Gettings S D, Dipasquale L C, Bagley D M, Casterton P L, Chudkowski M, Curren R D, Demetrulias J L, Feder P I, Galli C L, Gay R
Cosmetic, Toiletry and Fragrance Association, Washington, DC 20036.
Food Chem Toxicol. 1994 Oct;32(10):943-76. doi: 10.1016/0278-6915(94)90092-2.
The Cosmetic, Toiletry and Fragrance Association (CTFA) Evaluation of Alternatives Program is an evaluation of the relationship between Draize ocular safety test data and comparable data from a selection of in vitro tests. In Phase II, 18 representative oil/water-based personal-care formulations were subjected to the Draize primary eye safety test and 30 in vitro assay protocols (14 different types of in vitro endpoints were evaluated; the remainder were protocol variations). Correlation of in vitro with in vivo data was evaluated using analysis of sensitivity/specificity and statistical analysis of the relationship between maximum average Draize score (MAS) and in vitro endpoint. Regression modelling is the primary approach adopted in the CTFA Program for evaluating in vitro assay performance. The objective of regression analysis is to predict MAS for a given test material (and to place upper and lower prediction interval bounds on the range in which the MAS is anticipated to fall with high probability) conditional on observing an in vitro assay score for that material. The degree of confidence in prediction is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curves: the narrower the prediction interval, the more predictive of the Draize score is the in vitro test result. 16 assays were shown to have the greatest agreement with the Draize procedure and were therefore selected for regression analysis. Based on the magnitude of the 95% prediction bounds of each of the 16 selected assays over the range of test data, it may be inferred that prediction of MAS values from experimentally determined in vitro scores is more accurate for oil/water-based formulations with lower rather than higher irritancy potential. The assays selected for modelling in Phase II generally exhibited weaker relationships with MAS than those selected in Phase I (evaluated using hydroalcoholic formulations), even though several assays were common to both Phases.
化妆品、盥洗用品和香料协会（CTFA）替代方法评估项目是对德莱兹眼安全测试数据与一系列体外测试的可比数据之间的关系进行评估。在第二阶段，18种代表性油/水基个人护理配方产品接受了德莱兹主要眼安全测试以及30种体外检测方案（评估了14种不同类型的体外终点；其余为方案变体）。使用敏感性/特异性分析以及最大平均德莱兹评分（MAS）与体外终点之间关系的统计分析来评估体外数据与体内数据的相关性。回归建模是CTFA项目中用于评估体外检测性能的主要方法。回归分析的目的是在观察到某测试材料的体外检测分数的条件下，预测该测试材料的MAS（并给出MAS预计大概率会落入的范围的上下预测区间界限）。预测的置信度通过围绕拟合回归曲线构建的预测区间的相对宽度来量化：预测区间越窄，体外测试结果对德莱兹评分的预测性就越强。16种检测方法显示与德莱兹程序的一致性最高，因此被选用于回归分析。根据16种选定检测方法在测试数据范围内的95%预测界限的大小，可以推断，对于刺激性潜力较低而非较高的油/水基配方产品，根据实验确定的体外分数预测MAS值更为准确。尽管两个阶段有几种检测方法是相同的，但第二阶段选入建模的检测方法与MAS的关系通常比第一阶段（使用水醇配方产品进行评估）选入的检测方法更弱。
