Possible role of the blood-testicular barrier in dominant lethal testing.

During dominant-lethal testing for mutagenic effects, chemicals are usually administered intraperitoneally or orally to male animals as a single dose. These treated animals are subsequently housed for mating with virgin females which are replaced at weekly intervals. For screening purposes, a reduction in total living implants is monitored as an indication of the induction of chromosomal anomalies which result in fetal deaths. This serial mating approach further allows the investigator to identify the spermatogenic cell type affected by the test chemical (1). It is generally assumed that the test chemical gains access readily to the cells in the seminiferous tubules, tubuli recti, rete teste, efferent ducts, epididymis, and vas deferens. However, such an assumption ignores many pharmacokinetic concepts regarding the distribution of chemicals in the body and the role of biologic barriers (2). An especially important barrier in this regard could be the so-called blood-testicular barrier which has been adequately described only in the last few years (3-6). These reports and recent studies in our own laboratory (7, 8) as well as other physiologic and anatomical aspects of the testes suggest the possibility of many "false negative" results of the dominant-lethal test, i.e., instances where