Single and mixture per- and polyfluoroalkyl substances accumulate in developing Northern leopard frog brains and produce complex neurotransmission alterations

Foguth, Rachel; Hoskins, Tyler D.; Clark, George C.; Nelson, Madeline D.; Flynn, R. Wesley; Perre, Chloé de; Hoverman, Jason T.; Lee, Linda; Sepúlveda, Marı́a S.; Cannon, Jason R.

doi:10.1016/j.ntt.2020.106907

Cited by 37 publications

(37 citation statements)

References 42 publications

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“…While PFAS are most concentrated in protein rich tissues of the body, primarily the liver and serum, they have also been detected in nervous tissues of humans, experimentally exposed laboratory animals, and diverse taxa of environmentally exposed wildlife. In addition to humans, PFAS have been detected in the brains of numerous organisms, including mice, rats, frogs, fish, birds, and marine and arctic mammals ( Ahrens et al, 2009 ; Bogdanska et al, 2011 ; Rubarth et al, 2011 ; Shi et al, 2012 ; Greaves et al, 2013 ; Iwabuchi et al, 2017 ; Foguth R. M. et al, 2020 ). The concentrations of PFAS in the brain vary appreciably depending on duration and route of exposure, however, for the most well studied PFAS (PFOA and PFOS), accumulation in the brain is proportional to exposure dose ( Austin et al, 2003 ; Kudo et al, 2007 ; Cui et al, 2009 ; Cao and Ng, 2021 ).…”

Section: Pfas Uptake and Accumulation In The Brainmentioning

confidence: 99%

“…To our knowledge, only six in vivo studies have assessed the neurological consequences of exposure to mixtures of PFAS, or mixtures including PFAS and other toxicants. A mesocosm study in Northern leopard frogs ( Rana pipiens ) compared neurotransmitter levels in frog brains after larval exposure to 10 ppb PFOS or 10 ppb of a PFAS mixture, assessing one subset after 30 days of exposure and another after frogs reached metamorphosis ( Foguth R. M. et al, 2020 ). The PFAS mixture contained PFOS, PFHxS, PFOA, PFHxA, and PFHpA, in a ratio mimicking that measured in surface water at Clark’s Marsh, an aqueous film forming foam (AFFF) exposed site in Michigan ( Foguth R. M. et al, 2020 ).…”

Section: Neurotoxic Effects Of Co-exposures and Mixtures Of Pfasmentioning

confidence: 99%

“…A mesocosm study in Northern leopard frogs ( Rana pipiens ) compared neurotransmitter levels in frog brains after larval exposure to 10 ppb PFOS or 10 ppb of a PFAS mixture, assessing one subset after 30 days of exposure and another after frogs reached metamorphosis ( Foguth R. M. et al, 2020 ). The PFAS mixture contained PFOS, PFHxS, PFOA, PFHxA, and PFHpA, in a ratio mimicking that measured in surface water at Clark’s Marsh, an aqueous film forming foam (AFFF) exposed site in Michigan ( Foguth R. M. et al, 2020 ). Foguth et al (2020b) found that after a 30-days exposure, glutamate levels in the brain were significantly reduced in both exposure groups compared to control animals, however serotonin levels were reduced only in the brains of frogs exposed to the mixture.…”

Section: Neurotoxic Effects Of Co-exposures and Mixtures Of Pfasmentioning

confidence: 99%

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A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

et al. 2022

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Per- and polyfluoroalkyl substances (PFAS) are a class of structurally diverse synthetic organic chemicals that are chemically stable, resistant to degradation, and persistent in terrestrial and aquatic environments. Widespread use of PFAS in industrial processing and manufacturing over the last 70 years has led to global contamination of built and natural environments. The brain is a lipid rich and highly vascularized organ composed of long-lived neurons and glial cells that are especially vulnerable to the impacts of persistent and lipophilic toxicants. Generally, PFAS partition to protein-rich tissues of the body, primarily the liver and blood, but are also detected in the brains of humans, wildlife, and laboratory animals. Here we review factors impacting the absorption, distribution, and accumulation of PFAS in the brain, and currently available evidence for neurotoxic impacts defined by disruption of neurochemical, neurophysiological, and behavioral endpoints. Emphasis is placed on the neurotoxic potential of exposures during critical periods of development and in sensitive populations, and factors that may exacerbate neurotoxicity of PFAS. While limitations and inconsistencies across studies exist, the available body of evidence suggests that the neurobehavioral impacts of long-chain PFAS exposures during development are more pronounced than impacts resulting from exposure during adulthood. There is a paucity of experimental studies evaluating neurobehavioral and molecular mechanisms of short-chain PFAS, and even greater data gaps in the analysis of neurotoxicity for PFAS outside of the perfluoroalkyl acids. Whereas most experimental studies were focused on acute and subchronic impacts resulting from high dose exposures to a single PFAS congener, more realistic exposures for humans and wildlife are mixtures exposures that are relatively chronic and low dose in nature. Our evaluation of the available human epidemiological, experimental, and wildlife data also indicates heightened accumulation of perfluoroalkyl acids in the brain after environmental exposure, in comparison to the experimental studies. These findings highlight the need for additional experimental analysis of neurodevelopmental impacts of environmentally relevant concentrations and complex mixtures of PFAS.

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Section: Pfas Uptake and Accumulation In The Brainmentioning

confidence: 99%

Section: Neurotoxic Effects Of Co-exposures and Mixtures Of Pfasmentioning

confidence: 99%

Section: Neurotoxic Effects Of Co-exposures and Mixtures Of Pfasmentioning

confidence: 99%

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A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

et al. 2022

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“…Exposure concentrations for PFOS ranged from 0 to 500 mg/L and from 0 to 2000 mg/L for PFOA and PFHxS. We did not analyze water concentrations because previous experiments from our research group have demonstrated limited degradation of these PFAS under experimental conditions (Hoover et al 2017; Abercrombie et al 2019) and have demonstrated that actual concentrations were very close to nominal concentrations (Foguth et al 2020).…”

Section: Methodsmentioning

confidence: 99%

Relative acute toxicity of three per‐ and polyfluoroalkyl substances on nine species of larval amphibians

Tornabene

Chislock

Gannon

et al. 2021

Integr Envir Assess & Manag

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Per‐ and polyfluoroalkyl substances (PFAS) are widespread, persistent environmental pollutants known to elicit a wide range of negative effects on wildlife species. There is scarce information regarding the toxicity of PFAS on amphibians, but amphibians may be highly susceptible because of their permeable skin and dependence on fresh water. Acute toxicity studies are a first step toward understanding responses to PFAS exposure, providing benchmarks for species‐specific tolerances, informing ecological risk assessment (ERA), and designing chronic toxicity studies. We conducted standardized 96‐h lethal concentration (LC50) toxicity tests for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) with 9 widely distributed amphibian species native to eastern and central North America. We also conducted LC50 tests with perfluorohexane sulfonate (PFHxS) for 2 species and determined whether toxicity of PFOS and PFOA varied between life stages for 3 species. Acute toxicity varied among PFAS and species and between developmental stages within species. Across all species, toxicity of PFOS was more than 8× higher than PFOA. Salamanders in the genus Ambystoma were generally more sensitive to PFOS than were anurans (frogs and a toad). Toxicity of PFOA was highest for small‐mouthed salamanders and gray tree frogs and lowest for Jefferson salamanders, American bullfrogs, green frogs, and wood frogs. Although only 2 species were exposed to PFHxS, survival was lower for green frogs than for American bullfrogs. Toxicity of PFAS also varied between developmental stages of larvae. Gray tree frogs were more sensitive at later developmental stages, and small‐mouthed salamanders were more sensitive at earlier developmental stages. Our study is one of the first to report species‐, developmental stage‐, and compound‐specific differences in sensitivity to PFAS across a wide range of amphibian species. The benchmarks for toxicity we determined can inform conservation and remediation efforts, guide chronic toxicity studies, and help predict influences on amphibian communities, thereby informing future ERAs for PFAS. Integr Environ Assess Manag 2021;17:684–689. © 2021 SETAC

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“…Per-and poly uoroalkyl substances (PFAS) are emerging contaminants which have been used in a wide range of manufacturing including semiconductors, coatings for paper food packaging and textiles, and aqueous re-ghting foams (AFFF) (Prevedouros et al, 2006;Renner, 2001;Domingo et al, 2017;Martin et al, 2019;Langberg et al, 2020;Glüge et al, 2020;Wu et al, 2020). Because of their strong carbon and uorine bonds and hydrophilic and lipophilic characteristics, they are extremely persistent, thermal and chemical durable as well as bioaccumulative (Buck et al, 2011;Niu et al, 2019;Foguth et al, 2020;Stoiber et al, 2020). In a differentiation of PFAS, per uorooctane sulfonate (PFOS) and per uorooctanoic acid (PFOA) have been under continual investigation globally in the environment, animal tissues, and human blood (Giesy & Kannan, 2001;Kannan et al, 2004;Jantzen et al, 2016;Olsen et al, 2017;Awad et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Per- and polyfluoroalkyl substances in groundwater of Thailand: Occurrence, source identification and spatial distribution

Hongkachok¹,

Boontanon²,

Boontanon³

et al. 2021

Preprint

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Per- and polyfluoroalkyl (PFAS) have the potential to leach down to the groundwater particularly in areas with potential source pollution such as landfills. The composition patterns of PFAS, distribution and soil characteristics significantly contribute to their source identification. The objectives of this study were: (1) to examine the levels of PFAS in Thailand groundwater, (2) to identify potential sources, and (3) to study the spatial distribution of PFAS. Groundwater samples were collected around municipal waste disposal sites (MWDS) and industrial waste disposal sites (IWDS). Seven PFAS were extracted by solid phase extraction technique and analyzed by high-performance liquid chromatography tandem mass spectrometer. Total PFAS in groundwater around the MWDSs varied from 1.68 to 7.75 ng L− 1. The total PFAS in groundwater around the IWDS varied from 2.64 to 42.01 ng L− 1. PFOA and PFOS were the most dominant compounds around the MWDS and IWDS areas. PFHxS was frequently observed in the groundwater around the IWDSs, suggesting that it has been used as a substitution of PFOS-based compounds due to it having a shorter chain length or resulting from degradation of fluorotelomers. In addition to source identification, the hierarchical cluster analysis showed that other than the waste disposal site, other factors or activities could have been involved. It was found that livestock farming and an abandoned pond very close to the groundwater well could have affected the levels of PFAS in the groundwater. Moreover, spatial distribution showed that besides the impact of waste sources, soil characteristics and interaction between negative charged PFAS and cation in the soil played an important role in the PFAS contamination in groundwater.

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Single and mixture per- and polyfluoroalkyl substances accumulate in developing Northern leopard frog brains and produce complex neurotransmission alterations

Cited by 37 publications

References 42 publications

A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior

Relative acute toxicity of three per‐ and polyfluoroalkyl substances on nine species of larval amphibians

Per- and polyfluoroalkyl substances in groundwater of Thailand: Occurrence, source identification and spatial distribution

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