Broschinski L, Madle S, Hensel C
Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV), Postfach 330013, D-14191, Berlin, Germany.
Mutat Res. 1998 Oct 12;418(2-3):121-9. doi: 10.1016/s1383-5718(98)00119-3.
According to regulations in the European Union, new chemical substances must be notified before they can be introduced onto the market. One of the prerequisites for notification is that toxicological properties, including mutagenicity, are examined. In this paper, a report on routine in vitro mutagenicity testing is given for 776 new substances notified in Germany between 1982 and 1997. In general, the methodological quality of testing was in line with internationally accepted guidelines. Bacterial gene mutation tests (Bact) were conducted for nearly all of the substances, 13.4% were positive. Of the Bact-positive substances, 36 were also tested in the in vitro chromosomal aberration test (CAbvit) and the mammalian cell gene mutation test (MCGM). Twenty-six of these (72. 2%) were negative in both mammalian cell tests indicating that the genotoxic potentials of the substances are not relevant for man. Of all new substances, 333 were tested in CAbvit, here the percentage of positive findings was 25.2%. More than 80% of the in vitro clastogens were negative in the Bact. With respect to a sensitive detection of genotoxic potentials of substances, the combination 'Bact+CAbvit' is appropriate for basic testing. In our database CHL cells were more sensitive to clastogenic effects than other cell types. Only very few clastogens were identified as 'high toxicity clastogens'. MCGM tests were performed for 118 substances, quite often as follow-up in case of positive Bact tests. In total, 12.7% of the substances were positive in the MCGM. However, there was a clear difference in the frequencies of positive findings in HPRT tests (5.5%) and mouse lymphoma assays (MLA; 37.0%). None of the MCGM-positive substances was a 'unique positive', i.e., negative in Bact and CAbvit.
根据欧盟的规定，新化学物质在投放市场之前必须进行通报。通报的前提条件之一是要对包括致突变性在内的毒理学特性进行检测。本文给出了1982年至1997年间在德国通报的776种新物质的常规体外致突变性检测报告。总体而言，检测的方法学质量符合国际公认的准则。几乎对所有物质都进行了细菌基因突变试验（Bact），其中13.4%呈阳性。在Bact试验呈阳性的物质中，有36种还进行了体外染色体畸变试验（CAbvit）和哺乳动物细胞基因突变试验（MCGM）。其中26种（72.2%）在两种哺乳动物细胞试验中均为阴性，这表明这些物质的遗传毒性潜力与人类无关。在所有新物质中，有333种进行了CAbvit试验，此处阳性结果的百分比为25.2%。超过80%的体外断裂剂在Bact试验中呈阴性。就灵敏检测物质的遗传毒性潜力而言，“Bact+CAbvit”组合适用于基础检测。在我们的数据库中，CHL细胞比其他细胞类型对断裂效应更敏感。只有极少数断裂剂被鉴定为“高毒性断裂剂”。对118种物质进行了MCGM试验，通常是在Bact试验呈阳性的情况下作为后续检测。总体而言，12.7%的物质在MCGM试验中呈阳性。然而，在次黄嘌呤-鸟嘌呤磷酸核糖转移酶试验（HPRT；5.5%）和小鼠淋巴瘤试验（MLA；37.0%）中阳性结果的频率存在明显差异。没有一种MCGM试验呈阳性的物质是“唯一阳性”，即在Bact和CAbvit试验中呈阴性。
