Predictiveness and limitations of test methods in teratology: overview.

Compounds intended for marketing by the pharmaceutical industry are tested for possible effects on reproductive processes in much the same way today as was carried out even before November 1961, when the drug thalidomide was related to human malformations. At that time, effects on male and female fertility were sought, but generally only for agents considered likely to alter the endocrinologic status of the patient or that were designed primarily for use by young women. The test species was usually the rat. When it became evident that this system did not detect the teratogenic potential of thalidomide, it was realized that a model that would detect this type of activity was needed. Thalidomide was under study in my laboratory at the William S. Merrell Company (1) within three days of Lenz's announcement of the relationship between thalidomide and human malformations. Hence, routine testing was being conducted in at least one industrial laboratory when the FDA guidelines were circulated in 1966. These guidelines and the principles published by WHO in 1967 have been followed by private industry, which has conducted most of the routine testing carried out to date to determine the teratogenic potential of agents. These test results on prospective therapeutic agents now represent most of the information available on the teratogenic potential of chemicals. With the increased commitment of resources currently available for the testing of additional components of our environment, it is necessary to determine whether such test procedures are doing the job.