RESUMEN
Organophosphorus compounds or organophosphates (OPs) are widely used as flame retardants, plasticizers, lubricants and pesticides. This contributes to their ubiquitous presence in the environment and to the risk of human exposure. The persistence of OPs and their bioaccumulative characteristics raise serious concerns regarding environmental and human health impacts. To address the need for safer OPs, this study uses a New Approach Method (NAM) to analyze the neurotoxicity pattern of 42 OPs. The NAM consists of a 4-step process that combines computational modeling with in vitro and in vivo experimental studies. Using spherical harmonic-based cluster analysis, the OPs were grouped into four main clusters. Experimental data and quantitative structure-activity relationships (QSARs) analysis were used in conjunction to provide information on the neurotoxicity profile of each group. Results showed that one of the identified clusters had a favorable safety profile, which may help identify safer OPs for industrial applications. In addition, the 3D-computational analysis of each cluster was used to identify meta-molecules with specific 3D features. Toxicity was found to correspond to the level of phosphate surface accessibility. Substances with conformations that minimize phosphate surface accessibility caused less neurotoxic effect. This multi-assay NAM could be used as a guide for the classification of OP toxicity, helping to minimize the health and environmental impacts of OPs, and providing rapid support to the chemical regulators, whilst reducing reliance on animal testing.
