Beyond Cholinesterase Inhibition: Developmental Neurotoxicity of Organophosphate Ester Flame Retardants and Plasticizers.

Journal Article (Journal Article)

Background

To date, the toxicity of organophosphate esters has primarily been studied regarding their use as pesticides and their effects on the neurotransmitter acetylcholinesterase (AChE). Currently, flame retardants and plasticizers are the two largest market segments for organophosphate esters and they are found in a wide variety of products, including electronics, building materials, vehicles, furniture, car seats, plastics, and textiles. As a result, organophosphate esters and their metabolites are routinely found in human urine, blood, placental tissue, and breast milk across the globe. It has been asserted that their neurological effects are minimal given that they do not act on AChE in precisely the same way as organophosphate ester pesticides.

Objectives

This commentary describes research on the non-AChE neurodevelopmental toxicity of organophosphate esters used as flame retardants and plasticizers (OPEs). Studies in humans, mammalian, nonmammalian, and in vitro models are presented, and relevant neurodevelopmental pathways, including adverse outcome pathways, are described. By highlighting this scientific evidence, we hope to elevate the level of concern for widespread human exposure to these OPEs and to provide recommendations for how to better protect public health.

Discussion

Collectively, the findings presented demonstrate that OPEs can alter neurodevelopmental processes by interfering with noncholinergic pathways at environmentally relevant doses. Application of a pathways framework indicates several specific mechanisms of action, including perturbation of glutamate and gamma-aminobutyric acid and disruption of the endocrine system. The effects may have implications for the development of cognitive and social skills in children. Our conclusion is that concern is warranted for the developmental neurotoxicity of OPE exposure. We thus describe important considerations for reducing harm and to provide recommendations for government and industry decision makers. https://doi.org/10.1289/EHP9285.

Full Text

Duke Authors

Cited Authors

  • Patisaul, HB; Behl, M; Birnbaum, LS; Blum, A; Diamond, ML; Rojello Fernández, S; Hogberg, HT; Kwiatkowski, CF; Page, JD; Soehl, A; Stapleton, HM

Published Date

  • October 2021

Published In

Volume / Issue

  • 129 / 10

Start / End Page

  • 105001 -

PubMed ID

  • 34612677

Pubmed Central ID

  • PMC8493874

Electronic International Standard Serial Number (EISSN)

  • 1552-9924

International Standard Serial Number (ISSN)

  • 0091-6765

Digital Object Identifier (DOI)

  • 10.1289/ehp9285

Language

  • eng