NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Carboxylates (Perfluorohexanoic Acid, Perfluorooctanoic Acid, Perfluorononanoic Acid, and Perfluorodecanoic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

,

doi:10.22427/ntp-tox-97

Cited by 11 publications

(3 citation statements)

References 93 publications

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“…In general, male rats appear more sensitive to PFAS-induced liver toxicity in comparison with females and show more severe liver pathology in comparison with females at equipotent doses. 94 , 97 , 99 , 100 These findings support the selection of male rat toxicity data for derivation of RPFs. The database may be found in Table S1.…”

Section: Methodssupporting

confidence: 57%

“…For seven PFAS (PFHxA, PFOA, PFNA, PFDA, PFBS, PFHxS, PFOS), measured serum concentrations were available to verify the performance of the models to simulate the serum concentrations after repeated dosing. Verification was done by plotting modeled serum concentrations together with empirically obtained repeated-dose serum concentrations obtained after daily exposure for 28 d. 99 , 100 These serum concentration data were retrieved from the CEBS database as well. Furthermore, the ratio between the modeled and reported mean serum concentration at the end of the study was evaluated.…”

Section: Methodsmentioning

confidence: 99%

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Internal Relative Potency Factors for the Risk Assessment of Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) in Human Biomonitoring

Bil

Zeilmaker

Bokkers

2022

Environ Health Perspect

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Background: In human biomonitoring, blood is often used as a matrix to measure exposure to per- and polyfluoroalkyl substances (PFAS). Because the toxicokinetics of a substance (determining the steady-state blood concentration) may affect the toxic potency, the difference in toxicokinetics among PFAS has to be accounted for when blood concentrations are used in mixture risk assessment. Objectives: This research focuses on deriving relative potency factors (RPFs) at the blood serum level. These RPFs can be applied to PFAS concentrations in human blood, thereby facilitating mixture risk assessment with primary input from human biomonitoring studies. Methods: Toxicokinetic models are generated for 10 PFAS to estimate the internal exposure in the male rat at the blood serum level over time. By applying dose–response modeling, these internal exposures are used to derive quantitative internal RPFs based on liver effects. Results: Internal RPFs were successfully obtained for nine PFAS. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoDA), perfluorooctane sulfonic acid (PFOS), and hexafluoropropylene oxide-dimer acid (HFPO-DA, or GenX) were found to be more potent than perfluorooctanoic acid (PFOA) at the blood serum level in terms of relative liver weight increase, whereas perfluorobutane sulfonic acid (PFBS) and perfluorohexane sulfonic acid (PFHxS) were found to be less potent. The practical implementation of these internal RPFs is illustrated using the National Health and Nutrition Examination Survey (NHANES) biomonitoring data of 2017–2018. Discussion: It is recommended to assess the health risk resulting from exposure to PFAS as combined, aggregate exposure to the extent feasible. https://doi.org/10.1289/EHP10009

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Section: Methodssupporting

confidence: 57%

Section: Methodsmentioning

confidence: 99%

Internal Relative Potency Factors for the Risk Assessment of Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) in Human Biomonitoring

Bil

Zeilmaker

Bokkers

2022

Environ Health Perspect

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“…However, breaking a C-C bond is less effective than C-F bond cleavage, 16,17 since the former generates short-chain perfluoroalkyl substances that are still found to be toxic. 18,19 Thus, the primary challenge in the complete treatment of PFAScontaminated water is the efficient dissociation of the strong C-F bonds in these pollutants.…”

mentioning

confidence: 99%

Real-time degradation dynamics of hydrated per- and polyfluoroalkyl substances (PFASs) in the presence of excess electrons

Yamijala

Shinde

Wong

2020

Phys. Chem. Chem. Phys.

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Deciphering the Mechanistic Basis for Perfluoroalkyl‐Protein Interactions

et al. 2023

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Although rarely used in nature, fluorine has emerged as an important elemental ingredient in the design of proteins with altered folding, stability, oligomerization propensities, and bioactivity. Adding to the molecular modification toolbox, here we report the ability of privileged perfluorinated amphiphiles to noncovalently decorate proteins to alter their conformational plasticity and potentiate their dispersion into fluorous phases. Employing a complementary suite of biophysical, in‐silico and in‐vitro approaches, we establish structure‐activity relationships defining these phenomena and investigate their impact on protein structural dynamics and intracellular trafficking. Notably, we show that the lead compound, perfluorononanoic acid, is 106 times more potent in inducing non‐native protein secondary structure in select proteins than is the well‐known helix inducer trifluoroethanol, and also significantly enhances the cellular uptake of complexed proteins. These findings could advance the rational design of fluorinated proteins, inform on potential modes of toxicity for perfluoroalkyl substances, and guide the development of fluorine‐modified biologics with desirable functional properties for drug discovery and delivery applications.

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NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Carboxylates (Perfluorohexanoic Acid, Perfluorooctanoic Acid, Perfluorononanoic Acid, and Perfluorodecanoic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

Cited by 11 publications

References 93 publications

Internal Relative Potency Factors for the Risk Assessment of Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) in Human Biomonitoring

Internal Relative Potency Factors for the Risk Assessment of Mixtures of Per- and Polyfluoroalkyl Substances (PFAS) in Human Biomonitoring

Real-time degradation dynamics of hydrated per- and polyfluoroalkyl substances (PFASs) in the presence of excess electrons

Deciphering the Mechanistic Basis for Perfluoroalkyl‐Protein Interactions

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