New supporting data to guide the use of evident toxicity in acute oral toxicity studies (OECD TG 420)

Fiona Sewell, Ian Ragan,Graham Horgan, David Andrew,Thomas Holmes, Irene Manou,Boris P. Mueller, Tim Rowan, Barbara G. Schmitt,Marco Corvaro

REGULATORY TOXICOLOGY AND PHARMACOLOGY(2024)

引用 0|浏览2
暂无评分
摘要
Currently there are three test guidelines (TG) for acute oral toxicity studies of substances or mixtures from the Organisation for Economic Co-operation and Development (OECD). TG 423 and TG 425 use lethality as an endpoint, while TG 420 replaces death with 'evident toxicity', defined as clear signs that exposure to a higher dose would result in death. However, the perceived subjectivity of 'evident toxicity' may be preventing wider use of TG 420. To address this, the UK National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) and the European Partnership for Alternative Approaches to Animal Testing (EPAA) collaborated to provide recommendations on the recognition of 'evident toxicity'. Historical data from acute oral toxicity studies were analysed for clinical signs at the lower dose that could have predicted death at the higher dose. Several signs including ataxia, laboured respiration, and eyes partially closed, alone or in combination, are highly predictive. Others such as lethargy, decreased respiration, and loose faeces have lower but still appreciable positive predictive value (PPV). The data has been used to develop recommendations to promote use of TG 420 and thus reduce the suffering and numbers of animals used in acute oral toxicity studies.
更多
查看译文
关键词
Acute oral toxicity studies,3Rs,Evident toxicity,Fixed dose procedure (FDP),Refinement,Regulatory toxicology,OECD TG 420
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要