Toxicokinetics of perfluorobutane sulfonate (PFBS), perfluorohexane-1-sulphonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in male and female Hsd:Sprague Dawley SD rats after intravenous and gavage administration

Huang, Madelyn C.; Dzierlenga, Anika L.; Robinson, Victor A.; Waidyanatha, Suramya; DeVito, Michael J.; Eifrid, M.A.; Granville, Courtney A.; Gibbs, Seth; Blystone, Chad R.

doi:10.1016/j.toxrep.2019.06.016

Cited by 50 publications

(47 citation statements)

References 37 publications

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“…A similar half-life was observed in males after intravenous administration (4.5 hours), whereas females displayed a shorter half-life comparatively (4.0 hours) 33 . These half-lives are consistent with short half-lives reported in Huang et al 31 studies in Sprague Dawley rats (~5 hours in males, ~2 hours in females across multiple doses). An intravenous dose of 10 mg/kg potassium PFBS in cynomolgus monkeys demonstrated gamma half-lives of 11.3 hours in males and 83.2 hours in females, respectively.…”

Section: Absorption Distribution Metabolism Excretion and Toxicoksupporting

confidence: 90%

“…Kinetics studies demonstrated half-lives of about 40 days in Sprague Dawley male rats, 60 to 70 days in female rats, and 30 to 40 days in CD-1 male and female mice after a single oral administration of 2 or 15 mg/kg in rats and 1 or 20 mg/kg in mice 37 . Huang et al 31 studies in Hsd:Sprague Dawley SD rats showed a half-life of about 38 days in male and female rats after gavage administration of 2 or 20 mg/kg. In cynomolgus monkeys, half-lives of 132 days in males and 110 days in females were observed after intravenous administration 37 .…”

Section: Pfosmentioning

confidence: 99%

“…Physiologically based pharmacokinetic (PBPK) modeling of PFAS has included a saturable renal resorption function [24][25][26][27][28][29] . The pharmacokinetic properties were evaluated for several PFAS in the Hsd:Sprague Dawley rat, the animal model used in these 28-day toxicity studies [30][31][32] .…”

Section: Absorption Distribution Metabolism Excretion and Toxicokmentioning

confidence: 99%

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NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Sulfonates (Perfluorobutane Sulfonic Acid, Perfluorohexane Sulfonate Potassium Salt, and Perfluorooctane Sulfonic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

2019

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Section: Absorption Distribution Metabolism Excretion and Toxicoksupporting

confidence: 90%

Section: Pfosmentioning

confidence: 99%

Section: Absorption Distribution Metabolism Excretion and Toxicokmentioning

confidence: 99%

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NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Sulfonates (Perfluorobutane Sulfonic Acid, Perfluorohexane Sulfonate Potassium Salt, and Perfluorooctane Sulfonic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

2019

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“…Huang et al. (2019a) investigated the toxicokinetics of PFBS in male and female Sprague‐Dawley rats. After a single i.v.…”

Section: Appendix C– Toxicokinetics In Experimental Animalsmentioning

confidence: 99%

“…The NTP study showed that in male and female Sprague‐Dawley rats administered once daily by gavage, for 28 days, to PFOS doses from 0.312 to 5 mg/kg bw per day, plasma concentrations were similar in males and females and the liver/plasma ratios (measured in males only) ranged from 2.7 to 3.8 (NTP, 2019b). After a single gavage administration of 2 mg/kg PFOS to male and female Sprague‐Dawley rats, Huang and co‐workers found a liver/plasma ratio of 3–4 in females, whereas in males, the ratio increased from ca 5 (1 day post‐dose) to 30 (140 days post‐dose); a half‐life of about 38 days was calculated in both sexes (Huang et al., 2019a). Table C.2 summarises selected TK parameters for PFOS.…”

Section: Appendix C– Toxicokinetics In Experimental Animalsmentioning

confidence: 99%

Risk to human health related to the presence of perfluoroalkyl substances in food

Schrenk¹,

Bignami²,

Bodin³

et al. 2020

EFS2

307

265

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The European Commission asked EFSA for a scientific evaluation on the risks to human health related to the presence of perfluoroalkyl substances ( PFAS s) in food. Based on several similar effects in animals, toxicokinetics and observed concentrations in human blood, the CONTAM Panel decided to perform the assessment for the sum of four PFAS s: PFOA , PFNA , PFH xS and PFOS . These made up half of the lower bound ( LB ) exposure to those PFAS s with available occurrence data, the remaining contribution being primarily from PFAS s with short half‐lives. Equal potencies were assumed for the four PFAS s included in the assessment. The mean LB exposure in adolescents and adult age groups ranged from 3 to 22, the 95th percentile from 9 to 70 ng/kg body weight (bw) per week. Toddlers and ‘other children’ showed a twofold higher exposure. Upper bound exposure was 4‐ to 49‐fold higher than LB levels, but the latter were considered more reliable. ‘Fish meat’, ‘Fruit and fruit products’ and ‘Eggs and egg products’ contributed most to the exposure. Based on available studies in animals and humans, effects on the immune system were considered the most critical for the risk assessment. From a human study, a lowest BMDL 10 of 17.5 ng/ mL for the sum of the four PFAS s in serum was identified for 1‐year‐old children. Using PBPK modelling, this serum level of 17.5 ng/ mL in children was estimated to correspond to long‐term maternal exposure of 0.63 ng/kg bw per day. Since accumulation over time is important, a tolerable weekly intake ( TWI ) of 4.4 ng/kg bw per week was established. This TWI also protects against other potential adverse effects observed in humans. Based on the estimated LB exposure, but also reported serum levels, the CONTAM Panel concluded that parts of the European population exceed this TWI , which is of concern.

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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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Toxicokinetics of perfluorobutane sulfonate (PFBS), perfluorohexane-1-sulphonic acid (PFHxS), and perfluorooctane sulfonic acid (PFOS) in male and female Hsd:Sprague Dawley SD rats after intravenous and gavage administration

Abstract: Graphical abstract

Cited by 50 publications

References 37 publications

NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Sulfonates (Perfluorobutane Sulfonic Acid, Perfluorohexane Sulfonate Potassium Salt, and Perfluorooctane Sulfonic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Sulfonates (Perfluorobutane Sulfonic Acid, Perfluorohexane Sulfonate Potassium Salt, and Perfluorooctane Sulfonic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats

Risk to human health related to the presence of perfluoroalkyl substances in food

Deciphering the Mechanistic Basis for Perfluoroalkyl‐Protein Interactions

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