Evaluation of developmental toxicity of chlorpyrifos through new approach methodologies: a systematic review

Chlorpyrifos (CPF) is an organophosphorus pesticide of concern because many in vivo animal studies have demonstrated developmental toxicity exerted by this substance; however, despite its widespread use, evidence from epidemiological studies is still limited. In this study, we have collected all the information generated in the twenty-first century on the developmental toxicity of CPF using new approach methodologies. We have critically evaluated and integrated information coming from 70 papers considering human, rodent, avian and fish models. The comparison of the collected evidence with available adverse outcome pathways allows us to conclude that adverse outcomes observed in animals, such as memory and learning impairments as well as reduction in cognitive function, could involve several mechanisms of action including inhibition of acetylcholinesterase, overactivation of glutamate receptors and activation of mitogen-activated protein kinase, extracellular signal-regulated kinase 1/2, followed by both disruption of neurotransmitter release and increase in oxidative stress and apoptosis.