Stereo-electronic Factors in Molecular Similarity and Risk Assessment

Abstract

Three strategic tasks for the risk assessment of the chemicals can be defined nowadays. The first one is related to the critical evaluation of the existing test data. For example, in the area of industrial chemicals, after exploration the availability of toxicity endpoints, the National Research Council concluded that for many of these chemicals minimum of tests or, in many cases, no tests at all are performed [1]. On the other hand, the available test data mostly consist of acute toxicity and eye/skin irritation tests. Recently, an analysis of an environmental database of more than 30,000 chemicals showed [2] that the total number of chemicals possessing measured values of either boiling/melting points or vapor pressure is only 3,692. The second task should handle the identification problem of potential analogues of chemicals. An effective solution of this problem based on similarity methods can allow the selection of analogues of a query chemical possessing similar (hazardous) properties. The third task is closely related with the second one and is directed to estimating the properties of chemicals by using quantitative structure-activity relationships (QSAR) models.