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. 2019 Jun 28:6:645-655.
doi: 10.1016/j.toxrep.2019.06.016. eCollection 2019.

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

M C Huang  1 , A L Dzierlenga  1 , V G Robinson  1 , S Waidyanatha  1 , M J DeVito  1 , M A Eifrid  2 , C A Granville  2 , S T Gibbs  2 , C R Blystone  1
Affiliations

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

M C Huang et al. Toxicol Rep. .

Erratum in

Abstract

Perfluorinated alkyl substances (PFAS) are persistent contaminants that have been detected in the environment and in humans. With the PFAS chemical class, there are perfluorinated alkyl acids, many of which have been associated with certain toxicities. Because toxicity testing cannot feasibly be conducted for each individual PFAS, the National Toxicology Program (NTP) designed studies to compare toxicities across different subclasses of PFAS and across PFAS of different chain lengths to better understand the structure-toxicity relationship. Pharmacokinetic studies were conducted in parallel to these toxicity studies to facilitate comparisons across PFAS and to provide context for human relevance. Here, the toxicokinetic parameters of perfluorobutane sulfonate (PFBS), perfluorohexane-1-sulphonic acid (PFHxS), or perfluorooctane sulfonate (PFOS) after a single intravenous or gavage administration in male and female Hsd:Sprague-Dawley rats are reported. Concentrations of these PFAS were measured in the liver, kidney, and brain. Plasma half-life increased with longer chain length after gavage administration: PFBS- males averaged 3.3 h, females 1.3 h; PFHxS- males averaged 16.3 days, females 2.1 days; PFOS- males and females averaged ˜ 20 days. There were dose-dependent changes in clearance and systemic exposure for all administered chemicals and the direction of change was different in PFOS compared to the others. Liver:plasma ratios of PFOS were the highest followed by PFHxS and PFBS, while brain:plasma ratios were low in all three sulfonates. Sex differences in plasma half-life and tissue distribution were observed for PFBS and PFHxS, but not PFOS. These data provide a direct comparison of the kinetics of three different perfluoroalkyl sulfonic acids and allow for the contextualization of toxicity data in rats for human risk assessment of this chemical class.

Keywords: PFBS; PFHxS; PFOS; Perfluorinated alkyl acids; Perfluorinated chemicals; Rats; Toxicokinetics.

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Figures

None
Graphical abstract
Fig. 1
Fig. 1
Sulfonate perfluorinated alkyl acids evaluated: perfluorobutane sulfonate (PFBS), perfluorohexane-1-sulphonic acid (PFHxS), or perfluorooctane sulfonate (PFOS).
Fig. 2
Fig. 2
Plasma concentrations (nM; mean and SEM) of PFBS, PFHxS, or PFOS in male and female Hsd:Sprague-Dawley rats after a single administration of chemical. Three gavage and one iv dose were administered.
Fig. 3
Fig. 3
Tissue concentrations (nM; mean and SEM) and tissue:plasma ratios (mean and SEM) in male (A, C) and female (B, D) Hsd:Sprague-Dawley rats after a single gavage administration of KPFBS (20 mg/kg).
Fig. 4
Fig. 4
Tissue concentrations (nM; mean and SEM) and tissue:plasma ratios (mean and SEM) in male (A, C) and female (B, D) Hsd:Sprague-Dawley rats after a single gavage administration of PFHxSK (16 mg/kg).
Fig. 5
Fig. 5
Liver and kidney concentrations (nM; mean and SEM) in male and female Hsd:Sprague-Dawley rats after a single gavage administration of PFOS (2 or 20 mg/kg) or multiple administrations of PFOS (2 mg/kg/day for five days).
Fig. 6
Fig. 6
Tissue/plasma ratio (mean and SEM) for male and female Hsd:Sprague Dawley SD rats after a single gavage administration of PFOS (2 or 20 mg/kg) or multiple administrations of PFOS (2 mg/kg/day for five days).
Fig. 7
Fig. 7
Dose-adjusted area under the curve (AUC) of plasma concentrations vs. time of PFBS, PFHxS, or PFOS in male (A) and female (B) Hsd:Sprague-Dawley rats after a single gavage administration of chemical.
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