Current Status and Future Progress of Reproductive/Developmental Toxicity Test

Abstract

Currently, the European Centre for the Validation of Alternative Methods in the EU appears to be at the forefront of the development of alternative methods for developmental toxicity test (reproductive/developmental toxicity test). Why is it di‹cult to develop alternative methods for developmental toxicity test in comparison with other toxicity tests? In developmental toxicity test, chemical substancesˆrst enter the bloodstream and then reach the placenta via metabolism in the liver and other organs. After further metabolism in the placenta, chemical substancesˆnally reach the fetus, where they aŠect fetal development. The diŠerence in the in vivo route of chemical substances is an important reason for the di‹culty in the establishment of new methods for developmental toxicologic test in comparison with general toxicity tests. According to the EU, the use of``in silico'' techniques for developmental toxicity test may be di‹cult, and I agree with this. The in silico technique is basically a method for prediction of toxicologic eŠects from existing data, and cannot predict new eŠects, because data obtained by developmental toxicologic test are too complex. Three techniques are now being examined to overcome the di‹culty in changing the method of developmental toxicologic test: the technique utilizing embryonic stem cells; micromass culture technique; and the whole embryonic culture technique. In this symposium, the current status of developmental toxicity tests and the three techniques being examined in the EU are introduced, and opinions on future progress are presented.