On the replacement of in vivo tests on germ cell mutagenicity and fertility impairment
2005
Vogel,R. | Klemm,M. | Genschow,E. | Seiler,A. | Liebsch,M. | Spielmann,H.
German. In contrast to drugs, industrial chemicals are not intended to be uptaken directly by humans. They mainly serve as intermediates for preparations and products. In case of proper use exposure to the general public seems, therefore, to be neglegible. However, uncontrolled exposure may happen e.g. by accidents. Often little is known about the toxicological profile of a chemical substance. Consequently, a risk on human health can not be estimated. Realizing this fatal situation, the EU enacted a Directive for the notification of new and existing chamicals. Impairment of fertility is one of the most important endpoints to be determined using in vivo generation studies, which are extremely time-, money-, and animal-consuming.Besides the prediction of a carcinogenic risk, one of the most important issues of mutagenicity data is the detection of adverse effects on gametes and thus on fertility as well as on early embryonal development in mammals. For this purpose tests on mammalian germ cells need to be conducted. In practice, however, germ cell tests are rarely used because of the costs and the number of animals required. Therefore, we tried to develop a sensitive and predictive in vitro test systeme, which could serve as a model for mammalian germ cells: Murine female and male embryonic germ cell lines had been established in our laboratory and their sensitivity upon mutagen/non-mutagen treatment had been tested in comparison to adult cell lines. Applying linear discriminant analysis, all test chemicals used could be classified correctly!
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