Harbell J W, Koontz S W, Lewis R W, Lovell D, Acosta D
Microbiological Associates, Inc., Rockville, MD 20850, USA.
Food Chem Toxicol. 1997 Jan;35(1):79-126. doi: 10.1016/s0278-6915(96)00101-9.
Twenty-seven data sets from 12 cellular cytotoxicity assays, intended to predict ocular irritation, were submitted to the Interagency Regulatory Alternatives Group (IRAG) for review. These data consisted of paired in vivo (Draize) and in vitro responses to individual chemicals and formulations. In vivo data consisted of individual tissue scores so that the predictive value of the in vitro assay could be assessed for each tissue response normally measured in the standard Draize assay. Data were compiled and evaluated according to the IRAG Guidelines Document. The Pearson's linear correlation coefficient was used as the first step in assessing the relationship between the in vitro and in vivo responses. The majority of the data sets represented the study of surfactant-based materials. In many cases, there was good correlation between the in vitro scores and the in vivo tissue responses. Most pronounced were the particularly good correlations between the in vitro scores and conjunctival redness scores across most of the assays. Based on the data submitted, a number of the cell cytotoxicity assays show considerable promise as screens for ocular irritancy. None of the submitters recommended that their cell cytotoxicity assay be used as a sole replacement for in vivo assessment. For almost all of these assays, the materials being tested should be water-soluble/miscible. The toxicity of products with reserve acidity or alkalinity or with high reactivity may be underestimated. A given user may prefer certain assays depending on the types of materials to be tested, the expected range of toxicities and the resources available. The cell cytotoxicity assays can serve as a valuable component of a tiered or battery testing program. As with any assay, a sufficient number of replicate values, concurrent positive and negative controls, and a strict adherence to assay acceptance criteria are essential to produce credible data.
来自12项细胞毒性试验的27个数据集,旨在预测眼刺激性,已提交给跨部门监管替代方法小组(IRAG)进行审查。这些数据包括对单个化学品和配方的体内(Draize)和体外反应的配对数据。体内数据由个体组织评分组成,以便可以针对标准Draize试验中通常测量的每个组织反应评估体外试验的预测价值。数据根据IRAG指南文件进行汇编和评估。皮尔逊线性相关系数被用作评估体外和体内反应之间关系的第一步。大多数数据集代表了基于表面活性剂材料的研究。在许多情况下,体外评分与体内组织反应之间存在良好的相关性。最明显的是,在大多数试验中,体外评分与结膜充血评分之间的相关性特别好。基于提交的数据,一些细胞毒性试验作为眼刺激性筛选显示出相当大的前景。没有提交者建议将其细胞毒性试验用作体内评估的唯一替代方法。对于几乎所有这些试验,所测试的材料应是水溶性/混溶性的。具有储备酸度或碱度或高反应性的产品的毒性可能被低估。特定用户可能会根据要测试的材料类型、预期的毒性范围和可用资源选择某些试验。细胞毒性试验可以作为分层或系列测试计划的一个有价值的组成部分。与任何试验一样,足够数量的重复值、同时的阳性和阴性对照以及严格遵守试验接受标准对于产生可靠的数据至关重要。