Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 8). Effects of daily subcutaneous administration of reserpine on spermatogenesis for 2 and 4 weeks.
To obtain information on the validity and the limitations of 2-weeks repeated-dose toxicity studies to detect effects on the male genital organs of rats, reserpine was administered daily at 0.05 and 0.1 mg/kg by subcutaneous injection to Crj:CD(SD)IGS male rats for 2 and 4 weeks (2-weeks and 4-weeks studies). In the 2-weeks study, suppression of body weight gain was observed in the reserpine 0.1 mg/kg group. In the 4-weeks study, suppression of body weight gain and a decrease in prostate weight were observed in the reserpine 0.1 mg/kg group. Slight to moderate retention of step 19 spermatids in the seminiferous tubules (stages IX-XI) was observed in a few animals of both the reserpine 0.05 and 0.1 mg/kg groups in both the 2- and 4-weeks studies. However, seminiferous tubule atrophy with degeneration of germ sells was observed sporadically not only in the reserpine groups but also in the control group, and this change might have been the cause of the spermatid retention. Therefore, we were unable to reach a clear conclusion with regard to whether it is possible to detect reserpine toxicity on spermatogenesis in rats after 2-weeks administration.
Kawamura
N
N
Drug Innovation & Approval Division, Aventis Pharma Ltd., 1-3-2 Minamidai, Kawagoe, Saitama 350-1165, Japan.
Tsutsumi
S
S
Takeshita
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000633:toxicity*; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009929:Organ Size / Q000187:drug effects; D011467:Prostate / Q000187:drug effects / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000008:administration & dosage / Q000633:toxicity*; D012671:Seminiferous Tubules / 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; D015430:Weight Gain / Q000187:drug effects
D000959:Antihypertensive Agents; D012110:Reserpine