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AbstractHeavy metals (arsenic and manganese), particulate matter (PM), benzene, toluene, ethylbenzene, xylenes (BTEX), polycyclic aromatic hydrocarbons (PAHs) and endocrine disrupting chemicals (EDCs) have been linked to significant neurodevelopmental health problems in infants, children and young adults. These substances are widely used in, or become byproducts of unconventional oil and natural gas (UOG) development and operations. Every stage of the UOG lifecycle, from well construction to extraction, operations, transportation and distribution can lead to air and water contamination. Residents near UOG operations can suffer from increased exposure to elevated concentrations of air and water pollutants. Here we focus on five air and water pollutants that have been associated with potentially permanent learning and neuropsychological deficits, neurodevelopmental disorders and neurological birth defects. Given the profound sensitivity of the developing brain and central nervous system, it is reasonable to conclude that young children who experience frequent exposure to these pollutants are at particularly high risk for chronic neurological diseases. More research is needed to understand the extent of these concerns in the context of UOG, but since UOG development has expanded rapidly in recent years, the need for public health prevention techniques, well-designed studies and stronger state and national regulatory standards is becoming increasingly apparent.

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