Implications of germ cell cytogenetic tests in the regulatory process.

Abstract

As tests for germ cell cytogenetics are not prominent in any regulatory guidelines for assessment of product safety, it was decided to investigate the regulatory implications of germ cell cytogenetics by sending detailed questionnaires to contacts in 12 different regulatory agencies. The questionnaires covered three main sections: the basic principles governing if and when germ cell cytogenetics might be an acceptable alternative to a dominant lethal, heritable translocation or mouse specific locus test; what details of protocol would be desired in a male or female germ cell cytogenetic assay; the presentation of data and the criteria for a valid study and a positive result. Replies were received from seven of those contacted and some of the responses were personal rather than official. They may be summarized as follows. (i) Germ cell tests are rarely requested as a matter of course. Positive results in in vivo somatic cell cytogenetic tests and/or problems indicated in fertility/reproduction studies would suggest to some agencies a need for germ cell tests, but others believe they do not contribute to the assessment of risk for man. (ii) Where germ cell tests are indicated, a dominant lethal test (most often) or heritable translocation test (sometimes) would be seen as helpful in elucidating germ cell effects; the mouse specific locus test is rarely requested due to the large numbers of animals involved and the small number of laboratories with the relevant expertise. (iii) As most widely used germ cell cytogenetic assays do not detect inherited mutations or effects on meiotic processes, they were not readily accepted as alternatives.(ABSTRACT TRUNCATED AT 250 WORDS)