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The study reviews the current state of knowledge regarding the biotransformation of fluorotelomer-based compounds, with a focus on compounds that ultimately degrade to form perfluoroalkyl carboxylates (PFCAs). Most metabolism studies have been performed with either microbial systems or rats and mice, and comparatively few studies have used fish models. Furthermore, biotransformation studies thus far have predominately used the 8:2 fluorotelomer alcohol (FTOH) as the substrate. However, there have been an increasing number of studies investigating 6:2 FTOH biotransformation as a result of industry's transition to shorter-chain fluorotelomer chemistry. Studies with the 8:2 FTOH metabolism universally show the formation of perfluorooctanoate (PFOA) and, to a smaller fraction, perfluorononanoate (PFNA) and lower-chain-length PFCAs. In general, the overall yield of PFOA is low, presumably because of the multiple branches in the biotransformation pathways, including conjugation reactions in animal systems. There have been a few studies of non-FTOH biotransformation, which include polyfluoroalkyl phosphates (PAPs), 8:2 fluorotelomer acrylate (8:2 FTAC), and fluorotelomer carboxylates (FTCAs, FTUCAs). The PAPs compounds and 8:2 FTAC were shown to be direct precursors to FTOHs and thus follow similar degradation pathways. Environ Toxicol Chem 2014;33:243-267. © 2013 SETAC [ABSTRACT FROM AUTHOR]

Many halogenated organic contaminants(HOCs) are considered endocrinedisruptors and affect the hypothalamic–pituitary–thyroidaxis, often by interfering with circulating levels of thyroid hormones(THs). We investigated one potential mechanism for TH disruption,inhibition of sulfotransferase activity. One of the primary rolesof TH sulfation is to support the regulation of biologically activeT3 through the formation of inactive THs. We investigated TH sulfotransferaseinhibition by 14 hydroxylated polybrominated diphenyl ethers (OH BDEs),BDE 47, triclosan, and fluorinated, chlorinated, brominated, and iodinatedanalogues of 2,4,6-trihalogenated phenol and bisphenol A (BPA). Anew mass spectrometry-based method was also developed to measure theformation rates of 3,3′-T2 sulfate (3,3′-T2S). Usingpooled human liver cytosol, we investigated the influence of theseHOCs on the sulfation of 3,3′-T2, a major substrate for THsulfation. For the formation of 3,3′-T2S, the Michaelis constant(Km) was 1070 ± 120 nM and the Vmaxwas 153 ± 6.6 pmol min–1(mg of protein)−1. All chemicals investigatedinhibited sulfotransferase activity with the exception of BDE 47.The 2,4,6-trihalogenated phenols were the most potent inhibitors followedby the OH BDEs and then halogenated BPAs. The IC50valuesfor the OH BDEs were primarily in the low nanomolar range, which maybe environmentally relevant. In silicomolecularmodeling techniques were also used to simulate the binding of OH BDEto SULT1A1. This study suggests that some HOCs, including antimicrobialchemicals and metabolites of flame retardants, may interfere withTH regulation through inhibition of sulfotransferase activity. [ABSTRACT FROM AUTHOR]

Temporal trends in perfluoroalkyl compounds (PFCs) were investigated in liver samples from two seabird species, thick-billed murres (Uria lomvia) and northern fulmars (Fulmaris glacialis), from Prince Leopold Island in the Canadian Arctic. Thick-billed murre samples were from 1975, 1993, and 2004, whereas northern fulmars were from 1975, 1987, 1993, and 2003. Between 8 and 10 individuals were analyzed per year. Analytes included C7-C15 perfluorinated carboxylates (PFCAs) and their suspected precursors, the 8:2 & 10:2 fluorotelomer saturated and unsaturated carboxylates (FTCAs, FTUCAs), C6, C8 (perfluorooctane sulfonate, PFOS), C10 sulfonates, and perfluorooctane sulfonamide (PFOSA). Liver samples were homogenized, liquid-liquid extracted with methyl tert-butyl ether, cleaned-up using hexafluoropropanol, and analyzed by LC-MS/MS. Overall, concentrations in seabirds were lower than those in other marine animals that occupy similar or higher trophic positions. In contrast to most other wildlife samples, PFC profiles were dominated by the PFCAs which comprised 81% and 93% of total PFC profiles in the 2004 thick-billed murre and 2003 northern fulmar samples, respectively. As well, the PFCA profiles were mainly comprised of the C11-C15 PFCAs, which appears to be unique among other wildlife species. PFC concentrations were found to increase significantly from 1975 to 2003/2004. Doubling times in thick-billed murres ranged from 2.3 yrs for perfluoropentadecanoate (PFPA) to 9.9 yrs for perfluorododecanoate (PFDoA), and from 2.5 yrs for PFPA to 11.7 yrs for perfluorodecanoate (PFDA) in northern fulmars. PFCA concentration increases in thick-billed murres were significant for both time periods (1975→1993, 1993→2004), but in northern fulmars appeared to remain steady after 1993. Differences in the temporal trends observed may be the result of differing migratory patterns of the seabirds. Finally, the detection of the 8:2 and 10:2 FTUCAs in seabirds is suggestive of fluorotelomer alcohols as a source of some PFCAs. [ABSTRACT FROM AUTHOR]

Temporal trends in perfluoroalkyl compounds (PFCs) were investigated in liver samples from two ringed seal (Phoca hispida) populations in the Canadian Arctic, Arviat (Western Hudson Bay) (1992, 1998, 2004, 2005) and Resolute Bay (Lancaster Sound) (1972, 1993, 2000, 2004, 2005). PFCs analyzed included C7–C15 perfluorinated carboxylates (PFCAs) and their suspected precursors, the 8:2 and 10:2 fluorotelomer saturated and unsaturated carboxylates (FTCAs, FTUCAs), C4, C6, C8, C10 sulfonates, and perfluorooctane sulfonamide (PFOSA). Liver samples were homogenized, liquid-liquid extracted with methyl tert-butyl ether, cleaned up using hexafluoropropanol, and analyzed by liquid chromatography with negative electrospray tandem mass spectrometry (LC-MS/MS). C9–C15 PFCAs showed statistically significant increasing conàentrations during 1992–2005 and during 1993–2005 at Arviat and Resolute Bay, respectively. Doubling times ranged from 19.4 to 15.8 years for periluorododecanoate (PFOSA) to 10.0–7.7 years for perfluorononanoate (PFNA) at Arviat and Resolute Bay but were shorter when excluding the 2005 samples. Conversely, periluorooctane sulfonate (PFOS) and PFOSA concentra- tions showed maximum concentrations during 1998 and 2000 at Arviat and Resolute Bay, with statistically significant decreases from 2000 to 2005. In the case of Arviat, two consecutive decreases were measured from 1998 to 2003 and from 2003 to 2005. PFOS disappearance half-lives for seals at Arviat and Resolute Bay were 3.2 and 4.6 years. These results indicate that the ringed seals and their food web are rapidly responding to the phase out of pertluorooctane sulfonyl fluoride based compounds by 3M in 2001. Further, the relatively short doubling times of the PFCAs and PFOS disappearance half-lives support the hypothesis of atmospheric transport as the main transport mechanism of PFCs to the arctic environment. [ABSTRACT FROM AUTHOR]

Organic films were collected from indoor and outdoor window surfaces, along an urban--rural transect extending northward from Toronto, Ontario, Canada, and analyzed for 41 polybrominated diphenyl ether congeners (PBDE). For exterior films, urban ΣPBDE concentrations were ∼10× greater than rural concentrations, indicating an urban--rural gradient and greater PBDE sources in urban areas. Urban films ranged from 2.5 to 14.5 ng/m[sup2] (mean = 9.0 ng/ m[sup2]), excluding the regional "hotspot" Electronics Recycling Facility, compared to 1.1 and 0.56 ng/m[sup2] at the Suburban and Rural sites. Interior urban films (mean = 34.4 ng/m[sup2]) were 3 times greater than rural films (10.3 ng/m[sup2]) and were representative of variations in building characteristics. Indoor films were 1.5-20 times greater than outdoor films, consistent with indoor sources of PBDEs and enhanced degradation in outdoor films. Congener profiles were dominated by BDE-209 (51.1%), consistent with deca-BDE as the main source mixture, followed by congeners from the penta-BDE mixture (BDE-99:13.6% and -47:9.4%) and some octa-BDE (BDE-183:1.5%). Congener patterns suggest a degradative loss of lower brominated compounds in outdoor films versus indoor films. Gas-phase air concentrations were back-calculated from film concentrations using the film--air partition coefficient (K[subFA]). Mean calculated air concentrations were 4.8 pg/m[sup3] for outdoor and 42.1 pg/m[sup3] for indoor urban sites, indicating that urban indoor air is a source of PBDEs to urban outdoor air and the outdoor regional environment. [ABSTRACT FROM AUTHOR]

The biotransformation of fluorotelomer based compounds yields saturated and unsaturated fluorotelomer aldehydes (FTALs and FTUALs, respectively) and carboxylic acids (FTCAs and FTUCAs, respectively) as intermediate metabolites that subsequently transform to perfluorinated carboxylic acids (PFCAs). Previous studies have demonstrated that the FTCAs and FTUCAs are 1 to 5 orders of magnitude more toxic than PFCAs after exposure to aquatic organisms. Additionally, FTUALs have demonstrated reactivity with proteins, which may be associated with toxicity through the inhibition of protein function. The purpose of this study was to carry out a comprehensive assessment of the relative toxicity between PFCAs and their intermediate precursor metabolites: the FTALs, FTUALs, FTCAs, and FTUCAs. Analytes were separately incubated with human liver epithelial (THLE-2) cells to assess how varying the functional group and the fluorinated chain length affects cell viability. For each analyte, dose-response EC50 values were calculated. The EC50 values for FTUCAs and FTCAs were similar, with values ranging from 22 ± 9 and 24 ± 9 μM for the 10:2 congeners to 1004 ± 20 and 1004 ± 24 μM for the 4:2 congeners, respectively. The EC50 values for the PFCAs ranged from 65 ± 41 (PFDA) to 1361 ± 146 (PFBA) μM. The range of toxicity between PFCAs and their acid precursors were similar. However, the comparative toxicity between the 6:2 and 8:2 congeners and their corresponding PFCA had toxicity thresholds that varied depending on the functional headgroup, where FTUALs ≥ FTALs > FTUCAs ≥ FTCAs > PFCAs. For all PFCAs and acid precursors, toxicity depended on the length of the fluorinated chain, where the longer chain lengths yielded greater bioaccumulation and enhanced toxicity, results which agreed with those previously reported. By contrast, FTALs and FTUALs were the most toxic of all the analytes examined, where toxicity was enhanced at shorter chain lengths, with EC50 values of 7 ± 1 μM (6:2 FTUAL) and 8.6 ± 0.8 μM (6:2 FTAL). DNA adducts were not detectable for the aldehyde precursors, using a quantitative long-range PCR method. Our data provide the first evidence that aldehyde intermediates have demonstrated toxicity in cellular systems that is more significant than PFCAs and their corresponding acid intermediates.