Pesticides Research, 94 – Quantitative Structure-Activity Relationships (QSAR) and Pesticides

Quantitative Structure-Activity Relationships (QSAR) and Pesticides

Preface

This study considers the current available knowledge on the use of Quantitative Structure-Activity Relationship (QSAR) models relating to the use on pesticides.

The use is based on evaluation of the correlations between experimental values and QSAR estimates from the selected QSAR models. The experimental values are obtained from Pesticide Manual (Tomlin 1994, 1997), Linders et al. (1994), and from letters of approval for plant protection preparations containing data from studies submitted by manufacturers to the Danish Environmental Protection Agency (Danish EPA) and evaluated in internal reports (Clausen 1998).

QSARs are quantitative models seeking to predict activity such as environmental toxicity derived from the molecular structure. Most often this is accomplished by first correlating properties such as physico-chemical parameters with molecular structure and then correlating toxicity with these parameters. The central paradigm underlying such QSAR modelling is the structure-property similarity principle. This paradigm states that analogous structures have generally similar properties. Since chemicals with similar properties tend to have similar biological activities, toxicity may be predicted from structure alone. More than six million chemical substances are known and humans are exposed to 50,000 to 100,000 of them. As it is impossible to test each substance in a time and cost effective manner, this “guilt by association” approach provides a powerful alternative to direct testing for predicting toxicity for untested substances. While QSARs in environmental toxicology were reported as early as 1869, modern efforts have their roots in the classic turn of the century work of Meyer and Overton on narcotics.

Narcosis is the reversible state of arrested protoplasmic activity. It is a physical phenomenon, which is mostly independent of specific molecular structure. It is considered the most common mode of toxic action, at least in short term exposure of aquatic organisms, and the mode of action for about 70% of the industrial organic chemicals. Narcosis is subdivided into several non-specific and specific mechanisms (e.g. non-polar narcosis, polar narcosis etc.).

However, pesticides are developed specifically based on their specific mode of action mechanisms and this may affect the predictability of QSARs.

Based on the work already performed, the present report uses the most promising descriptors. As most of the preliminary work has been done on simpler molecules an evaluation at this stage may result in a less promising result. However, it has been found reasonable to perform such an analysis to assess the current stage of the use of QSARs on pesticides.