Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children

Skogheim, Thea Steen; Weyde, Kjell Vegard Fjeldheim; Aase, Heidi; Engel, Stephanie M.; Surén, Pål; Øie, Merete Glenne; Biele, Guido; Reichborn‐Kjennerud, Ted; Brantsæter, Anne Lise; Haug, Line Småstuen; Sabaredzovic, Azemira; Auyeung, Bonnie; Villanger, Gro Dehli

doi:10.1016/j.envres.2021.111692

Cited by 49 publications

(31 citation statements)

References 96 publications

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“…We identify increased anxiety-like behaviors as a novel phenotype of PFOS neurotoxicity in the larval zebrafish using an adapted open-field test model (Kalueff and Stewart 2012, Ahmad and Richardson 2013, Richendrfer et al 2012). Anxiety is an associated symptom of several neurobehavioral disorders linked to PFAS exposures, including autism spectrum disorder and ADHD (Ode et al 2014, Skogheim et al 2021, Oh et al 2021, Shin et al 2020). PFOS-induced center avoidance has been observed in mice exposed during adulthood (Fuentes et al 2007), but developmental anxiety has not been previously reported.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of neural regulation and microglial responses to brain injury in larval zebrafish exposed to perfluorooctane sulfonate

Paquette

Martin

Rodd

et al. 2022

Preprint

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Pollution is a driving force in climate change and an important modifier of human health. Humans are chronically exposed to complex chemical mixtures and, correspondingly, researchers are disentangling the contribution of different contaminants to human neuropathologies. Per- and polyfluoroalkyl substances (PFAS) are biopersistent pollutants and, due to their diverse applications, have become global contaminants. Perfluorooctane sulfonate (PFOS), a prevalent PFAS congener, impairs humoral immunity; however, its impact on innate immunity is unclear. Given the critical roles of innate immune cells, namely microglia, in brain development and homeostasis, we asked whether exposure adversely affects microglial function. Herein, we demonstrate developmental PFOS exposure produces microglial activation and upregulation of the microglia activation gene p2ry12. PFOS-induced microglial activation heightened microglial responses to brain injury, in the absence of increased cell death or inflammation. Use of the photoconvertible calcium indicator CaMPARI revealed PFOS exposure heightened neural activity, while optogenetic silencing of neurons was sufficient to normalize microglial responses to injury. Exposure to perfluorooctanoic acid, an immunotoxic PFAS, did not alter neuronal activity or microglial behavior, further supporting a role for neural activity as a critical modifier of microglial function. Together, this study reveals how contaminant-induced changes in brain activity can shape brain health.

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Section: Discussionmentioning

confidence: 99%

Evaluation of neural regulation and microglial responses to brain injury in larval zebrafish exposed to perfluorooctane sulfonate

Paquette

Martin

Rodd

et al. 2022

Preprint

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“…Children’s exposure to PFAS is of particular concern. Due to their lower body weight and sensitive developmental period, children’s exposure may result in a greater body burden and higher health risks compared to adults. , Prenatal and/or postnatal exposure to several well-studied PFAS, especially perfluorooctanoic acid (PFOA), was associated with overweight and obesity, neurodevelopmental and behavioral problems, dyslipidemia, immunity including vaccine response and asthma, renal function, and age at menarche in children. ,− A recent update from the United States (US) Center for Disease Control and Prevention reported geometric mean concentrations of 3.38 and 4.15 μg/L of perfluorooctanesulfonic acid (PFOS), and 2.00 and 1.89 μg/L of PFOA, in serum samples collected in 2013–2014 in the United States for children ages 3–5 and 6–11 years, respectively . These geometric means were similar to those reported for the general population (4.99 and 1.94 μg/L for PFOS and PFOA, respectively), and suggest that children might be exposed to higher levels of PFAS, but sources and pathways are not well understood.…”

Section: Introductionmentioning

confidence: 99%

Per- and Polyfluoroalkyl Substances in North American School Uniforms

Xia

Diamond

Peaslee

et al. 2022

Environ. Sci. Technol.

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We analyzed 72 children’s textile products marketed as stain-resistant from US and Canadian stores, particularly school uniforms, to assess if clothing represents a significant route of exposure to per- and polyfluoroalkyl substances (PFAS). Products were first screened for total fluorine (total F) using particle-induced γ-ray emission (PIGE) spectroscopy ( n = 72), followed by targeted analysis of 49 neutral and ionic PFAS ( n = 57). PFAS were detected in all products from both markets, with the most abundant compound being 6:2 fluorotelomer alcohol (6:2 FTOH). Total targeted PFAS concentrations for all products collected from both countries ranged from 0.250 to 153 000 ng/g with a median of 117 ng/g (0.0281–38 100 μg/m 2 , median: 24.0 μg/m 2 ). Total targeted PFAS levels in school uniforms were significantly higher than in other items such as bibs, hats, stroller covers, and swimsuits, but comparable to outdoor wear. Higher total targeted PFAS concentrations were found in school uniforms made of 100% cotton than synthetic blends. Perfluoroalkyl acids (PFAAs) precursors were abundant in school uniforms based on the results of hydrolysis and total oxidizable precursor assay. The estimated median potential children’s exposure to PFAS via dermal exposure through school uniforms was 1.03 ng/kg bw/day. Substance flow analysis estimated that ∼3 tonnes/year (ranging from 0.05 to 33 tonnes/year) of PFAS are used in US children’s uniforms, mostly of polymeric PFAS but with ∼0.1 tonne/year of mobile, nonpolymeric PFAS.

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“…PFAS exposure has been associated with ADHD in some epidemiological studies. ,,− This association remains controversial, and other studies did not find consistent patterns of association between PFAS and ADHD. − The alteration of dopaminergic and serotonergic neurotransmission by PFAS exposure may also explain the mechanism for functional deficits attributed to ADHD. Hyperactivity, one of the key symptoms of ADHD, has been demonstrated in animal models exposed to PFAS as discussed in the previous paragraph.…”

Section: Functional Consequences Of Pfas Exposurementioning

confidence: 99%

Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes

Brown-Leung

Cannon

2022

Chem. Res. Toxicol.

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Per- and polyfluoroalkyl substances (PFAS) are a group of persistent environmental pollutants that are ubiquitously found in the environment and virtually in all living organisms, including humans. PFAS cross the blood–brain barrier and accumulate in the brain. Thus, PFAS are a likely risk for neurotoxicity. Studies that measured PFAS levels in the brains of humans, polar bears, and rats have demonstrated that some areas of the brain accumulate greater amounts of PFAS. Moreover, in humans, there is evidence that PFAS exposure is associated with attention-deficit/hyperactivity disorder (ADHD) in children and an increased cause of death from Parkinson’s disease and Alzheimer’s disease in elderly populations. Given possible links to neurological disease, critical analyses of possible mechanisms of neurotoxic action are necessary to advance the field. This paper critically reviews studies that investigated potential mechanistic causes for neurotoxicity including (1) a change in neurotransmitter levels, (2) dysfunction of synaptic calcium homeostasis, and (3) alteration of synaptic and neuronal protein expression and function. We found growing evidence that PFAS exposure causes neurotoxicity through the disruption of neurotransmission, particularly the dopamine and glutamate systems, which are implicated in age-related psychiatric illnesses and neurodegenerative diseases. Evaluated research has shown there are highly reproduced increased glutamate levels in the hippocampus and catecholamine levels in the hypothalamus and decreased dopamine in the whole brain after PFAS exposure. There are significant gaps in the literature relative to the assessment of the nigrostriatal system (striatum and ventral midbrain) among other regions associated with PFAS-associated neurologic dysfunction observed in humans. In conclusion, evidence suggests that PFAS may be neurotoxic and associated with chronic and age-related psychiatric illnesses and neurodegenerative diseases. Thus, it is imperative that future mechanistic studies assess the impact of PFAS and PFAS mixtures on the mechanism of neurotransmission and the consequential functional effects.

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Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children

Cited by 49 publications

References 96 publications

Evaluation of neural regulation and microglial responses to brain injury in larval zebrafish exposed to perfluorooctane sulfonate

Evaluation of neural regulation and microglial responses to brain injury in larval zebrafish exposed to perfluorooctane sulfonate

Per- and Polyfluoroalkyl Substances in North American School Uniforms

Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes

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