28-day toxicology test: indenopyridine RTI 4587-056 in male Sprague-Dawley rats.
The potential toxicity of RTI 4587-056, a hexahydroindenopyridine analog of SANDOZ 20-438, was examined in adult male Sprague-Dawley rats. Testicular, intestinal, and erythropoietic histology was assessed after 28 days of gavage treatment at 0, 10, and 100 mg/kg/day. During the first 10 days, dose-related clinical signs included mild to moderate lethargy shortly after dosing, lower consumption of feed and water, and body weight loss or decreased weight gain. Tolerance developed, such that lethargy disappeared and weight gains were equivalent to the control group during the second through fourth weeks. The compound did not affect intestinal epithelium or bone marrow. RTI 4587-056 was a highly effective antispermatogenic agent at both doses causing epididymal hypospermia and testicular atrophy. Based upon the Spermatogenic Index ratings, still lower doses would be effective male contraceptive agents. RTI 4587-056 has potential as a male contraceptive without overt side effects. Further testing is required.
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Chemistry and Life Sciences Unit, Research Triangle Institute, P.O. Box 12194, Research Triangle Park, NC 27709-2194, USA. patf@rti.org
Anderson
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Cook
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D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D019963:Clinical Chemistry Tests; D003272:Contraceptive Agents, Male / Q000633:toxicity*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006403:Hematologic Tests; D007422:Intestines / Q000187:drug effects / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011725:Pyridines / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012670:Seminiferous Epithelium / Q000187:drug effects / Q000473:pathology; D012894:Sleep Stages / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000473:pathology; D018675:Toxicity Tests
D003272:Contraceptive Agents, Male; D011725:Pyridines; C411384:RTI 4587-056