaluate immunotoxic potential. Additionally, discussions on study design, critical windows, and new guideline approaches and experiences identified important factors to consider before initiating DIT evaluations including assay choice and timing and the impact of existing adult data. Participants agreed that integrating endpoints into standard repeat-dose studies should be considered for fulfilling any immunotoxicity testing requirements, while also maximizing information and reducing animal use. Participants also acknowledged that in vitro evaluation of immunosuppression is complex and may require the use of multiple assays that are still being developed. These workshop discussions should contribute to developing an effective but more resource and animal efficient approach for evaluating chemical immunotoxicity.
随着毒理学测试经验的积累以及新检测方法和技术的发展,利益相关者讨论推进我们整体测试策略的机会至关重要。为促进这些讨论,举办了一次关于评估环境化学品免疫毒性实践的研讨会,目的是分享关于免疫毒性测试策略和经验、发育免疫毒性(DIT)以及免疫毒性测试的综合和替代方法的观点。化学和制药行业的经验表明,标准毒性研究与基于触发的测试方法相结合,是评估免疫毒性潜力的有效且高效的方法。此外,关于研究设计、关键窗口期以及新指南方法和经验的讨论确定了在启动DIT评估之前需要考虑的重要因素,包括检测方法的选择和时间安排以及现有成年动物数据的影响。参与者一致认为,为满足任何免疫毒性测试要求,应考虑将终点指标纳入标准重复剂量研究,同时还要最大限度地获取信息并减少动物使用。参与者还承认,免疫抑制的体外评估很复杂,可能需要使用多种仍在开发中的检测方法。这些研讨会讨论应有助于制定一种有效但更节省资源和动物的方法来评估化学物质的免疫毒性。