Disposition of perfluorinated acid isomers in sprague‐dawley rats; Part 2: Subchronic dose

Abstract

Two major industrial synthetic pathways have been used to produce perfluorinated acids (PFAs) or their precursors: Telomerization and electrochemical fluorination (ECF). Products of telomer and ECF origin can be distinguished by structural isomer profiles. A mixture of linear and branched perfluoroalkyl isomers is associated with ECF. Telomer products characteristically consist of a single perfluoroalkyl geometry, typically linear. In biota, it is unclear if the isomer profile is conserved relative to the exposure medium and hence whether PFA isomer profiles in organisms are useful for distinguishing environmental PFA sources. A companion study suggested isomer-specific disposition following a single oral gavage exposure to rats. To confirm these findings under a more realistic subchronic feeding scenario, male and female rats were administered PFA isomers by diet for 12 weeks, followed by a 12-week depuration period. The diet contained 500 ng/g each of ECF perfluorooctanoate (PFOA, approximately 80% n-PFOA), ECF perfluorooctane sulfonate (PFOS, approximately 70% n-PFOS), and linear and isopropyl perfluorononanoate (n- and iso-PFNA). Blood sampling during the exposure phase revealed preferential accumulation of n-PFOA and n-PFNA compared to most branched isomers. Female rats depurated all isomers faster than males. Both sexes eliminated most branched perfluorocarboxylate isomers more rapidly than the n-isomer. Elimination rates of the major branched PFOS isomers were not statistically different from n-PFOS. Two minor isomers of ECF PFOA and one branched PFOS isomer had longer elimination half-lives than the n-isomers. Although extrapolation of these pharmacokinetics trends in rats to humans and wildlife requires careful consideration of dosage level and species-specific physiology, cumulative evidence suggests that perfluorocarboxylate isomer profiles in biota may not be suitable for quantifying the relative contributions of telomer and ECF sources.

Brain region distribution and patterns of bioaccumulative perfluoroalkyl carboxylates and sulfonates in East Greenland polar bears (Ursus maritimus)

“…Chem. 32,2013BBB than other brain regions, explaining the brain regionspecific accumulation patterns observed in this study.…”

“…Chem. 32,2013lipid content are likely between longer-chain PFCAs (C 10 -C 15 ) and nonpolar free fatty acids. The major fatty acids found in the brain are often between 12 and 26 carbons long, closely resembling the longer-chain PFCAs detected in the present study [29].…”

“…Due to the limited age trends observed, age was not considered to be a confounding factor of the PFAS concentrations among brain regions. The PFCAs and PFSAs have a large range of half-lives, from hours in rats and rabbits to years in humans and other larger mammals [31,32]. Although the half-lives of bioaccumulative PFCAs and PFSAs in polar bears have not been reported, these limited age correlations in the cerebellum and occipital cortex indicate halflives in the order of years for longer-chain PFCAs (C 10 -C 15 ), which suggests that they accumulate in the brain faster than they can be eliminated.…”

Perfluorooctane sulfonate toxicity, isomer‐specific accumulation, and maternal transfer in zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss)

“…Previous isomer-specific studies of PFCs in fish [18] and rats [19,20] have demonstrated that isomer profiles are conserved with this method. In brief, an average of 0.01 to 1.8 g of each trout tissue and 0.05 to 0.7 g of zebrafish egg or adult were homogenized using a mortar and pestle on dry ice and quantitatively transferred to 15-ml polypropylene centrifuge tubes (Corning).…”

“…Subsequent studies on the disposition of PFOA isomers in rainbow trout have indicated that n-PFOA is selectively retained in blood and tissues relative to the majority of branched isomers [18]. Similarly, rodents dosed with ECF mixtures of PFOA and PFOS selectively retained the linear isomer relative to most branched isomers [19,20], albeit kinetic differences between branched and linear isomers appear to be more subtle for PFOS than for PFOA and require further investigation in longer exposure studies. Biotransformation rates of PFOS-precursor isomers have also been observed in vitro [21], whereby branched isomers were preferentially biotransformed relative to the linear isomer.…”