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2003
Book
Titel
Extrapolation from results of animal studies to humans for the endpoint male fertility
Abstract
Several reviews as well as studies on individual compounds have been analyzed with respect to the suitability of different study designs and endpoints to detect effects on male reproduction in animal species. LOAELs in animals and in humans have been compared in order to find general principles for the extrapolation from animals to humans. Histopathology of the testes was the most sensitive endpoint. If appropriate fixation and embedding techniques are used, effects can be detected already after 4 weeks of treatment with high sensitivity. Other sensitive parameters were weights of reproductive organs including assessory glands i. e. testis, epididymis, prostate, seminal vesicle weight and sperm parameters such as sperm count, sperm morphology and sperm motility, the latter being especially important as it is more sensitive than histopathology in some cases. Due to the high variation of several of these parameters, only pronounced effects can be detected. Laboratory animals are still fertile even if the sperm counts drop by 90 to 99%. Consequently, in fertility studies, fertility parameters showed lower sensitivity than the other parameters. In most cases not a single endpoint but rather several endpoints were affected. A high correlation was found for detection of reproductive toxicity in continuous breeding studies and in 90 day studies with additional measurement of sperm parameters.