Developmental toxicity assessment of neonicotinoids and organophosphate esters with a human embryonic stem cell- and metabolism-based fast-screening model

Abstract

In recent years, neonicotinoids (NEOs) and organophosphate esters (OPEs) have been widely used as substitutes for traditional pesticides and brominated flame-retardants, respectively. Previous studies have shown that those compounds can be frequently detected in environmental and human samples, are able to penetrate the placental barrier, and are toxic to animals. Thus, it is reasonable to speculate that NEOs and OPEs may have potential adverse effects in humans, especially during development. We employed a human embryonic stem cell differentiation- and liver S9 fraction metabolism-based fast screening model to assess the potential embryonic toxicity of those two types of chemicals. We show that four NEO and five OPE prototypes targeted mostly ectoderm specification, as neural ectoderm and neural crest genes were down-regulated, and surface ectoderm and placode markers up-regulated. Human liver S9 fraction's treatment could generally reduce the effects of the chemicals, except in a few specific instances, indicating the liver may detoxify NEOs and OPEs. Our findings suggest that NEOs and OPEs interfere with human early embryonic development.