Genotoxicity tests for new chemicals in Germany: routine in vitro test systems

Abstract

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.