Adverse effects of the antifertility agent DL 717-IT (Canocenta, Byk Gulden, FRG). Pathological findings in the rabbit.
The post-coital antifertility agent DL 717-IT (Canocenta, Byk Gulden, FRG) was administered to sixteen female (5 pregnant and 11 nonpregnant) New Zealand White (NZW) rabbits by single i.m. injections at a dose of 2.5 mg/kg body weight. The corresponding number of controls received the vehicle of the drug only. Pregnancy was interrupted in all the DL 717-IT-treated rabbits. Obvious loss of bodyweight (-15% at mean) was observed in all the test animals during the first two test weeks after treatment. Same sized groups of test and control animals were euthanasized 3, 4, 5, and 6 weeks after the initiation of the treatment and complete necropsies and histological examinations were performed. One of the test animals died on day 21. Pathological findings involved epidermal hyperplasia, hyper- and dyskeratosis seen in 16/16, zonal and massive liver necrosis in 8/16, generalized degeneration of the skeletal muscles in 6/16, and focal myocardial necrosis in 5/16 test animals. Vitamin A concentrations in liver tissue were found to be significantly reduced in the experimental animals compared to the controls. Consequently the skin lesions may possibly be explained as the result of reduced vitamin A synthesis due to DL 717-IT-induced hepatocellular damage. The results of this study indicate severe toxic effects of DL 717-IT in the given formulation in the rabbit at dosages reported to be well tolerated in several species and recommended for veterinary use to terminate unwanted pregnancies in the bitch.
Wanke
R
R
Institute of Veterinary Pathology, Veterinary Faculty, University of Munich, FRG.
Hermanns
W
W
D000019:Abortifacient Agents / Q000633:toxicity*; D000020:Abortifacient Agents, Nonsteroidal / Q000633:toxicity*; D000818:Animals; D005260:Female; D007546:Isoquinolines / Q000633:toxicity*; D008099:Liver / Q000473:pathology; D011247:Pregnancy; D011817:Rabbits; D012867:Skin / Q000473:pathology; D014801:Vitamin A / Q000032:analysis
D000019:Abortifacient Agents; D000020:Abortifacient Agents, Nonsteroidal; D007546:Isoquinolines; D014801:Vitamin A; C053658:lotrifen