Isomer-Specific Biotransformation of Perfluorooctane Sulfonamide in Sprague–Dawley Rats

Abstract

Great variability exists in perfluorooctane sulfonate (PFOS) isomer patterns in human and wildlife samples, including unexpectedly high percentages (e.g., >40%) of branched isomers in human sera. Previous in vitro tests showed that branched PFOS-precursors were biotransformed faster than the corresponding linear isomer. Thus, high percentages of branched PFOS may be a biomarker of PFOS-precursor exposure in humans. We evaluated this hypothesis by examining the isomer-specific fate of perfluorooctane sulfonamide (PFOSA), a known PFOS-precursor, in male Sprague-Dawley rats exposed to commercial PFOSA via food for 77 days (83.0 ± 20.4 ng kg(-1) day(-1)), followed by 27 days of depuration. Elimination half-lives of the two major branched PFOSA isomers (2.5 ± 1.0 days and 3.7 ± 1.2 days) were quicker than for linear PFOSA (5.9 ± 4.6 days), resulting in a depletion of branched PFOSA isomers in blood and tissues relative to the dose. A corresponding increase in the total branched isomer content of PFOS, the ultimate metabolite, in rat serum was not observed. However, a significant enrichment of 5m-PFOS and a significant depletion of 1m-PFOS were observed, relative to authentic electrochemical PFOS. The data cannot be directly extrapolated to humans, due to known differences in the toxicokinetics of PFOS in rodents and humans. However, the results confirm that in vivo exposure to commercially relevant PFOS-precursors can result in a distinct PFOS isomer profile that may be useful as a biomarker of exposure source.

Temporal changes (1997–2012) of perfluoroalkyl acids and selected precursors (including isomers) in Swedish human serum

“…1), is in line with the trends observed in food. This trend could also (partly) be explained by shorter disappearance half-lives of branched isomers compared to the linear isomer (Table 1), which could be the result of faster biotransformation of branched isomers to branched PFOS relative to the linear isomer (Benskin et al, 2009;Ross et al, 2012). Faster urinary elimination of linear precursors relative to branched precursors, as was observed in humans (Zhang et al, 2013a), would, on the other hand, result in increasing relative importance of branched precursor isomers over time.…”

Perfluorooctane sulfonate: A review of human exposure, biomonitoring and the environmental forensics utility of its chirality and isomer distribution

“…Current evidence to support this hypothesis is not clear-cut however (Ross et al, 2012). While excretion in rats of branched chain PFOSAs exceeded that of the linear isomer; a corresponding increase in the relative abundance of the sum of branched chain PFOS isomers was not observed in the same animals.…”

“…More detailed analysis of the relative abundance of individual branched chain isomers in this study suggests a more complex situation. While the relative abundance in the studied rats of one branched isomer (5 m-PFOS), increased relative to its abundance in a commercial PFOS mixture; that of another (1 m-PFOS) decreased (Ross et al, 2012). This may point to a need to monitor relative abundances of individual branched chain isomers rather than the sum of all such isomers, to provide more conclusive insights into the relative contribution of precursor exposure.…”

“…The POSF-derived substances in question represent a vast array of structures with the general formula C 8 F 17 SO 2 NRR′, that are referred to generically as "PFOS-precursors" (or "PreFOS" in some literature, such as Asher et al, 2012). Consequently, as described by Prevedouros et al (2006), and Ross et al (2012), two general routes of exposure may occur: (1) direct exposure to PFOS, through diet, inhalation, and contact with contaminated settled dust (either by ingestion or dermal contact), and (2) exposure to PFOS-precursors, followed by their biotransformation in the body to PFOS. The main PFOSprecursor substances and its salts are listed in Table 6.…”

Temporal trends of perfluorooctanesulfonate isomer and enantiomer patterns in archived Swedish and American serum samples

“…Commercially relevant batches of PreFOS were also~30% branched (Korkowski and Kestner, 1999;Reagen et al, 2008), and studies have shown the preferential excretion of linear PreFOS (i.e. perfluorooctanesulfonamide (FOSA)) compared to branched PreFOS through urine in rodents (Ross et al, 2012) and in humans (Zhang et al, 2013a), resulting in preferential retention of branched FOSA isomers that can then be biotransformed to branched PFOS. Moreover, branched PreFOS isomers are metabolized faster than linear PreFOS in vitro by human liver microsomes (Benskin et al, 2009b) and in vivo in rats (Benskin et al, 2009a).…”