Spermatogenesis and mutagenicity of environmental hazards: extrapolation of genetic risk from mouse to man

To perform germ cell mutagenicity studies it is mandatory to know the duration of the different stages of spermatogenesis. The timing of male germ cell development determines the test protocols. Chemical mutagens are characterized by their differential spermatogenic responses, e.g. different chemicals induce mutations in different germ cell stages. Knowledge of the sensitive germ cell stages for a test agent is essential for the evaluation of the genetic hazard, i.e. stem cell effects present permanent genetic hazards and post-stem cell effects present transient hazards. A variety of assays are available to determine germ cell mutagenicity in treated animals or in the progeny of treated animals. Germ cell cytogenetics in differentiating spermatogonia and the dominant lethal assay are used for genetic hazard identification. Their results allow categorization of chemicals as germ cell mutagens (Maximale Arbeitsplatz Konzentration categories for germ cell mutagens). Gene mutations or reciprocal chromosome translocations induced in germ cells are assessed by observation of mutant offspring of treated males. These results are applicable to the quantification of genetic hazards for chemical exposures which cannot be avoided, i.e. for occupational exposures to chemicals such as butadiene.