Gettings S D, Lordo R A, Feder P I, Hintze K L
The Cosmetic, Toiletry and Fragrance Association, Washington, DC 20036, USA.
Food Chem Toxicol. 1998 Mar;36(3):209-31. doi: 10.1016/s0278-6915(97)00135-x.
The third phase in a series of investigations of the relationship between low volume eye test (LVET) data, Draize eye irritation test data, and comparable data from in vitro assay protocols is presented. These investigations utilize Draize eye test and in vitro endpoint data generated previously as part of the CTFA Evaluation of Alternatives Program. LVET data were generated de novo using the same 25 representative surfactant-based personal-care formulations. In general, these formulations were minimally to moderately irritating. The linear correlation between maximum average score as determined by the Draize test (MAS) and the LVET (LVET-MAS) was 0.87; LVET-MAS values were typically about 30% lower then corresponding MAS values. Comparison of in vitro assay performance with that of the LVET was determined by statistical analysis of the relationship between LVET-MAS and in vitro endpoint. Regression modelling was the primary means of enabling such a comparison, the objective being to predict LVET-MAS for a given test material (and to place upper and lower prediction bounds on the range in which the LVET-MAS is anticipated to fall with high probability) based on observation of an in vitro score for that material. The degree of 95% confidence in prediction is quantified in terms of the relative widths of prediction intervals constructed about the fitted regression curves. Twenty in vitro endpoints were shown to have the greatest agreement with the LVET (these endpoints included those with low discordance rates relative to the Draize test) and were therefore selected for regression modelling. Although prediction interval widths tended to be narrower when predicting LVET-MAS compared with predicting MAS, the confidence with which the selected in vitro endpoints predicted both LVET-MAS and MAS for surfactant-based formulations was greatest when values were close to the lower or upper limits of the observed irritation range (i.e. 95% prediction interval widths were most narrow in these areas). Overall precision of LVET-MAS prediction for surfactant-based formulations was similar to that previously reported for hydroalcoholic formulations and considerably better than was reported for oil/water emulsions.
本文介绍了一系列关于低容量眼测试（LVET）数据、德雷兹眼刺激试验数据以及来自体外试验方案的可比数据之间关系研究的第三阶段。这些研究利用了先前作为CTFA替代方案评估项目一部分生成的德雷兹眼测试和体外终点数据。LVET数据是使用相同的25种代表性表面活性剂基个人护理配方重新生成的。总体而言，这些配方的刺激性为轻度至中度。德雷兹试验确定的最大平均得分（MAS）与LVET（LVET-MAS）之间的线性相关性为0.87；LVET-MAS值通常比相应的MAS值低约30%。通过对LVET-MAS与体外终点之间关系的统计分析，确定了体外试验性能与LVET的比较。回归建模是进行这种比较的主要手段，目标是根据对某一材料的体外得分观察，预测给定测试材料的LVET-MAS（并为LVET-MAS预计很可能落入的范围设定上下预测界限）。预测的95%置信度根据围绕拟合回归曲线构建的预测区间的相对宽度进行量化。20个体外终点显示与LVET的一致性最高（这些终点包括相对于德雷兹试验不一致率较低的终点），因此被选用于回归建模。尽管与预测MAS相比，预测LVET-MAS时预测区间宽度往往更窄，但当值接近观察到的刺激范围的下限或上限时（即这些区域的95%预测区间宽度最窄），所选体外终点预测基于表面活性剂配方的LVET-MAS和MAS的置信度最高。基于表面活性剂配方的LVET-MAS预测的总体精度与先前报道的含醇配方相似，且远优于油/水乳液的报道精度。
