Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 16). Effects of short-term administration of carmofur on spermatogenesis.
Since morphological changes in the testes were observed in a 4 week repeated dose toxicity study of carmofur in rats, male Sprague-Dawley rats were administered the compound orally at 200 mg/kg by gavage for 11 days to assess the possibility of detecting abnormalities in spermatogenesis within a 2 week period. For comparison two studies were performed, treatment groups of fifteen and fourteen rats being given carmofur for 28 and 11 days, respectively. There were seven and nine rats that died or were killed in a moribund condition with 28 and 11 days treatment, respectively. Histopathologically, vacuolar degeneration of Sertoli cells, degeneration of elongated spermatids, exfoliation of round spermatids and multinucleated giant cell formation were observed in the testes of all animals and cell debris in ductus epididymidis was noted in almost all rats in the 28 days study. Exfoliation of round spermatids and multinucleated giant cell formation were detectable in two of five rats in the 11 days study, and vacuolar degeneration of Sertoli cells was also evident in four, though the changes were slight. No abnormalities were observed in the epididymides in the 11 days study. These results suggest that effects of carmofur on spermatogenesis can be detected with a treatment period of less than 2 weeks using histopathological examination of the testes. Therefore a 2-week repeated dose toxicity study has validity for detection of effects of carmofur on the male reproductive organs in the rats.
Furukawa
M
M
Institute of Biological Science, Mitsui Pharmaceuticals, Inc., 1900-1 Togo, Mobara, Chiba 297-0017, Japan.
Karakama
T
T
Kaji
M
M
Gomita
S
S
Yoshimura
M
M
Watanabe
N
N
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity*; D008136:Longevity / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D013091:Spermatogenesis / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests
D000970:Antineoplastic Agents; C017367:carmofur; D005472:Fluorouracil