Buzzi R, Würgler F E
Comparative Physiology Laboratory, Swiss Federal Institute of Technology, Zurich.
Mutat Res. 1990 Oct;234(5):269-88. doi: 10.1016/0165-1161(90)90039-q.
A construction of batteries of short-term tests (STTs) is described which is based on a classification of 73 chemicals in regard to their carcinogenicity. The 73 chemicals were studied within the U.S. National Toxicology Program (Ashby and Tennant, 1988). The batteries are validated using the classification of 35 additional chemicals. They are defined by logically structured combinations of rules. The single rules are defined by the z-scores of the logarithmic values of the limiting doses obtained from the 4 in vitro STTs used in the study by Ashby and Tennant. The limiting dose is defined as the lowest effective dose or the highest ineffective dose (Waters et al., 1987). The batteries are constructed by minimizing the number of disagreements with the classification by Ashby and Tennant. Compared with the results obtained from single STTs, 2 batteries of 3 STTs have higher concordances with the carcinogenicity data, namely 70% for the NTP data and 74-77% for the independent test data. In addition, a theoretical result shows that the proposed battery design, for a large enough learning set of chemicals, leads to results which are replicated with high probability on a large enough validation set. Based on the first results obtained with a limited number of chemicals it is concluded that the knowledge-based battery design is worth further development.
本文描述了一种基于73种化学物质致癌性分类构建的短期试验（STT）组合。这73种化学物质是在美国国家毒理学计划中进行研究的（阿什比和坦南特，1988年）。这些试验组合通过另外35种化学物质的分类进行验证。它们由逻辑结构的规则组合定义。单个规则由从阿什比和坦南特研究中使用的4种体外短期试验获得的极限剂量对数值的z分数定义。极限剂量定义为最低有效剂量或最高无效剂量（沃特斯等人，1987年）。这些试验组合的构建是通过尽量减少与阿什比和坦南特分类的分歧数量来实现的。与单个短期试验结果相比，两个由3个短期试验组成的试验组合与致癌性数据的一致性更高，即对于美国国家毒理学计划数据为70%，对于独立试验数据为74 - 77%。此外，一个理论结果表明，对于足够大的化学物质学习集，所提出的试验组合设计在足够大的验证集上产生的结果很可能被复制。基于对有限数量化学物质获得的初步结果，可以得出结论，基于知识的试验组合设计值得进一步开发。
