Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 3). Effects of repeated doses of ethinylestradiol for 2 and 4 weeks on the male reproductive organs.

Abstract

Male Sprague-Dawley rats were subcutaneously administered 0.3 and 3.0 mg/kg/day of ethinylestradiol for 2 and 4 weeks. Two weeks treatment decreased body weight gain, food consumption, absolute weights of testis, epididymis, prostate and seminal vesicle, and relative weights of epididymis, prostate and seminal vesicle. On the other hand, it increased absolute and relative weights of pituitary and adrenal glands, and induced atrophy of Leydig cells, degeneration/necrosis of pachytene spermatocytes, vacuolar degeneration of Sertoli cells, and retention of spermatids. In addition to the changes found after 2 weeks treatment, 4 weeks treatment induced exfoliation of germinal cells, decreases in spermatid and multinucleated giant cell formation and relative weights of testis. These results suggest that examination of prostate and seminal vesicle weights and histopathological changes in the testis are important for evaluation of male reproductive toxicity of ethinylestradiol and 2 weeks treatment is sufficient to detect toxicity on male reproductive organs.