DETECTION OF EFFECTS ON MALE REPRODUCTION - A LITERATURE SURVEY

The ICH (International Conference on Harmonization of Technical Requir ements for Registration of Pharmaceuticals for Human Use) Guideline fo r Detection of Toxicity to Reproduction for Medicinal Products, adopte d at the Second ICH Conference in Orlando, FL, U.S.A., emphasized the need for research into the suitability of various methods for the dete ction of effects on fertility in males. The current project was undert aken to compare the efficiency of methods by evaluating reports in the open literature. The results of the examination of 117 substances or substance classes support the view that histopathology and organ weigh t analysis provide the best general-purpose means of detecting substan ces with the potential to affect male fertility. Examinations at up to 4 weeks of treatment appear to be as effective as examinations conduc ted at later times. Mating with females for detection of effects unrel ated to interference with sperm production appears to provide an optim al combination because adding other methodologies does not materially improve the detection rate. As to the timing of the mating trial, a 2- week premating period is as efficient as mating at 4 weeks and apparen tly more efficient than mating after prolonged premating treatment.