EVALUATION OF TESTICULAR TOXICITY IN SAFETY EVALUATION STUDIES - THE APPROPRIATE USE OF SPERMATOGENIC STAGING

Toxicology of the male reproductive system has received increased inte rest in recent years partly fuelled by the growing reports of falling sperm counts and rising reproductive disorders in the human population . Recently revised regulatory guidelines for the safety assessment of pharmaceuticals and chemicals on reproduction and fertility have empha sized the importance of detailed histopathological examination of the testes as a sensitive method for detecting disturbances in spermatogen esis. Unfortunately this has been accompanied by a general confusion r egarding a practical approach to undertaking such a detailed examinati on, particularly in respect to the use of spermatogenic or tubular sta ging to identify subtle disturbances in spermatogenesis. The ability t o identify tubular stages of the spermatogenic cycle in sections of te stis plus a good understanding of the spermatogenic process and its dy namics are essential in order to carry out a sensitive examination of testicular histopathology and to interpret the changes seen. A rationa l approach is required initially to detect and subsequently to charact erize toxic effects to the male reproductive system. It is important t hat a distinction is made between these two objectives since different study designs are required and different methodology may be employed to produce the type of information or data required.