Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 4). Fadrozole hydrochloride: an oral 2/4-week male reproductive organ toxicity study.
Doses of 0, 30 and 60 mg/kg/day of fadrozole hydrochloride (Afema: non-steroidal aromatase inhibitor, antitumor agent) were given perorally by gavage to HanIbm WIST male rats from 6 or 8 weeks of age for 2 weeks, and from 6 weeks of age for 4 weeks. In all treatment groups, reduced weights of seminal vesicle, prostate and epididymis, and degeneration/necrosis of the pachytene spermatocytes in stages VII or VIII seminiferous tubules, were dose-relatedly observed. Effects could also be assessed quantitatively by staging analysis with the result of a reduction in the numbers of stage VII pachytene spermatocytes at 30 and 60 mg/kg/day. Epididymal sperm examination revealed no treatment-related changes in any groups. The effects of 4-week treatment on male reproductive organs were similar to those of 2-week treatment at the same dose levels, except for the weights of seminal vesicle and prostate, which were more reduced by 4-week treatment than by 2-week treatment. There was no notable difference in detectability of toxicity in male reproductive organs between 2-week treatment from 6 weeks of age and 2-week treatment from 8 weeks of age. It was concluded that the changes observed in the rat male reproductive organs following 4 weeks of treatment with fadrozole hydrochloride could be detected also with 2 weeks of treatment.
Kawashita
H
H
Toxicology/Pathology, Tsukuba Research Institute, Novartis Pharma K. K., 8 Ohkubo, Tsukuba, Ibaraki 300-2611, Japan.
Hiratsuka
K
K
Kuroda
J
J
Asada
Y
Y
Suzuki
T
T
Muguruma
Y
Y
Tomioka
S
S
Tani
M
M
Kondo
M
M
Mineshima
H
H
Nagae
Y
Y
D000284:Administration, Oral; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D017316:Fadrozole / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D013076:Sperm Count; D013081:Sperm Motility / Q000187:drug effects; D013737:Testis / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D018675:Toxicity Tests; D015430:Weight Gain / Q000187:drug effects
D018931:Antineoplastic Agents, Hormonal; D004791:Enzyme Inhibitors; D017316:Fadrozole