National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), UK.
Board Member, NC3Rs, UK.
Regul Toxicol Pharmacol. 2018 Apr;94:22-32. doi: 10.1016/j.yrtph.2018.01.001. Epub 2018 Jan 6.
Acute inhalation studies are conducted in animals as part of chemical hazard identification and for classification and labelling. Current methods employ death as an endpoint (Organisation for Economic Co-operation and Development (OECD) test guideline (TG) 403 and TG436) while the recently approved fixed concentration procedure (FCP) (OECD TG433) uses fewer animals and replaces lethality as an endpoint with evident toxicity. Evident toxicity is the presence of clinical signs that predict that exposure to the next highest concentration will cause severe toxicity or death in most animals. Approval of TG433 was the result of an international initiative, led by the National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), which collected data from six laboratories on clinical signs recorded for inhalation studies on 172 substances. This paper summarises previously published data and describes the additional analyses of the dataset that were essential for approval of the TG.
急性吸入研究在动物体内进行，作为化学危害识别以及分类和标签的一部分。目前的方法采用死亡作为终点（经济合作与发展组织（OECD）测试指南（TG）403 和 TG436），而最近批准的固定浓度程序（FCP）（OECD TG433）使用较少的动物，并将致死性作为终点替换为明显的毒性。明显的毒性是指存在临床症状，这些症状表明，暴露于下一个更高浓度将导致大多数动物出现严重毒性或死亡。TG433 的批准是由国家替代、改良和减少研究动物中心（NC3Rs）领导的国际倡议的结果，该倡议从六个实验室收集了 172 种物质吸入研究中记录的临床症状数据。本文总结了之前发表的数据，并描述了对数据集进行的额外分析，这些分析对于 TG 的批准是必不可少的。
