Quantitative and qualitative structure activity relationships in developmental toxicity.

Abstract

Quantitative and qualitative structure activity relationships (QSAR’S) have been used for many years in the design of new drugs but it is only in the last 15 years that they have been used as mechanistic tools and to provide early hazard warnings in Toxicology. These applications have become more complex progressing from acute investigations, often in non-mammalian species where treatment and response are closely linked, to chronic studies of carcinogenicity. The application of QSAR’s to studies of developmental toxicity represents the most testing challenge to date. These studies differ from other investigations in that, in vivo, two interrelated experimental systems (the mother and the foetus) are involved. There are many endpoints and many factors contribute to the effects observed. Considering the requirements for a valid QSAR, according to the ECETOC report of 1986, “The biological activity under consideration involves a single, simple mechanism and a well-defined endpoint”, can structure activity relationships be applied to such a complex area as teratology investigations?