The potential connections of adverse outcome pathways with the hazard identifications of typical organophosphate esters based on toxicity mechanisms

Abstract

Following the world-wide ban of brominated flame retardants (BFRs), organophosphate esters (OPEs), which could potentially affect human health and ecosystem safety, have been frequently detected in various environmental media. However, the knowledge regarding the underlying toxicity effects of OPEs remains limited. In order to address these issues, this study reviewed the related reports which have been published in recent years. This analysis process included 12 OPEs, 10 model organisms, and 15 cell lines, which were used to systematically examine the mechanisms of endocrine disruption, neurotoxicity, hepatotoxicity, and cardiotoxicity, as well as reproductive and developmental toxicity. Subsequently, an adverse outcome pathway (AOP) framework of the toxicological effects of OPEs was built. The results demonstrated that multiple different pathways may lead to a single same adverse outcome (AO), and there was a certain degree of correlation among the different AOs. It was found that among all the 12 OPEs, tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) may potentially be the most toxic. In addition, rather than the parent chemicals, the metabolites of OPEs may also have different degrees of toxicity effects on aquatic organisms and humans. Overall, the results of the present study also suggested that an AOP framework should be built via fully utilizing the existing toxicity data of OPEs based on in vivo-in vitro-in silico to completely and deeply understand the toxic mechanisms of OPEs. This improved knowledge could then provide a theoretical basis for ecological risk assessments and water quality criteria research in the near future.

Keywords: Adverse outcome pathway; Endocrine disruption; Hepatotoxicity and cardiotoxicity; Neurotoxicity; Organophosphate esters; Reproductive and developmental toxicity.