Kennah H E, Albulescu D, Hignet S, Barrow C S
Department of Toxicology, PPG Industries, Inc., Pittsburgh, Pennsylvania 15238.
Fundam Appl Toxicol. 1989 Feb;12(2):281-90. doi: 10.1016/0272-0590(89)90045-6.
Numerous in vitro cytotoxicity assays have been proposed as potential alternatives to the Draize eye irritancy test. The results reported, based upon the rank correlation of ocular irritancy with cytotoxicity, have been encouraging. However, direct calibration of in vivo to in vitro data utilizing several categories of chemicals has not been reported. This study evaluated the use of in vitro cytotoxicity data for predicting the ocular irritancy potential of 24 chemicals (six surfactants, seven alcohols, four ketones, four acetates, and three aromatics). BALB/c 3T3 cells were grown overnight, then exposed for 30 min to at least four different concentrations of each chemical (expressed as volume percentage). Linear regression analysis of the log concentration versus percentage of control growth was used to calculate the concentration of toxicant that inhibited the normal growth rate by 50% (GI50). The rank ordering of cytotoxicity based upon the GI50s was surfactants greater than aromatics greater than alcohols greater than ketones or acetates. The larger molecular weight representative of each series (i.e., 2-ethyl-1-hexanol for alcohols) had lower GI50 values than those of the lower molecular weight substances. The GI50 values were then directly calibrated against in vivo ocular irritancy quantitated as percentage corneal swelling following exposure of rabbits to the same test chemicals. A significant linear correlation between cytotoxicity and ocular irritancy was established only for surfactants and alcohols. For acetates, ketones, and aromatics there was little correlation. The overall poor correlation between cytotoxicity and ocular irritancy was attributed to differences in mechanisms of irritancy. The lack of correlation illustrates that in vitro cytotoxicity data cannot be used to predict the ocular irritancy potential of a broad spectrum of chemicals.
已经提出了许多体外细胞毒性试验，作为Draize眼刺激试验的潜在替代方法。根据眼刺激与细胞毒性的等级相关性报告的结果令人鼓舞。然而，尚未有利用几类化学物质对体内和体外数据进行直接校准的报道。本研究评估了体外细胞毒性数据用于预测24种化学物质（6种表面活性剂、7种醇类、4种酮类、4种醋酸酯类和3种芳烃类）眼刺激潜力的情况。将BALB/c 3T3细胞培养过夜，然后将其暴露于每种化学物质的至少四种不同浓度（以体积百分比表示）下30分钟。使用对数浓度与对照生长百分比的线性回归分析来计算抑制正常生长率50%的毒物浓度（GI50）。基于GI50的细胞毒性等级顺序为：表面活性剂＞芳烃＞醇类＞酮类或醋酸酯类。每个系列中分子量较大的代表性物质（即醇类中的2-乙基-1-己醇）的GI50值低于分子量较小的物质。然后将GI50值与体内眼刺激进行直接校准，体内眼刺激以兔暴露于相同测试化学物质后角膜肿胀的百分比来定量。仅在表面活性剂和醇类中建立了细胞毒性与眼刺激之间的显著线性相关性。对于醋酸酯类、酮类和芳烃类，相关性很小。细胞毒性与眼刺激之间总体相关性较差归因于刺激机制的差异。缺乏相关性表明体外细胞毒性数据不能用于预测广泛化学物质的眼刺激潜力。
