Kramer Nynke I, Hermens Joop L M, Schirmer Kristin
Institute for Risk Assessment Sciences, Utrecht University, P.O. Box 80177, 3508 TD Utrecht, The Netherlands.
Toxicol In Vitro. 2009 Oct;23(7):1372-9. doi: 10.1016/j.tiv.2009.07.029. Epub 2009 Aug 3.
New EU legislation is providing an impetus for research aimed at replacing acute fish toxicity testing with in vitro alternatives. In line with such research, the objective of this study was to determine what factors influence the correlation between in vitro and fish toxicity data. Basal cytotoxicity (IC(50)) and acute toxicity data from fathead minnow (LC(50)) of 82 industrial organic chemicals were obtained from the Halle Registry of Cytotoxicity and the US EPA Fathead Minnow Database. A good correlation between IC(50) with LC(50) data was found (r 0.84). Yet, IC(50) data were less sensitive than LC(50) data by an order of magnitude. Using multiple regression analysis, the octanol-water partition coefficient (K(OW)) and the Henry's Law Constant (H) were found to significantly explain the low absolute sensitivity. The mode of action (MOA) of the chemical was found to significantly explain the general variation in the logIC(50)/log LC(50) regression line. These results support the notion that (a) the bioavailability of hydrophobic (high K(OW)) and volatile (high H) chemicals is significantly lower in in vitro assays than in the fish bioassay and (b) multiple cell types and endpoints should be included to mimic the modes of action possible in the whole organism.
欧盟新法规正在推动旨在用体外替代方法取代急性鱼类毒性试验的研究。与此类研究一致，本研究的目的是确定哪些因素会影响体外试验与鱼类毒性数据之间的相关性。从哈雷细胞毒性登记处和美国环保署黑头呆鱼数据库获取了82种工业有机化学品的基础细胞毒性（IC(50)）和黑头呆鱼的急性毒性数据（LC(50)）。发现IC(50)与LC(50)数据之间存在良好的相关性（r = 0.84）。然而，IC(50)数据的敏感性比LC(数据低一个数量级。通过多元回归分析，发现正辛醇-水分配系数（K(OW)）和亨利定律常数（H）能显著解释这种较低的绝对敏感性。发现化学品的作用模式（MOA）能显著解释logIC(50)/log LC(50)回归线的总体变化。这些结果支持以下观点：(a) 在体外试验中，疏水性（高K(OW)）和挥发性（高H）化学品的生物利用度明显低于鱼类生物试验；(b) 应纳入多种细胞类型和终点指标，以模拟整个生物体中可能的作用模式。
