Sulfonamide functional head on short-chain perfluorinated substance drives developmental toxicity

Rericha, Yvonne; Cao, Dunping; Truong, Lisa; Simonich, Michael T.; Field, Jennifer A.; Tanguay, Robert L.

doi:10.1016/j.isci.2022.103789

Cited by 37 publications

(21 citation statements)

References 52 publications

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“…Federal and state regulatory efforts are presently focused on legacy PFAS predominantly detected in water and do not consider the full range of highly bioaccumulative terminal PFAA and precursors discussed in this work. Metabolism of precursors that exhibit a higher bioaccumulation potential than their terminal degradation products will enhance exposures to terminal PFAA of concern. , Some studies have suggested sulfonamide precursors have greater bioactivity than PFAA of similar perfluorinated carbon chain length due to their higher pKa, greater fraction of neutral species at similar pH, and interactions with lipids and membranes facilitated by the sulfonamide head group. ,− Additional physicochemical and toxicological data on diverse precursors, particularly the sulfonamides, are needed to better understand their bioaccumulation potential and toxicity. Our work suggests that more comprehensive fish advisories are needed to account for potential human exposures to the full suite of highly bioaccumulative longer-chain PFAA and ECF precursors.…”

Section: Discussionmentioning

confidence: 99%

“… 11 , 70 Some studies have suggested sulfonamide precursors have greater bioactivity than PFAA of similar perfluorinated carbon chain length due to their higher pKa, greater fraction of neutral species at similar pH, and interactions with lipids and membranes facilitated by the sulfonamide head group. 69 , 71 − 73 Additional physicochemical and toxicological data on diverse precursors, particularly the sulfonamides, are needed to better understand their bioaccumulation potential and toxicity. Our work suggests that more comprehensive fish advisories are needed to account for potential human exposures to the full suite of highly bioaccumulative longer-chain PFAA and ECF precursors.…”

Section: Discussionmentioning

confidence: 99%

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PFAS and Precursor Bioaccumulation in Freshwater Recreational Fish: Implications for Fish Advisories

Pickard¹,

Ruyle²,

Thackray³

et al. 2022

Environ. Sci. Technol.

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Per- and polyfluoroalkyl substances (PFAS) are a diverse class of fluorinated anthropogenic chemicals that include perfluoroalkyl acids (PFAA), which are widely used in modern commerce. Many products and environmental samples contain abundant precursors that can degrade into terminal PFAA associated with adverse health effects. Fish consumption is an important dietary exposure source for PFAS that bioaccumulate in food webs. However, little is known about bioaccumulation of PFAA precursors. Here, we identify and quantify PFAS in recreational fish species collected from surface waters across New Hampshire, US, using a toolbox of analytical methods. Targeted analysis of paired water and tissue samples suggests that many precursors below detection in water have a higher bioaccumulation potential than their terminal PFAA. Perfluorobutane sulfonamide (FBSA), a short-chain precursor produced by electrochemical fluorination, was detected in all fish samples analyzed for this compound. The total oxidizable precursor assay interpreted using Bayesian inference revealed fish muscle tissue contained additional, short-chain precursors in high concentration samples. Suspect screening analysis indicated these were perfluoroalkyl sulfonamide precursors with three and five perfluorinated carbons. Fish consumption advisories are primarily being developed for perfluorooctane sulfonate (PFOS), but this work reinforces the need for risk evaluations to consider additional bioaccumulative PFAS, including perfluoroalkyl sulfonamide precursors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PFAS and Precursor Bioaccumulation in Freshwater Recreational Fish: Implications for Fish Advisories

Pickard¹,

Ruyle²,

Thackray³

et al. 2022

Environ. Sci. Technol.

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“…Future studies with PFOS and 6:2 FTS can build upon this study by focusing on the dose range between 100 and 2000 μg/L (PFOS equivalents) to determine whether there is a predictable threshold effect within this range where the interaction shifts from less-than-additive to more-than-additive, and whether that threshold changes with ratios different from the approximate range 1:10–1:30 (PFOS to 6:2 FTS) examined in this study. In addition, concurrent evaluations of gene expression [ 33 , 34 ] would further elucidate potential modes of action that may explain the interactions observed with mixtures of PFOS and 6:2 FTS.…”

Section: Discussionmentioning

confidence: 99%

Is Mixtures’ Additivity Supported by Empirical Data? A Case Study of Developmental Toxicity of PFOS and 6:2 FTS in Wildtype Zebrafish Embryos

Goodrum

Razavi

Whipps

et al. 2022

Toxics

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Per- and polyfluoroalkyl substances (PFASs) are a major priority for many federal and state regulatory agencies charged with monitoring levels of emerging contaminants in environmental media and setting health-protective benchmarks to guide risk assessments. While screening levels and toxicity reference values have been developed for numerous individual PFAS compounds, there remain important data gaps regarding the mode of action for toxicity of PFAS mixtures. The present study aims to contribute whole-mixture toxicity data and advance the methods for evaluating mixtures of two key components of aqueous film-forming foams: perfluorooctanesulfonic acid (PFOS), and 6:2 fluorotelomer sulfonic acid (6:2 FTS). Wildtype (AB) zebrafish embryos were exposed to PFOS and 6:2 FTS, both as individual components and as binary mixtures, from 2 to 122 h post-fertilization. Five treatment levels were selected to encompass environmentally relevant exposure levels. Experimental endpoints consisted of mortality, hatching, and developmental endpoints, including swim bladder inflation, yolk sac area, and larval body length. Results from dose–response analysis indicate that the assumption of additivity using conventional points of departure (e.g., NOAEL, LOAEL) is not supported for critical effect endpoints with these PFAS mixtures, and that the interactions vary as a function of the dose range. Alternative methods for quantifying relative potency are proposed, and recommendations for additional investigations are provided to further advance assessments of the toxicity of PFAS mixtures to aquatic organisms.

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“…Other groups [ 15 , 16 ] have reported increased risks of autism spectrum disorder at age 3 with prenatal PFOA and PFNA exposures. Animal studies also support concerns for the neurodevelopmental risks posed by PFAS [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 94%

Predicting Exposure to Perfluorinated Alkyl Substances (PFAS) among US Infants

Kirk

Plasse

Kirk

et al. 2022

IJERPH

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PFASs have been detected in nearly every serum sample collected over the last two decades from US adults as part of the National Health and Nutrition Examination Survey (NHANES) and are commonly found in other data sets from around the world. However, less is known about infant PFAS exposures, primarily because the collection of infant serum samples is less common and frequently avoided. Cord blood samples are often preferred for chemical exposure assessments because this is thought to provide a good representation of infant serum concentrations, at least at the time of birth. In this paper, we will provide a statistical and probabilistic analysis of what can be expected for infants living in the US using NHANES from 2007 to 2008, which contains a rare subset of infant data. Regulatory efforts that require estimation of exposures among the very youth can be challenging, both because of a lack of data in general and because variability among this most vulnerable population can be uncertain. We report that US infant exposures are extremely common and that serum concentrations remain fairly constant, despite infant growth rates and relatively high caloric and fluid intake, with the possible exception of PFOS. Infant serum PFOS concentrations between months 1 and 3 are consistently higher than at less than one month, even though healthy infants at 1 and 2 months weigh more than they did at birth. This suggests that the babies are exposed to greater concentrations of PFOS after birth or that excretion kinetics differ for this PFAS.

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Sulfonamide functional head on short-chain perfluorinated substance drives developmental toxicity

Cited by 37 publications

References 52 publications

PFAS and Precursor Bioaccumulation in Freshwater Recreational Fish: Implications for Fish Advisories

PFAS and Precursor Bioaccumulation in Freshwater Recreational Fish: Implications for Fish Advisories

Is Mixtures’ Additivity Supported by Empirical Data? A Case Study of Developmental Toxicity of PFOS and 6:2 FTS in Wildtype Zebrafish Embryos

Predicting Exposure to Perfluorinated Alkyl Substances (PFAS) among US Infants

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