School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, United Kingdom.
Reprod Toxicol. 2010 Aug;30(1):147-60. doi: 10.1016/j.reprotox.2009.12.003. Epub 2009 Dec 16.
It has been estimated that reproductive and developmental toxicity tests will account for a significant proportion of the testing costs associated with REACH compliance. Consequently, the use of alternative methods to predict developmental toxicity is an attractive prospect. The present study evaluates a number of computational models and tools which can be used to aid assessment of developmental toxicity potential. The performance and limitations of traditional (quantitative) structure-activity relationship ((Q)SARs) modelling, structural alert-based expert system prediction and chemical profiling approaches are discussed. In addition, the use of category formation and read-across is also addressed. This study demonstrates the limited success of current modelling methods when used in isolation. However, the study also indicates that when used in combination, in a weight-of-evidence approach, better use may be made of the limited toxicity data available and predictivity improved. Recommendations are provided as to how this area could be further developed in the future.
据估计，生殖和发育毒性测试将占与 REACH 合规相关的测试成本的很大一部分。因此，使用替代方法来预测发育毒性是一个有吸引力的前景。本研究评估了一些计算模型和工具，这些模型和工具可用于辅助评估发育毒性潜力。讨论了传统（定量）构效关系（QSAR）建模、基于结构警报的专家系统预测和化学特征分析方法的性能和局限性。此外，还讨论了类别形成和读通的使用。本研究表明，当前的建模方法在单独使用时的成功率有限。然而，该研究还表明，当以综合证据的方法使用时，可以更好地利用现有的有限毒性数据，并提高预测能力。提供了有关如何在未来进一步发展这一领域的建议。
