Mielke H, Strickland J, Jacobs M N, Mehta J M
German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Str. 8-10, D-10589 Berlin, Germany.
ILS, Research Triangle Park, NC 27709, USA.
Regul Toxicol Pharmacol. 2017 Oct;89:26-39. doi: 10.1016/j.yrtph.2017.07.007. Epub 2017 Jul 11.
A comprehensive biometrical assessment was conducted to compare the performance of multiple test designs for acute dermal systemic toxicity to support the animal welfare update to the original OECD Test Guideline (TG) 402 for acute dermal toxicity. The test designs evaluated included: (1) two, three, or five animals per dose group (2) evident toxicity or lethality endpoints and (3) absence or presence of a one-animal sighting study. The revision of TG 402 respected the 3R principles (replace, reduce, refine) of animal testing. The results demonstrate that the TG 402 test design can be optimised with reduced animal numbers per test group, such that a scenario of two animals per group following a sighting study at a starting dose of 200 mg/kg bw (unless further information is available to better define the starting dose) would provide a classification which in most cases is conservative, without compromising both the statistical ability of the study to assess dermal toxicity, or the relevant classification outcome.
进行了全面的生物统计学评估，以比较多种急性经皮全身毒性试验设计的性能，以支持对经合组织（OECD）急性经皮毒性原始试验指南（TG）402进行动物福利更新。评估的试验设计包括：（1）每个剂量组2只、3只或5只动物；（2）明显的毒性或致死终点；（3）是否进行单只动物预试验。TG 402的修订遵循了动物试验的3R原则（替代、减少、优化）。结果表明，TG 402试验设计可以通过减少每个试验组的动物数量进行优化，即按照起始剂量200mg/kg体重进行预试验后每组2只动物的方案（除非有更多信息可更好地确定起始剂量），在大多数情况下可提供保守的分类，同时不会损害研究评估经皮毒性的统计能力或相关分类结果。
