In-vitro tests for the long-term safety evaluation of drugs offer certain advantages. Specific properties of drugs can be identified including mutagenic and carcinogenic effects. The mechanisms leading to toxicity can be assessed. Tissue from several species, including man, can be examined. These tests should reduce the number of animal tests required for screening new drugs.
PIP: Some evidence exists that in-vitro studies are capable or potentially capable of providing more rapid, precise, and relevant information than do some animal studies. At this time, the primary use of in-vitro tests is the detection of specific toxic properties of drugs and chemicals, e.g., mutagenesis and mechanisms of toxicity. The theoretical basis for this stems from the commonality of the basic structure and behavior of genetic material whereby in-vitro tests for genetic toxicology can replace animals tests. Additionally, replacement of animal testing by in-vitro techniques depends on the validity of the assumption that the wide range of manifestations of toxicity observed in vivo are triggered by a relatively small number of identifiable initiating events. The screening of drugs for a particular adverse property currently is the most applicable use of in-vitro tests. In practice the development of in-vitro tests most likely will proceed in at least 2 distinct phases: identification by a series of individual tests of the fundamental biological properties of the test drug; and findings detected in the phase 1 tests would be investigated in more sophisticated versions of the test, and these phase 2 tests usually would be of much longer duration. Table 1 lists the vast range of cells and tissues which have been used for in-vitro tests and details some of those most relevant to preclinical testing of drugs in the field of fertility regulation. The tests fall into the categories of microbiological tests, fungal cultures, tissue culture teratogen assays, cytoxicity tests -- sensitivity of tissues, and sperm tests in toxicology. There has been a reduction in confidence in animal studies in the safety evaluation of oral contraceptives (OCs). This has led to their rejection as indicators of significant hazards to women. Consequently, a number of short-term in-vitro tests have been accepted by the regulatory authorities. Of these, the Ames test is the most popular. A variety of genetic assays have been developed which involve the use of cultures of fungi. In these observations changes in the chromosome number can be assayed by selective plating techniques. Using primary cell cultures of 8-day chick embryo limb fibroblast cultures, it is possible to develop techniques which give some correlation with tests for teratogenicity on whole animals. The development of cytotoxicity assays as an alternative to the Draize test for acute inflammatory response in the eye of the adult rabbit raises the possibility of the evaluation of spermicides as a similar test system. Finally, sperm tests may provide valuable information in toxicological testing.