Huggins Jane
Toxicology Consulting Services, Plainsboro, USA.
ALTEX. 2003;20(Suppl 1):3-61.
Current trends and issues in the development of alternatives to the use of animals in biomedical experimentation are discussed in this position paper. Eight topics are considered and include refinement of acute toxicity assays; eye corrosion/irritation alternatives; skin corrosion/irritation alternatives; contact sensitization alternatives; developmental/reproductive testing alternatives; genetic engineering (transgenic) assays; toxicogenomics; and validation of alternative methods. The discussion of refinement of acute toxicity assays is focused primarily on developments with regard to reduction of the number of animals used in the LD(50) assay. However, the substitution of humane endpoints such as clinical signs of toxicity for lethality in these assays is also evaluated. Alternative assays for eye corrosion/irritation as well as those for skin corrosion/irritation are described with particular attention paid to the outcomes, both successful and unsuccessful, of several validation efforts. Alternative assays for contact sensitization and developmental/reproductive toxicity are presented as examples of methods designed for the examination of interactions between toxins and somewhat more complex physiological systems. Moreover, genetic engineering and toxicogenomics are discussed with an eye toward the future of biological experimentation in general. The implications of gene manipulation for research animals, specifically, are also examined. Finally, validation methods are investigated as to their effectiveness, or lack thereof, and suggestions for their standardization and improvement, as well as implementation are reviewed.
本立场文件讨论了生物医学实验中动物使用替代方法发展的当前趋势和问题。共考虑了八个主题，包括急性毒性试验的优化；眼腐蚀/刺激替代方法；皮肤腐蚀/刺激替代方法；接触致敏替代方法；发育/生殖毒性试验替代方法；基因工程（转基因）试验；毒理基因组学；以及替代方法的验证。急性毒性试验优化的讨论主要集中在减少半数致死量（LD50）试验中所用动物数量方面的进展。不过，也评估了在这些试验中用人道终点（如毒性临床体征）替代致死性的情况。描述了眼腐蚀/刺激以及皮肤腐蚀/刺激的替代试验，并特别关注了几次验证工作的成功与失败结果。接触致敏和发育/生殖毒性的替代试验作为旨在检测毒素与更复杂生理系统之间相互作用的方法示例进行了介绍。此外，还从总体上展望生物实验未来的角度讨论了基因工程和毒理基因组学。具体而言，还研究了基因操作对实验动物的影响。最后，考察了验证方法的有效性或无效性，并审视了其标准化、改进及实施方面的建议。
