Spielmann H, Balls M, Dupuis J, Pape W J, Pechovitch G, de Silva O, Holzhütter H G, Clothier R, Desolle P, Gerberick F, Liebsch M, Lovell W W, Maurer T, Pfannenbecker U, Potthast J M, Csato M, Sladowski D, Steiling W, Brantom P
ZEBET, BgVV, Berlin, Germany.
Toxicol In Vitro. 1998 Jun 1;12(3):305-27. doi: 10.1016/s0887-2333(98)00006-x.
To date, no standardized international guideline for the testing of chemicals for phototoxic potential has been accepted for regulatory purposes. In 1991, the European Commission (EC), represented initially by the Directorate General XI and later by ECVAM (the European Centre for the Validation of Alternative Methods) and COLIPA (the European Cosmetic, Toiletry and Perfumery Association), agreed to establish a joint EU/COLIPA programme on the development and validation of in vitro phototoxicity tests. The first phase (phase I, 1992-93) was designed as a prevalidation study, to identify in vitro test procedures and test protocols for a formal validation trial under blind conditions. In the second phase (phase II, 1994-95), the formal validation study, the most promising in vitro phototoxicity tests were validated with 30 carefully selected test chemicals in 11 laboratories in a blind trial. The 3T3 mouse fibroblast neutral red uptake phototoxicity test (3T3 NRU PT) was performed as a core test in nine laboratories, since it provided the best results in phase I of the study. The purpose of phase II was to confirm the reliability and relevance of the in vitro tests for predicting phototoxic effects and for identifying phototoxic chemicals. In phase II the phototoxic potential of test chemicals in the 3T3 NRU PT test was either assessed by determining the phototoxicity factor (PIF) by using a cut-off value of 5 as in phase I of the study, or by determining the mean photo effect (MPE) by using a cut-off value of 0.1, as recently proposed by Holzhütter (1997). Results obtained with both approaches in the 3T3 NRU PT test in phase II were reproducible in the nine laboratories, and the correlation between in vitro and in vivo data was very high. Therefore, ECVAM and COLIPA conclude from this formal validation trial under blind conditions that the 3T3 NRU PT test is a scientifically validated in vitro test which is ready to be considered for regulatory purposes for assessing the phototoxic potential of chemicals. A draft OECD Guideline for "In Vitro Phototoxicity Testing", incorporating the standard protocol of the 3T3 NRU PT test, will be submitted to the OECD test guidelines programme in due course.
迄今为止，尚未有用于化学品光毒性潜力测试的标准化国际准则被监管机构所接受。1991年，欧盟委员会（EC），最初由第十一总局代表，后来由欧洲替代方法验证中心（ECVAM）和欧洲化妆品、盥洗用品和香料协会（COLIPA）代表，同意设立一个关于体外光毒性测试开发和验证的欧盟/COLIPA联合项目。第一阶段（第一阶段，1992 - 93年）被设计为一项预验证研究，以确定用于盲法条件下正式验证试验的体外测试程序和试验方案。在第二阶段（第二阶段，1994 - 95年），即正式验证研究阶段，最有前景的体外光毒性测试在11个实验室中对30种精心挑选的测试化学品进行了盲法试验验证。3T3小鼠成纤维细胞中性红摄取光毒性试验（3T3 NRU PT）在9个实验室中作为核心试验进行，因为它在研究的第一阶段提供了最佳结果。第二阶段的目的是确认体外测试在预测光毒性效应和识别光毒性化学品方面的可靠性和相关性。在第二阶段，3T3 NRU PT试验中测试化学品的光毒性潜力要么像研究第一阶段那样通过使用5的临界值确定光毒性因子（PIF）来评估，要么像Holzhütter（1997年）最近提议的那样通过使用0.1的临界值确定平均光效应（MPE）来评估。在第二阶段3T3 NRU PT试验中用这两种方法获得的结果在9个实验室中是可重复的，并且体外和体内数据之间的相关性非常高。因此，ECVAM和COLIPA从这项盲法条件下的正式验证试验得出结论，3T3 NRU PT试验是一项经过科学验证的体外试验，已准备好被考虑用于监管目的以评估化学品的光毒性潜力。一份纳入3T3 NRU PT试验标准方案的经合组织“体外光毒性测试”准则草案将在适当时候提交给经合组织测试准则项目。
