(Q)SARs for Predicting Effects Relating to Reproductive Toxicity

Abstract This paper reviews the current status of structure‐based methods for predicting adverse reproductive effects in mammals. The methods described include (Quantitative) Structure–Activity Relationships ((Q)SARs), expert systems and the less formalised approaches of read‐across within (chemical) categories. There are a number of problems with applying QSARs to reproductive toxicology notably the complexity, subtlety and sometimes ill‐defined nature of the endpoints and lack of data available for modelling. A small number of ((Q)SARs have been developed for individual classes of compounds for well‐defined effects. These are supplemented by expert systems approaches of all types [ e.g. DEREK for Windows, TOPKAT, MC4PC, PASS, Organisation for Economic Co‐operation and Development (OECD) QSAR Application Toolbox] for a variety of endpoints associated with reproductive toxicology. By far the largest, and best developed, group of models are those for receptor binding effects related to endocrine disruption, in particular to the Oestrogen Receptor (ER) and, to a lesser extent, the Androgen Receptor (AR). Strategies to improve predictive capabilities for reproductive toxicology are suggested.