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Organophosphate esters (OPEs) are synthetic phosphoric acid derivatives used in a wide variety of applications including as flame retardants and plasticizers. Their production and usage has increased in recent years, due to the phase-out of other flame retardant formulations (e.g., polybrominated diphenyl ethers). As such, there has been a recent push to understand the global distribution of OPEs and their behaviour in biota. Multiple studies have been published over the last few years pertaining to OPE concentrations in biotic and abiotic environmental compartments, as well as the metabolism of OPEs in biota. This paper aims to provide a brief review of the occurrence and levels of OPEs in the environment, as well as recent developments concerning the elucidation of OPE metabolism in biota.

Perfluoroalkyl substances (PFASs) is a growing class of contaminants in the Arctic environment, and include the established perfluorinated sulfonates (PFSAs; especially perfluorooctane sulfonate (PFOS)) and carboxylic acids (PFCAs). PFSAs and PFCAs of varying chain length have been reported to bioaccumulate in lipid rich tissues of the brain among other tissues such as liver, and can reach high concentrations in top predators including the polar bear. PFCA and PFSA bioaccummulation in the brain has the potential to pose neurotoxic effects and therefore we conducted a study to investigate if variations in neurochemical transmitter systems i.e. the cholinergic, glutaminergic, dopaminergic and GABAergic, could be related to brain-specific bioaccumulation of PFASs in East Greenland polar bears. Nine brain regions from nine polar bears were analyzed for enzyme activity (monoamine oxidase (MAO), acetylcholinesterase (AChE) and glutamine synthetase (GS)) and receptor density (dopamine-2 (D2), muscarinic cholinergic (mAChR) and gamma-butyric acid type A (GABA-A)) along with PFSA and PFCA concentrations. Average brain ∑PFSA concentration was 25 ng/g ww where PFOS accounted for 91%. Average ∑PFCA concentration was 88 ng/g ww where PFUnDA, PFDoDA and PFTrDA combined accounted for 79%. The highest concentrations of PFASs were measured in brain stem, cerebellum and hippocampus. Correlative analyses were performed both across and within brain regions. Significant positive correlations were found between PFASs and MAO activity in occipital lobe (e.g. ∑PFCA; r p¼0.83, p¼0.041, n¼6) and across brain regions (e.g. ∑PFCA; rp¼0.47, p ¼0.001, ∑PFSA; rp¼0.44, p40.001; n¼50). GABA-A receptor density was positively correlated with two PFASs across brain regions (PFOS; rp ¼0.33, p¼0.02 and PFDoDA; rp ¼0.34, p ¼0.014; n¼52). Significant negative correlations were found between mAChR density and PFASs in cerebellum (e.g. ∑PFCA; rp ¼� 0.95, p¼0.013, n¼5) and across brain regions (e.g. ∑PFCA; rp ¼� 0.40, p¼0.003, ∑PFSA; rp ¼� 0.37, p ¼0.007; n¼52). AChE activity and D2 density were negatively correlated with single PFCAs in several brain regions, whereas GS activity was positively correlated with PFASs primarily in occipital lobe. Results from the present study support the hypothesis that PFAS concentrations in polar bears from East Greenland have exceeded the threshold limits for neurochemical alterations. It is not known whether the observed alterations in neurochemical signaling are currently having negative effects on neurochemistry in East Greenland polar bears. However given the importance of these systems in cognitive processes and motor function, the present results indicate an urgent need for a better understanding of neurochemical effects of PFAS exposure to wildlife.

Environmentally relevant organophosphate (OP) triester flame retardants are known to degrade to OP diester phosphoric acids. In this study, a quantitatively sensitive method was developed for OP diesters in biological samples of varying complexity, bovine serum, chicken egg homogenate and pork liver. Fortified with 1 ng or 10 ng each of the six OP diester and six OP triester standards, samples were extracted by accelerated solvent extraction that completely separated OP diesters and triesters. OP diester fractions were cleaned up using weak anion exchange solid phase extraction and eluted with high ionic strength ammonium acetate buffer. Optimal analysis of chlorinated OP diesters was via decamethonium hydroxide dicationic reagent derivatization and by LC-ESI(+)–MS/MS, and for all non-chlorinated OP diesters by non-derivatized LC-ESI(−)–MS/MS. Except for derivatization LC-ESI(+)–MS/MS analysis of liver, at the 10 ng spiking level for the three matrices, recovery efficiencies, matrix effects and method limits of quantification (MLOQs) of OP diesters ranged from 55–116%, 92–119%, and 0.02–0.31 ng/g wet weight (ww) respectively. Plasma samples of n = 6 herring gulls (2010, Chantry Is., Laurentian Great Lakes) contained triphenyl phosphate and tris(1-3-dichloro-2-propyl) phosphate ranging from 1.3 to 4.0 ng/g ww and

Although recent usage of organophosphate (OP) flame retardants has increased substantially, very few studies have reported on OPs in biota including wildlife, and essentially there is no information on OP body compartment composition and in ovo or in utero transfer for any given wildlife species. Concentrations and patterns of 16 OP triesters were presently screened for and/or determined in six body compartments from female herring gulls (Larus argentatus; n=8) and the separate egg yolk and albumen of their entire clutches of eggs (n=16) (collected in 2010 from a Lake Huron colony site, Laurentian Great Lakes of North America). Fat (32.3±9.8 ng/g wet weight; ww) contained the highest ΣOP concentration, followed by egg yolk (14.8±2.4 ng/g ww)≈egg albumen (14.8±5.9 ng/g ww)>muscle (10.9±5.1 ng/g ww)≫red blood cells (1.00±0.62 ng/g ww), whereas in liver, blood plasma, and brain all OPs were not detectable. Nine OPs accumulated in herring gulls, but the concentrations and proportions of OPs were dependent on the body and egg compartment. For example, tris(2-butoxyethyl) phosphate (TBOEP) accounted for 66% of the ΣOP concentration in albumen, but only for 13% in yolk. Tri-n-butyl phosphate (TNBP) accounted for 25% of the ΣOP concentration in yolk, but was not detected in albumen. Estimates showed that overall OP burdens in the body (3.5 μg) were greater than in the whole egg (1.2 μg), although depuration via in ovo transfer was substantial.

Perfluorooctane sulfonate (PFOS) is a globally distributed persistent organic pollutant that has been found to bioaccumulate and biomagnify in aquatic food webs. Although principally in its linear isomeric configuration, 21-35% of the PFOS manufactured via electrochemical fluorination is produced as a branched structural isomer. PFOS isomer patterns were investigated in multiple tissues of polar bears (Ursus maritimus) from East Greenland. The liver (n = 9), blood (n = 19), brain (n = 16), muscle (n = 5), and adipose (n = 5) were analyzed for linear PFOS (n-PFOS), as well as multiple mono- and di-trifluoromethyl-substituted branched isomers. n-PFOS accounted for 93.0 ± 0.5% of Σ-PFOS isomer concentrations in the liver, whereas the proportion was significantly lower (p

Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) is used as a flame retardant chemical and has been hypothesized to be the precursor of methoxylated polybrominated diphenoxybenzene (MeO-PB-DiPhOBz) contaminants reported in herring gulls from sites across the Laurentian Great Lakes. Here, by irradiating the parent TeDB-DiPhOBz (solution 1) with natural sunlight or UV, we prepared three solutions where solution 2 was dominated by the Br8-11-PB-DiPhOBzs, along with Br5-8-PB-DiPhOBzs (solution 3) and Br4-6-PB-DiPhOBzs (solution 4). The in vitro metabolism of TeDB-DiPhOBz and PB-DiPhOBzs was investigated using harvested wild herring gull (Larus argentatus) and adult male Wister-Han rat liver microsomal assays. After a 90 min incubation period of solution 1 in gull or rat microsomal assays, there was no significant (p > 0.05) depletion of TeDB-DiPhOBz. OH-PB-DiPhOBz metabolites were detectable after gull and rat microsomal assay incubation with solutions 3 or 4, and showed clear species-specific differences. Also detected were two polybrominated hydroxylated metabolites having polybenzofuran structures. Overall, this study suggested that TeDB-DiPhOBz is slowly metabolized in vitro, and also indicated that if wild herring gulls are exposed (e.g., via the diet) to photolytic products of TeDB-DiPhOBz, OH-PB-DiPhOBz and other metabolites could be formed. OH-PH-DiPhOBz are likely precursors to MeO-PB-DiPhOBz contaminants that we reported previously in eggs of wild Great Lakes herring gulls.

The in vitro biotransformation and kinetics of six organophosphate triester (OPE) flame retardants were investigated in herring gulls (Larus argentatus) from the Great Lakes using a hepatic microsomal metabolism assay. Administration of each individual OPE (tri-n-butyl phosphate (TNBP), tris(2-butoxyethyl) phosphate (TBOEP), triphenyl phosphate (TPHP), triethyl phosphate (TEP), tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) and tris(2-chloroisopropyl) phosphate (TCIPP)) to the in vitro assay (concentration range 0.01 to 10μM) resulted in rapid depletion with the exception of TEP. Following the Michaelis-Menten enzyme kinetics model, a preliminary 2-minute incubation period was used to estimate the Vmax (±SE) values (i.e., the maximal rate of reaction for a saturated enzyme system), which ranged from 5.0±0.4 (TPHP) to 29±18pmol/min/mg protein (TBOEP), as well as the KM (±SE) values (i.e., the OPE concentration corresponding to one half of the Vmax), which ranged from 9.8±1 (TPHP) to 189±135nM (TBOEP). Biotransformation assays over a 100-minute incubation period revealed that TNBP was metabolized most rapidly (with a depletion rate of 73±4pmol/min/mg protein), followed by TBOEP (53±8pmol/min/mg), TCIPP (27±1pmol/min/mg), TPHP (22±2pmol/min/mg) and TDCIPP (8±1pmol/min/mg). In vitro biotransformation of OP triesters was clearly structure-dependent where non-halogenated alkyl OP triesters were metabolized more rapidly than halogenated alkyl triesters. Halogenated OP triesters were transformed to their respective diesters more efficiently relative to non-halogenated OP triesters. To our knowledge, this is the first study to investigate OP triester metabolism and OP diester formation in an avian or wildlife model system, which is important to understand the fate and biological activity of OPEs in an exposed organism.

Several perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs) of varying chain length are bioaccumulative in biota. However, wildlife reports have focused on liver and with very little examination of other tissues, and thus there is a limited understanding of their distribution and potential effects in the mammalian body. In the present study, the comparative accumulation of C(6) to C(15) PFCAs, C(4), C(6), C(8) and C(10) PFSAs, and select precursors were examined in the liver, blood, muscle, adipose, and brain of 20 polar bears (Ursus maritimus) from Scoresby Sound, Central East Greenland. Overall, PFSA and PFCA concentrations were highest in liver followed by bloodbrainmuscle ≈ adipose. Liver and blood samples contained proportionally more of the shorter/medium chain length (C(6) to C(11)) PFCAs, whereas adipose and brain samples were dominated by longer chain (C(13) to C(15)) PFCAs. PFCAs with lower lipophilicities accumulated more in the liver, whereas the brain accumulated PFCAs with higher lipophilicities. The concentration ratios (±SE) between perfluorooctane sulfonate and its precursor perfluorooctane sulfonamide varied among tissues from 9 (±1):1 (muscle) to 36 (±7):1 (liver). PFCA and PFSA patterns in polar bears indicate that the pharmacokinetics of these compounds are to some extent tissue-specific, and are the result of several factors that may include differing protein interactions throughout the body.

The present study investigated the comparative accumulation of perfluoroalkyl acids (PFAAs) in eight brain regions of polar bears (Ursus maritimus, n = 19) collected in 2006 from Scoresby Sound, East Greenland. The PFAAs studied were perfluoroalkyl carboxylates (PFCAs, C(6) -C(15) chain lengths) and sulfonates (C(4) , C(6) , C(8) , and C(10) chain lengths) as well as selected precursors including perfluorooctane sulfonamide. On a wet-weight basis, blood-brain barrier transport of PFAAs occurred for all brain regions, although inner regions of the brain closer to incoming blood flow (pons/medulla, thalamus, and hypothalamus) contained consistently higher PFAA concentrations compared to outer brain regions (cerebellum, striatum, and frontal, occipital, and temporal cortices). For pons/medulla, thalamus, and hypothalamus, the most concentrated PFAAs were perfluorooctane sulfonate (PFOS), ranging from 47 to 58 ng/g wet weight, and perfluorotridecanoic acid, ranging from 43 to 49 ng/g wet weight. However, PFOS and the longer-chain PFCAs (C(10) -C(15) ) were significantly (p 0.002) positively correlated with lipid content for all brain regions. Lipid-normalized PFOS and PFCA (C(10) -C(15) ) concentrations were not significantly (p 0.05) different among brain regions. The burden of the sum of PFCAs, perfluoroalkyl sulfonates, and perfluorooctane sulfonamide in the brain (average mass, 392 g) was estimated to be 46 µg. The present study demonstrates that both PFCAs and perfluoroalkyl sulfonates cross the blood-brain barrier in polar bears and that wet-weight concentrations are brain region-specific.