National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), Gibbs Building, 215 Euston Road, London, NW1 2BE, UK.
Syngenta Ltd., Jealott's Hill International Research Centre, Bracknell, Berkshire, UK.
Regul Toxicol Pharmacol. 2021 Dec;127:105068. doi: 10.1016/j.yrtph.2021.105068. Epub 2021 Oct 19.
Agrochemical safety assessment has traditionally relied on the use of animals for toxicity testing, based on scientific understanding and test guidelines developed in the 1980s. However, since then, there have been significant advances in the toxicological sciences that have improved our understanding of mechanisms underpinning adverse human health effects. The time is ripe to 'rethink' approaches used for human safety assessments of agrochemicals to ensure they reflect current scientific understanding and increasingly embrace new opportunities to improve human relevance and predictivity, and to reduce the reliance on animals. Although the ultimate aim is to enable a paradigm shift and an overhaul of global regulatory data requirements, there is much that can be done now to ensure new opportunities and approaches are adopted and implemented within the current regulatory frameworks. This commentary reviews current initiatives and emerging opportunities to embrace new approaches to improve agrochemical safety assessment for humans, and considers various endpoints and initiatives (including acute toxicity, repeat dose toxicity studies, carcinogenicity, developmental and reproductive toxicity, exposure-driven approaches, inhalation toxicity, and data modelling). Realistic aspirations to improve safety assessment, incorporate new technologies and reduce reliance on animal testing without compromising protection goals are discussed.
农药安全性评估传统上依赖于使用动物进行毒性测试，这是基于 20 世纪 80 年代发展起来的科学理解和测试指南。然而，自那时以来，毒理学科学取得了重大进展，加深了我们对不良人类健康影响的潜在机制的理解。现在是时候“重新思考”用于农药人类安全性评估的方法了，以确保它们反映当前的科学认识，并越来越多地利用新的机会来提高人类相关性和预测性，并减少对动物的依赖。虽然最终目标是实现范式转变和全面改革全球监管数据要求，但现在可以做很多工作来确保在当前监管框架内采用和实施新的机会和方法。本评论审查了当前的倡议和新兴机会，以采用新方法来改善人类的农药安全性评估，并考虑了各种终点和倡议（包括急性毒性、重复剂量毒性研究、致癌性、发育和生殖毒性、暴露驱动方法、吸入毒性和数据建模）。讨论了在不损害保护目标的情况下，提高安全性评估、采用新技术和减少对动物测试的依赖的现实愿望。
