Effect of intrauterine administration of tetracyclines on cynomolgus monkeys

Cynomolgus monkeys were used to screen for chemicals which potentially could be used as tubal occluding agents. Intrauterine administrations of solution or pellets of tetracycline and its analogues (100 mg doses) were tested for their effects on morphologic changes in the reproductive tract of monkeys. These effects were compared to monkeys receiving intrauterine administration of quinacrine pellets (36 mg) since quinacrine has been used successfully in the clinical setting. Blood levels of drugs, blood chemistry and hematology determinations and liver and kidney pathology data were also obtained as indices for toxicity. Morphologic damage to the uterine lining and intramural section of the tube (including necrosis, inflammation or scarring) was elicited by intrauterine tetracycline and doxycycline in the same frequency and severity as quinacrine. In contrast, saline or sham control monkeys showed no morphological damage of the tube or uterus. Although all drugs could be detected in the blood 4 hours after intrauterine administration, levels were near or below the limit of detection by one week. No evidence was found for toxicity of tetracycline or its analogues for the dosage given. Because of these results and the extensive literature on tetracycline toxicity, further studies should be directed toward the use of tetracycline as a sterilizing agent in women.