QSAR modeling of cumulative environmental end-points for the prioritization of hazardous chemicals.

The hazard of chemicals in the environment is inherently related to the molecular structure and derives simultaneously from various chemical properties/activities/reactivities. Models based on Quantitative Structure Activity Relationships (QSARs) are useful to screen, rank and prioritize chemicals that may have an adverse impact on humans and the environment. This paper reviews a selection of QSAR models (based on theoretical molecular descriptors) developed for cumulative multivariate endpoints, which were derived by mathematical combination of multiple effects and properties. The cumulative endpoints provide an integrated holistic point of view to address environmentally relevant properties of chemicals. Environmental significance The majority of existing compounds has not been sufficiently well characterized for environmental behaviour and potential human or ecological toxicity. Screening methods are needed to prioritize the most hazardous chemicals. In this way, it is possible to reduce costs, time and number of sacrificed animals. Here we present our approach, based on the combination of Principal Component Analysis (PCA) and Quantitative Structure Activity Relationship (QSAR) models, applied to study environmental persistence, aquatic toxicity and PBT behaviour of different classes of organic chemicals. Such an approach may be particularly useful for the identification of new emerging pollutants and also for planning a priori the synthesis of safer alternatives to undesired chemicals, according to the benign structural design approach of Green Chemistry.