SUMMARY REPORT OF THE WORKING-GROUP-ON-MAMMALIAN-GERM-CELL-TESTS

The two tests considered by the Working Group were the mammalian germ cell cytogenetic assay and the rodent dominant lethal test. It was agr eed that both tests were mainly used for identification of germ cell h azards, however, that the commonly applied protocol of the dominant le thal assay often supplied information for hazard characterization such as sensitivity of particular developmental stages of male germ cells. No particular species or strains were indicated. Concurrent solvent c ontrols were regarded as indispensable for both tests. In the discussi on of the mammalian germ cell cytogenetic assay, harmonization was obt ained to a large extent with the cytogenetic bone marrow assay regardi ng the number of animals (5), the number of cells analyzed per animal (200), the highest exposure dose (MTD) and sampling times (twice withi n 24 and 48 h after dosing). However, it was pointed out that only the single acute exposure was adequate for the mammalian germ cell cytoge netic assay. Furthermore, it was stated that only structural chromosom e aberrations could be analyzed and that it was not informative to sco re polyploidies or aneuploidies. In the discussion of the rodent domin ant lethal test, it was stated that the assay was generally performed with treated males, however, increasing concern about female specific effects required that a protocol for female dominant lethal testing sh ould be developed and validated. Acute and subacute treatment schedule s were considered equally acceptable. It was regarded as highly import ant that the entire male germ cell development from meiosis to mature sperm was covered in the test protocol either by the appropriate matin g schedules after single dosing or by subchronic dosing during the res pective period. Postimplantation loss, preimplantation loss and fertil ity rate were the main parameters to be assessed in the rodent dominan t lethal tests. It was agreed that the size of the experiment depended on the spontaneous frequency of dead implants, the mating scheme and the statistical design of the experiment.