COLLABORATIVE WORK TO EVALUATE TOXICITY ON MALE REPRODUCTIVE ORGANS BY REPEATED DOSE STUDIES IN RATS : 6)2-AND 4-WEEKS ADMINISTRATION STUDY OF HALOPERIDOL

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Haloperidol, a neuroleptic, was orally given to Sprague-Dawley rats for 2 or 4 weeks, starting at 8 and 6 weeks of age. The dose levels were 0, 30 and 60 mg/kg/day for the 4-week treatment groups, and 0, 30, 60 and 80 mg/kg/day for the 2-week treatment groups. On the day after the last administration, rats were anesthetized and sacrificed at 10 weeks of age. The absolute weights of the testes and epididymides were decreased after 2-and 4-weeks at 30 mg/kg/day or above. The absolute and relative weights of the prostate and seminal vesicles were also decreased after 2-weeks at 60 mg/kg/day or above, and 4-weeks at 30 mg/kg/day or above. The histopathological alterations observed after 2-weeks at 30 mg/kg/day were as follows : atrophy of Leydig cells, numerous necrotic pachytene spermatocytes in seminilferous tubules of stage VII, retention of mature spermatids, exfoliation of round spermatids in lumina of scminiferous tubules, cell debris in lumina of the epididymis. At 60 mg/kg/day or above, these alterations were pronounced. Histopathological changes were comparable to those detected after 4-weeks treatment. It was concluded that alterations of the male reproductive organs are detectable by a 2-week administration of haloperidol in rats to almost the same degree as after 4-weeks treatment.
日本トキシコロジー学会の論文
2000-10-25