Assessing the reproductive toxicity of some (con)azole compounds using a structure–activity relationship approach

Abstract

The present research investigates the study of a set of 27 (con)azoles and their reproductive toxicity. (Con)azoles are used as fungicides and herbicides in agriculture for treatment of fruits, vegetables, cereals, and seeds, or as human antimycotic therapeutics. According to EEC Directive 91/414, active substances used in plant protection products must undergo reproductive toxicity testing. Reproductive toxicity is a complex biological endpoint, which includes many different biological processes and, therefore, it can only to a limited extent be assessed by a single quantitative structure–activity relationship (QSAR) model. The proposed SAR models are built using unsupervised methods, such as hierarchical clustering, principal component analysis and self-organizing maps, with the aim of studying the similarity relationships between structures. The molecular structures are represented with a set of topological and structural descriptors. The models showing clusters, closest neighbours or outliers may support the categorization and the classification of (con)azoles as potential reproductive toxicants.

Keywords:

• conazoles
• reproductive toxicity
• clustering
• classification

Acknowledgement

We thank the Agency of Research of R Slovenia (ARRS) for support of our research under contract P1-0017.