SPECIAL REQUIREMENTS FOR TOXICOLOGICAL TESTING OF METAL-RELEASING INTRAUTERINE DEVICES

Abstract

Intrauterine devices (IUD's), intrauterine drug reservoirs (IUDR's), and metal-releasing intrauterine drug reservoirs (MR-IUDR's) with antifertility activity in the animal and human are considered as separate entities. General requirements for toxicologic and teratologic testing of such agents in animals are presented. A comparison reveals the relative advantages and disadvantages of simian, canine, lagomorph, and rodent species. A pretreatment review of obstetric-gynaecologic status and history of each animal is emphasized. Designing of appropriate replicas of the clinical device for use in predictive animal studies requires comparative data on uterine morphology, device-endometrium spatial relationships, and drug release rates. Adult, maternal and foetal tissue metal levels may be important; the analytical methods for detecting and localizing cellular and subcellular wet tissue metal levels are available. Existing in vivo mutagenicity assay procedures are poorly adapted to intrauterine drug testing. Method modifications are explored briefly. A sequence for the animal safety testing of an intrauterine antifertility agent, and its interrelation with clinical research, is outlined.