EVALUATIONS OF GENETIC TOXICITY TEST RESULTS

遗传毒性试验结果评价

• 批准号: 3841000
• 负责人: E ZEIGER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3841000
• 关键词: Salmonella; carcinogen testing; chemical carcinogen; chemical carcinogenesis; chemical information system; chemical structure function; computers; mutagen testing; mutagens; statistics /biometry; toxicant screening

A database of NTP short-term genetic toxicity test results and the results from carcinogenesis tests has been created. This database allows the evaluation of each short-term assay with respect to its ability to predict carcinogenesis or other short-term assay results. It also permits studies of the individual assays with respect to inter- and intra-laboratory reproducibility. Examination of test predictivity as a function of the potency of the short-term test (STT) and carcinogenicity test is continuing. The chemicals being evaluated comprise the 114-chemical dataset used previously to correlate qualitative STT results with carcinogenicity results. The short-term genetic toxicity results are being integrated with other toxicity and biochemical parameters of these chemicals in an attempt to improve the prediction of carcinogenicity and other toxic effects. A number of potency measures have been proposed for the Salmonella and carcinogenesis tests, but there are no commonly-accepted measures of potency for the other STTs, such as in vitro chromosome aberrations, in vitro SCE, or the mouse lymphoma test. The analyses of the potency measures for Salmonella are being redefined to fit the data from the mammalian cell assays, and will be used to evaluate the relationships of the in vivo tests with the carcinogenic potencies for the same chemicals. The database of Salmonella results was used to evaluate the ability of a number of procedures to predict mutagenicity. The predictivities for Salmonella mutagenicity of two computer-based structure- activity (SAR) systems, one empirical structure-activity system, and one physicochemical system, were determined for 100 chemicals. The chemical structures, or coded chemicals, were sent, without identifying them by name, to the participants. The study was designed to: measure the accuracy of the different test systems; identify the strengths and weaknesses of each system; and bring greater understanding to structure- activity predictions. The two computer-based SAR systems and empirical system gave equivalent predictivities (approx. 70-80%), while the physicochemical system was less effective (approx. 60%).

NTP短期遗传毒性试验结果数据库和结果 致癌试验的结果 该数据库允许 评价每种短期检测试剂盒的预测能力 致癌作用或其他短期测定结果。 它还允许研究 关于实验室间和实验室内 再现性 检验的预测性作为 短期试验（STT）和致癌性试验的效力是 继续。 正在评估的化学品包括114种化学品 先前用于将定性STT结果与 致癌性结果。 短期遗传毒性结果正在 与其他毒性和生化参数相结合， 化学品，试图改善致癌性的预测， 其他毒性作用。 已经提出了一些效力措施， 沙门氏菌和致癌性测试，但没有普遍接受的 其他STT的效力指标，如体外染色体 畸变、体外SCE或小鼠淋巴瘤试验。 的分析 沙门氏菌的效力措施正在重新定义，以适应来自 哺乳动物细胞分析，并将用于评估关系 体内试验的致癌效力相同 化学品 沙门氏菌结果数据库用于评估 许多程序预测致突变性的能力。 的 沙门氏菌致突变性的预测两个基于计算机的结构- 活性（SAR）系统，一个经验结构活性系统，一个 物理化学系统，测定了100种化学品。 化学 结构，或编码的化学品，被发送，没有识别他们， 姓名，参加者。 该研究旨在：测量 不同测试系统的准确性;确定优势， 每个系统的弱点;并加深对结构的理解- 活动预测。 这两个基于计算机的SAR系统和经验 系统给出了等效的预测性（近似值）。70-80%），而 物理化学系统的效率较低（约60%）。