Abstract  Eleven perfluorinated alkyl acids (PFAAs) were analyzed in plasma from a total of 600 American Red Cross adult blood donors from six locations in 2010. The samples were extracted by protein precipitation and quantified by using liquid chromatography tandem mass spectrometry (HPLC/MS/MS). The anions of the three perfluorosulfonic acids measured were perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS). The anions of the eight perfluorocarboxylic acids were perfluoropentanoate (PFPeA), perfluorohexanoate (PFHxA), perfluoroheptanoate (PFHpA), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA). Findings were compared to results from different donor samples analyzed at the same locations collected in 2000-2001 (N = 645 serum samples) and 2006 (N = 600 plasma samples). Most measurements in 2010 were less than the lower limit of quantitation for PFBS, PFPeA, PFHxA, and PFDoA. For the remaining analytes, the geometric mean concentrations (ng/mL) in 2000-2001, 2006, and 2010 were, respectively, PFHxS: (2.25, 1.52, 1.34); PFOS (34.9, 14.5, 8.3); PFHpA (0.13, 0.09, 0.05); PFOA (4.70, 3.44, 2.44); PFNA (0.57, 0.97, 0.83); PFDA (0.16, 0.34, 0.27), and PFUnA (0.10, 0.18, 0.14). The percentage decline (parentheses) in geometric mean concentrations from 2000-2001 to 2010 were PFHxS (40%), PFOS (76%), and PFOA (48%). The decline in PFOS suggested a population halving time of 4.3 years. This estimate is comparable to the geometric mean serum elimination half-life of 4.8 years reported in individuals. This similarity supports the conclusion that the dominant PFOS-related exposures to humans in the United States were greatly mitigated during the phase-out period.

Abstract  For the analysis of perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) in shells, an extraction method of mixed inorganic acid digestion coupled with solid phase extraction (SPE) was established. The target compounds were determined by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The shell powder was at first digested with the mixture of nitric acid and hydrochloric acid, then the digestion solution was adjusted to pH 6 with sodium hydroxide, and cleaned up with Oasis WAX SPE cartridge. The perfluoro sulfonated chemicals were quantified with HPLC-MS/MS using electrospray ionization in negative ion mode with internal standard method. The limits of detection (LODs) were of 0.28 ng/g for PFBS, 0.42 ng/g for PFHxS and 0.43 ng/g for PFOS, and matrix recoveries of the perfluoro sulfonated chemicals were 94.88%-96.24%. The analytical results for the shells of two bivalves from Bohai Bay showed this pretreatment method is suitable for the determination of perfluoro sulfonated acids (PFSAs) in shells. Concentrations of PFSAs in the shells ranged from < LOD-0.70 ng/g, which were an order of magnitude lower than those in the soft tissues of these bivalves.

Abstract  The influence of the addition of powder on the viscoelasticity of carboxyvinylpolymer (CVP) hydrogel was studied by the oscillation method. The powder-filled hydrogels (PFHs) were prepared using Hiviswako 103 and 105 (CVP of rich side chains and poor side chains, respectively), and six powders [zinc oxide (ZnO), titanium dioxide (TiO2), magnesium stearate (StMg), talc, synthetic aluminum silicate (SiAl), and hydrated silicone dioxide (Cp)].

The profiles of storage modulus (G') and loss modulus (G") of each PFH differed depending on powder and CVP. log G' and log G" changed little with TiO2, monotonously increased with talc, StMg and Cp, and showed fairly complex behaviors differing with polymer species with ZnO and SiAl. Plotting according to the Kerner equation suggested that powder bridge structures were formed in the PFHs.

The possible structures formed in the PFHs were presumed as follows on the basis of their viscoelasticity change and microscopic observation. With TiO2: the original hydrogel network was not ruptured and powders were dispersed uniformly in the gel network. With talc, StMg and Cp: the original hydrogel networks and the powder bridge structures coexisted. With ZnO and SiAl: the original hydrogel networks were ruptured and powder bridge structures

Abstract  BACKGROUND: Immune suppression may be a critical effect associated with exposure to perfluorinated compounds (PFCs), as indicated by recent data on vaccine antibody responses in children. Therefore, this information may be crucial when deciding on exposure limits. METHODS: Results obtained from follow-up of a Faroese birth cohort were used. Serum-PFC concentrations were measured at age 5 years, and serum antibody concentrations against tetanus and diphtheria toxoids were obtained at ages 7 years. Benchmark dose results were calculated in terms of serum concentrations for 431 children with complete data using linear and logarithmic curves, and sensitivity analyses were included to explore the impact of the low-dose curve shape. RESULTS: Under different linear assumptions regarding dose-dependence of the effects, benchmark dose levels were about 1.3 ng/mL serum for perfluorooctane sulfonic acid and 0.3 ng/mL serum for perfluorooctanoic acid at a benchmark dose response of 5%. These results are below average serum concentrations reported in recent population studies. Even lower results were obtained using logarithmic dose--response curves. Assumption of no effect below the lowest observed dose resulted in higher benchmark dose results, as did a benchmark response of 10%. CONCLUSIONS: The benchmark dose results obtained are in accordance with recent data on toxicity in experimental models. When the results are converted to approximate exposure limits for drinking water, current limits appear to be several hundred fold too high. Current drinking water limits therefore need to be reconsidered.

Abstract  Exposure of mice to perfluorooctanoate (PFOA) evokes pronounced hepatomegaly along with significant alterations in both the histological structure and immune status of the liver. The present study was designed to evaluate the effects of this perfluorochemical on immune-mediated liver damage. In this connection, the influence of both sub-acute (10 days), moderate-dose (0.002% w/w=3±0.7mg/kg body weight/day) and short-term (28 days), low-dose (0.00005% w/w=70±2μg/kg body weight/day) dietary pretreatment with PFOA on the development of concanavalin A (Con A)-induced liver damage in mice was examined. With sub-acute, moderate, but not short-term, low-dose exposure, PFOA aggravated the acute liver damage caused by Con A, i.e., elevated serum levels of transaminases and led to more pronounced damage of hepatic tissue. This aggravation was associated with significantly enhanced hepatic level of interleukin-6 (IL-6), but unaltered hepatic levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-4 (IL-4). Moreover, hepatic DNA fragmentation was not changed by sub-acute exposure to the moderate-dose. Our findings imply that exposure to PFOA may sensitize hepatic parenchymal cells to other toxicants that activate the hepatic immune system and thereby aggravate liver injury during acute inflammation.

Abstract    Perfluorinated organic compounds (PFOCs) are emerging persistent organic pollutants (POPs) widely distributed in the environment, wildlife and human. We studied the toxicology of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on immunotoxicity and hepatotoxicity in primarily cultured hepatocytes of freshwater tilapia (Oreochromis niloticus). Cultured hepatocytes were exposed to PFOS or PFOA (0, 10, 20 and 30 mg/L) for 24, 48, 72, 96, 120 and 144 hours, respectively. Oral doses of these compounds that induce significantly detectable immunotoxicity and hepatotoxicity were employed in the study. In response to PFOS, the leukocytes, B cells, granulocytes, and macrophages among the isolation of intrahepatic immune cells (IHIC) from PFOS-treated tilapia produced significant levels of immune cells compared with that of the control group. The numbers of leukocytes, B cells, granulocytes, and macrophages for PFOS-treated tilapia increased with the incremental exposure concentration. Moreover, similar to the findings in PFOA toxicity effects, the erythropoietin levels in tilapia increased with the increase of the PFOS and PFOA concentrations. The lowest doses (10 mg/L) of PFOS exposure led to a marked inhibition in the hepatocyte viability in tilapia. Similarly, tilapia exposed to PFOA demonstrated a similar pattern, and a dose-dependent decrease in the hepatocyte viability was observed in the following treatment of PFOA. In the 72 h exposures, ethoxy-resorufin-O-deethylase (EROD) activity was significantly induced with the increase concentrations in tilapia liver (p<0.05). Tilapia showed a strong EROD induction in livers, and significantly difference in EROD activity was observed between control, PFOS and PFOA-exposed tilapias. The liver glycogen content showed that PFOS and PFOA exposure caused significant changes in the liver glycogen content, which depended on the duration of exposure. And it appeared that the decrease in blood glucose level during the acclimation was followed by significant increase in liver glycogen content in tilapia.[PUBLICATION ABSTRACT]

Abstract  Perfluorinated acids are anthropogenic pollutants with primarily two industrial synthetic routes: electrochemical fluorination (ECF) and telomerization. A mixture of structural isomers is produced by ECF, while telomerization conserves the geometry of its starting materials, which are typically linear. To contribute to a discussion on sources of perfluorinated acid pollution, isomer profiles of perfluorinated carboxylates (PFCAs) were determined in a diverse set of environmental and biotic samples from remote to urban locations. Analysis was conducted on the derivatized extracts using gas chromatography/mass spectrometry. The perfluorooctanoate (PFOA) isomer profile in most samples contained linear and branched isomers congruent with an ECF input, but linear PFOA (n-PFOA) predominated (>90%) greater than in the ECF technical product (78%). The perfluorononanoate (PFNA) isomer pattern varied from only n-PFNA, n- and iso-PFNA (isopropyl isomer), or n-PFNA and multiple branched isomers. At midlatitudes, PFNA isomer profiles containing multiple branched isomers are attributed to ECF sources such as impurities in ECF PFOA. In surface water from Lake Ontario (Canada) and an Arctic lake, only n- and iso-PFNA were observed. Human and dolphin blood contained multiple branched PFNA, consistent with an ECF signature albeit n-isomer enriched. Both n- and isopropyl isomers of longer-chain PFCAs were observed with a distinct pattern for dolphin and Arctic samples compared to those from the Lake Ontario ecosystem. These results support the hypothesis that long-range atmospheric transport of linear volatile precursors, subsequent degradation, and deposition contribute to the presence of n-PFCAs in the Arctic freshwater environment. The presence of longer-chain isopropyl isomers may be preliminary evidence of isopropyl fluorinated organic precursors.

Abstract  In this study we report the human plasma concentrations of some common endocrine disrupting chemicals (EDCs) in the Hong Kong population. We have analyzed 153 plasma samples for the contaminants by methods involving labeled standards spiked into the samples. Quantification was performed using high performance liquid chromatography tandem mass spectrometry for bisphenol-A (BPA) and perfluorinated compounds (PFCs), and gas chromatography mass spectrometry methods for phthalates. We found BPA, several types of PFCs and phthalates in over 90% of the plasma samples. Perfluorooctane sulfonate (PFOS) was the dominant PFC, followed by perfluroroctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS). Eight out of ten phthalates were detected, with bis(2-ethylhexyl) phthalate (DEHP) as the most abundant, followed by bis(2-methoxyethyl) phthalate (DMEP) and dioctyl phthalate (DnOP). The levels of PFOS, PFOA, PFHxS and perfluorohexanoic acid (PFHxA) were significantly higher in the male plasma samples (p<0.05), while the mean plasma levels of DEHP and n-butyl benzyl phthalate (BBP) were significantly higher in the young age group (p<0.02). The presence of the selected EDCs in human blood plasma indicates common exposure routes among different population cohorts. Although the plasma levels of the EDCs were comparable to other countries, regular monitoring of human blood EDC contamination levels is necessary to provide a time-trend database for the estimation of exposure risk and to formulate appropriate public health policy.

Abstract  Organic fluorochemicals are used in multiple commercial applications including surfactants, lubricants, paints, polishes, food packaging, and fire-retarding foams. Recent scientific findings suggest that several perfluorochemicals (PFCs), a group of organic fluorochemicals, are ubiquitous contaminants in humans and animals worldwide. Furthermore, concern has increased about the toxicity of these compounds. Therefore, monitoring human exposure to PFCs is important. We have developed a high-throughput method for measuring trace levels of 13 PFCs (2 per-fluorosulfonates, 8 perfluorocarboxylates, and 3 perfluorosulfonamides) in serum and milk using an automated solid-phase extraction (SPE) cleanup followed by high-performance liquid chromatography-tandem mass spectrometry. The method is sensitive, with limits of detection between 0.1 and 1 ng in 1 mL of serum or milk, is not labor intensive, involves minimal manual sample preparation, and uses a commercially available automated SPE system. Our method is suitable for large epidemiologic studies to assess exposure to PFCs. We measured the serum levels of these 13 PFCs in 20 adults nonoccupationally exposed to these compounds. Nine of the PFCs were detected in at least 75% of the subjects. Perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS), 2-(N-methylperfluorooctanesulfonamido)acetate (Me-PFOSA-AcOH), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA) were found in all of the samples. The concentration order and measured levels of PFOS, PFOA, Me-PFOSA-AcOH, and PFHxS compared well with human serum levels previously reported. Although no human data are available for the perfluorocarboxylates (except PFOA), the high frequency of detection of PFNA and other carboxylates in our study suggests that human exposure to long-alkyl-chain perfluorocarboxylates may be widespread. We also found PFOS in the serum and milk of rats administered PFOS by gavage, but not in the milk of rats not dosed with PFOS. Furthermore, we did not detect most PFCs in two human milk samples. These findings suggest that PFCs may not be as prevalent in human milk as they are in serum. Additional studies are needed to determine whether environmental exposure to PFCs can result in PFCs partitioning into milk. Large epidemiological studies to determine the levels of PFCs among the U.S. general population are warranted.

Abstract  Perfluoroalkyl substances (PFASs) are protein-binding blood-accumulating contaminants that may have detrimental toxicological effects on the early phases of mammalian development. To enable an evaluation of the potential health risks of PFAS exposure for polar bears (Ursus maritimus), an exposure assessment was made by examining plasma levels of PFASs in polar bear mothers in relation to their suckling cubs-of-the-year (~4 months old). Samples were collected at Svalbard in 1998 and 2008, and we investigated the between-year differences in levels of PFASs. Seven perfluorinated carboxylic acids (∑₇PFCAs: PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, and PFTrDA) and two perfluorinated sulfonic acids (∑₂PFSAs: PFHxS and PFOS) were detected in the majority of the mothers and cubs from both years. In mothers and cubs, most PFCAs were detected in higher concentrations in 2008 than in 1998. On the contrary, levels of PFOS were lower in 2008 than in 1998, while levels of PFHxS did not differ between the two sampling years. PFOS was the dominating compound in mothers and cubs both in 1998 and in 2008. Concentration of PFHpA did not differ between mothers and cubs, while concentrations of PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTrDA, PFHxS, and PFOS were higher in mothers than in their cubs. Except from PFHpA, all compounds correlated significantly between mothers and their cubs. The mean cub to mother ratios ranged from 0.15 for PFNA to 1.69 for PFHpA. On average (mean±standard error of mean), the levels of ∑₇PFCAs and ∑₂PFSAs in cubs were 0.24±0.01 and 0.22±0.01 times the levels in their mothers, respectively. Although maternal transfer appears to be a substantial source of exposure for the cubs, the low cub to mother ratios indicate that maternal transfer of PFASs in polar bears is relatively low in comparison with hydrophobic contaminants (e.g. PCBs). Because the level of several PFASs in mothers and cubs from both sampling years exceeded the levels associated with health effects in humans, our findings raise concern on the potential health effects of PFASs in polar bears from Svalbard. Effort should be made to examine the potential health effects of PFASs in polar bears.

Abstract  In 2006, California passed legislation establishing the first State Biomonitoring Program in the USA. The main goals are to: 1) Determine levels of environmental chemical contaminants in a representative sample of Californians; 2) Establish trends in the levels of these chemicals over time; 3) Assess the effectiveness of public health efforts and regulatory programs to decrease exposures to specific chemicals.

As part of the Biomonitoring Program, our laboratory will be conducting analyses for Persistent Organic Pollutants (POPs) such as organochlorine pesticides (OCPs), PCBs, polybrominated diphenyl ethers (PBDEs), perfluorinated chemicals (PFCs), triclosan, phenols, OH-PCBs and OH-PBDEs. Prior to this program, we had conducted a number of epidemiologic studies using specimens collected from the 1960s to the present and analysing them for POPs. Serum, milk and adipose samples were extracted and the neutral fractions were cleaned up using deactivated Florisil column chromatography, and analyzed for PCBs, OCPs and PBDEs by dual column GC-ECD and/or High Resolution Mass Spectrometry. Online Solid Phase Extraction - HPLC- Turbo ion Spray Tandem Mass Spectrometry was used to analyze PFCs. Following standard conventions, results are expressed on a lipid basis (PCBs, PBDEs, OCPs), or on a volume basis (PFCs, Triclosan, Phenols, OH-PCBs, OH-PBDEs). A Quality Management system tracks all laboratory work.

We had first reported the absence of PBDEs in serum samples from 1960s California populations as opposed to their presence in samples collected in the 1990s. We confirmed this observation with the analysis of over 1500 samples from the 1960s. In contemporary serum, the abundance of PBDE congeners was in the order of BDE-47>153>99>100, while BDE-209 was measurable in only a few of the samples. We could trace the increase of PFOA from the1960s to the 1980s, followed by a slight decrease in 2009. On the other hand, PFOS and PFHxS were highest in the 1960s, with similar decreasing trends from the1980s to 2009.

In addition to addressing the research hypotheses of each epidemiologic study, data compiled across studies can show trends such as the emergence of PBDEs, and the decline in PCBs, phenols, OCPs and some PFCs over time. In addition, determinants of exposures (age, country of birth, ethnicity and reproductive history) can be identified, allowing for optimal sampling designs to account for the population diversity in California and can also be used in questionnaires to assess exposures. These data help establish a baseline before the new Biomonitoring Program launches its state-wide surveys.

Abstract  Perfluoroalkyl acids (PFAAs) are globally found in various media, including food and especially fishery products. In the present study, the dietary exposure to 15 perfluoroalkyl acids was assessed for 3 French adult populations, namely high seafood consumers, high freshwater fish consumers, and pregnant women. Purified food extracts were analysed by LC-MS/MS and PFBA, PFPA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnA, PFTrDA, PFTeDA, PFBS, PFHxS, PFHpS, PFOS and PFDS were monitored and quantified according to the isotope dilution principle. Under lower bound (LB) hypothesis (i.e. contamination values<LOD considered as 0), high freshwater fish consumers appear as the most exposed to PFOS (7.5ng.kg(-1) bw.d(-1)), PFUnA (1.3ng.kg(-1) bw.d(-1)), PFDA (0.4ng.kg(-1) bw.d(-1)) and PFHpS (0.03ng.kg(-1) bw.d(-1)) while high seafood consumers appear as the most exposed to PFOA (1.2ng.kg(-1) bw.d(-1)), PFNA (0.2ng.kg(-1) bw.d(-1)) and PFHxS (0.06ng.kg(-1) bw.d(-1)). For all considered populations, the major exposure contributors are fish, seafood and water under LB hypothesis, while dairy products, bread and crispbread are the main contributors under upper bound (UB) hypothesis. Besides this food exposure assessment, further studies are needed to assess the more global PFAA exposure, taking into account indoor and outdoor air, dust and cutaneous contact, which could be other important contributors for this particular class of chemicals.

Abstract  The distribution in water and sediment, the sources/sinks and the risk of perfluorinated compounds (PFCs) in Lake Taihu, China were investigated. The total PFCs concentration was 164 to 299ngL(-1) in water and 5.8 to 35ngg(-1) (dw) in sediment. The highest concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in water were 29.2ngL(-1) and 136ngL(-1). PFOS was largely associated with sediment, whereas short chain PFCs predominated in water. The partition coefficient (Kd) was positively correlated with the organic carbon fraction (ƒoc) for PFOS but not for the other PFCs. The organic carbon normalized partition coefficient (Koc) increased by 0.51 log units for each additional CF2 moiety from perfluoro-butanesulfonate (PFBS) to PFOS. For the same chain length but different functional groups, the log Koc of PFOS was 1.35 units higher than PFOA. PFOS exhibited the highest affinity for sediment through the partition mechanism, and ƒoc affected the sediment as a sink of PFOS. Although there was no immediate health impact by the intake of the water alone, the consumption of aquatic products may cause potential health risks for animals/humans on the time scale of months to years. The relationship between the concentration, water-sediment distribution, bioaccumulation and toxicity should be considered in determining the water standards of PFCs.

Abstract  The perfluoroalkyl compounds (PFCs), perfluoroalkyl sulfonates (PFXS) and perfluoroalkyl carboxylates (PFXA) are environmentally persistent and recalcitrant towards most conventional water treatment technologies. Here, we complete an in depth examination of the UV-254 nm production of aquated electrons during iodide photolysis for the reductive defluorination of six aquated perfluoroalkyl compounds (PFCs) of various headgroup and perfluorocarbon tail length. Cyclic voltammograms (CV) show that a potential of +2.0 V (vs. NHE) is required to induce PFC oxidation and -1.0 V is required to induce PFC reduction indicating that PFC reduction is the thermodynamically preferred process. However, PFCs are observed to degrade faster during UV(254 nm)/persulfate (S(2)O(8)(2-)) photolysis yielding sulfate radicals (E° = +2.4 V) as compared to UV(254 nm)/iodide (I(-)) photolysis yielding aquated electrons (E° = -2.9 V). Aquated electron scavenging by photoproduced triiodide (I(3)(-)), which achieved a steady-state concentration proportional to [PFOS](0), reduces the efficacy of the UV/iodide system towards PFC degradation. PFC photoreduction kinetics are observed to be dependent on PFC headgroup, perfluorocarbon chain length, initial PFC concentration, and iodide concentration. From 2 to 12, pH had no observable effect on PFC photoreduction kinetics, suggesting that the aquated electron was the predominant reductant with negligible contribution from the H-atom. A large number of gaseous fluorocarbon intermediates were semi-quantitatively identified and determined to account for ∼25% of the initial PFOS carbon and fluorine. Reaction mechanisms that are consistent with kinetic observations are discussed.

Abstract  Perfluorinated chemicals (PFCs) are distributed throughout the environment. In the case of perfluorinated alkyl carboxylates and sulfonates, they can be classified as persistent organic pollutants since they are resistant to environmentally relevant reduction, oxidation, and hydrolytic processes. With this in mind, we report on the reductive defluorination of perfluorobutanoate, PFBA (C(3)F(7)CO(2)(-)), perfluorohexanoate, PFHA (C(5)F(11)CO(2)(-)), perfluorooctanoate, PFOA (C(7)F(15)CO(2)(-)), perfluorobutane sulfonate, PFBS (C(4)F(9)SO(3)(-)), perfluorohexane sulfonate, PFHS (C(6)F(13)SO(3)(-)), and perfluorooctane sulfonate, PFOS (C(8)F(17)SO(3)(-)) by aquated electrons, e(aq)(-), that are generated from the UV photolysis (lambda = 254 nm) of iodide. The ionic headgroup (-SO(3)(-) vs -CO(2)(-)) has a significant effect on the reduction kinetics and extent of defluorination (F index = -[F(-)](produced)/[PFC](degraded)). Perfluoroalkylsulfonate reduction kinetics and the F index increase linearly with increasing chain length. In contrast, perfluoroalkylcarboxylate chain length appears to have a negligible effect on the observed kinetics and the F index. H/F ratios in the gaseous fluoro-organic products are consistent with measured F indexes. Incomplete defluorination of the gaseous products suggests a reductive cleavage of the ionic headgroup occurs before complete defluorination. Detailed mechanisms involving initiation by aquated electrons are proposed.

Abstract  Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics, and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits, and nonhuman primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. Although not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable.

Abstract  Preferential distribution of long-chain perfluoroalkyl acids (PFAAs) in the liver, kidney, and blood of organisms highlights the importance of PFAA-protein interactions in PFAA tissue distribution patterns. A serum protein association constant may be a useful parameter to characterize the bioaccumulative potential and in vivo bioavailability of PFAAs. In this work, association constants (K(a)) and binding stoichiometries for PFAA-albumin complexes are quantified over a wide range of PFAA:albumin mole ratios. Primary association constants for perfluorooctanoate (PFOA) or perfluorononanoate (PFNA) with the model protein bovine serum albumin (BSA) determined via equilibrium dialysis are on the order of 10(6) M(-1) with one to three primary binding sites. PFNA was greater than 99.9% bound to BSA or human serum albumin (HSA) at a physiological PFAA:albumin mole ratio (<10(-3)), corresponding to a high protein-water distribution coefficient (log K(PW) > 4). Nanoelectrospray ionization mass spectrometry (nanoESI-MS) data reveal PFAA-BSA complexes with up to eight occupied binding sites at a 4:1 PFAA:albumin mole ratio. Association constants estimated by nanoESI-MS are on the order of 10(5) M(-1) for PFOA and PFNA and 10(4) M(-1) for perfluorodecanoate and perfluorooctanesulfonate. The results reported here suggest binding through specific high affinity interactions at low PFAA:albumin mole ratios.

Abstract  Interactions of perfluoroalkyl acids (PFAAs) with tissue and serum proteins likely contribute to their tissue distribution and bioaccumulation patterns. Protein-water distribution coefficients (K(PW) ) based on ligand associations with bovine serum albumin (BSA) as a model protein were recently proposed as biologically relevant parameters to describe the environmental behavior of PFAAs, yet empirical data on such protein binding behavior are limited. In the present study, associations of perfluoroalkyl carboxylates (PFCAs) with two to 12 carbons (C₂-C₁₂) and perfluoroalkyl sulfonates with four to eight carbons (C₄, C₆, and C₈) with BSA are evaluated at low PFAA:albumin mole ratios and various solution conditions using equilibrium dialysis, nanoelectrospray ionization mass spectrometry, and fluorescence spectroscopy. Log K(PW) values for C₄ to C₁₂ PFAAs range from 3.3 to 4.3. Affinity for BSA increases with PFAA hydrophobicity but decreases from the C₈ to C₁₂ PFCAs, likely due to steric hindrances associated with longer and more rigid perfluoroalkyl chains. The C₄-sulfonate exhibits increased affinity relative to the equivalent chain-length PFCA. Fluorescence titrations support evidence that an observed dependence of PFAA-BSA binding on pH is attributable to conformational changes in the protein. Association constants determined for perfluorobutanesulfonate and perfluoropentanoate with BSA are on the order of those for long-chain PFAAs (K(a) ∼10⁶/M), suggesting that physiological implications of strong binding to albumin may be important for short-chain PFAAs.

Abstract  Spatial trends of concentrations of perfluorinated chemicals (PFCs) were investigated in harbour seal liver tissue from seven locations in Denmark, ranging from the Wadden Sea in the southern North Sea to the Western Baltic. All samples were collected during the phocine distemper epizootic in 2002 which provided access to a large number of comparable samples over a short time period. PFOS was dominating (mean: 92% of ∑PFC) among the PFCs in the samples, followed by considerably lower concentrations of PFHxS (1.8%), PFDA (1.7%), PFNA (1.6%) PFUnA (1.5%), PFOA (0.9%) and PFOSA (0.5%). The concentrations of all the investigated compounds showed significant differences among the seven locations. PFOS showed the highest concentrations in the Wadden Sea, where high burdens have also been recorded in German seals. Most compounds showed a trend towards higher concentrations at one or both extremes of the geographic range. Two different patterns of relative PFC concentrations were detected; one in the inner Danish waters where PFOSA and PFUnA were more prevalent and another in the Wadden Sea and Limfjord where PFOA, PFHxS and PFNA were found in greater proportions. These patterns probably represent Baltic and North Sea contamination sources.

Abstract  Perfluorooctanesulfonate (PFOS) at 1.6-39 ng/g ww and 4.8-200 pg/mL, respectively, perfluorooctanoate (PFOA) at 0.06-0.28 ng/g ww and<0.05-1.8 pg/mL, and perfluorodecanoate (PFDA) at 0.13-0.57 ng/g ww and 0.05-1.8 pg/mL, were detected in all specimens of European Beaver's (Castor fiber) liver as well as in whole blood of Cod (Gadus morhua), Velvet Scoter (Melanitta fusca), Eider Duck (Sommateria mollisima), Long-tailed Duck (Clangula hyemalis), Razorbill (Alca torda), Red-throated Diver (Gavia stellata) sampled in Poland. At smaller concentrations and at less frequency was perfluorononanoate (PFNA) at 0.05-1.4 ng/g ww and<0.2-2 pg/mL, perfluorohexanoate (PFHxA) at 0.03-0.23 ng/g ww and<0.05-0.69 pg/mL, while perfluorohexanesulfonate (PFHxS) at 0.05-4.3 pg/mL and perfluorooctanesulfonamidoacetate (PFOSA) at 0.1-13 pg/mL were also found in Cod as well as in molluscivorous diving-ducks and fish-eating birds but not in Beaver, while perfluoroheptanoate (PFHpA) at<0.05-0.74 pg/mL was found only in Cod.

Abstract  Perfluorinated compounds (PFCs) are environmentally widespread, persistent, and bioaccumulative chemicals with multiple toxicities reported in experimental models and wildlife, including immunomodulation. The two most commonly detected compounds, which also generally occur in the highest concentrations in environmentally exposed organisms, are perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). PFOA and PFOS have been reported to alter inflammatory responses, production of cytokines, and adaptive and innate immune responses in rodent models, avian models, reptilian models, and mammalian and nonmammalian wildlife. Mounting evidence suggests that immune effects in laboratory animal models occur at serum concentrations below, within the reported range, or just above those reported for highly exposed humans and wildlife. Thus, the risk of immune effects for humans and wildlife exposed to PFCs cannot be discounted, especially when bioaccumulation and exposure to multiple PFCs are considered. This review contains brief descriptions of current and recently published work exploring immunomodulation by PFOA, PFOS, and other PFCs in rodent models, alternative laboratory models, and wildlife.

Abstract  In the first part of a series of studies to account for perfluorooctane sulfonate (PFOS)-induced sheep red blood cell (SRBC)-specific immunoglobulin M (IgM) antibody suppression in mice, a survey of clinical and immunotoxicological endpoints was examined. Adult female B₆C₃F₁ mice were exposed orally for 28 days to a total administered dose (TAD) of 0, 0.1, 0.5, 1, or 5 mg PFOS/kg. Uterus wet weight was significantly decreased compared with control at the 5 mg/kg dose. No indications of wasting syndrome, malnutrition, alteration of thyroid homeostasis, or signs of overt toxicity were observed. Numbers of splenic CD19+/CD21⁻, CD19+/CD21+, B220+/CD40+, CD4+/CD154⁻, CD4+/CD154+, and MHC-II+ cells were not altered. Additionally, ex vivo interleukin-4 (IL-4), IL-5, and IL-6 production by in vitro anti-CD3- or phorbol myristate acetate-stimulated CD4+ T-cells was not affected. Ex vivo IL-6 production by B-cells was significantly increased by in vitro stimulation with either anti-CD40 or lipopolysaccharide. Increased IL-6 production by B-cells was the most sensitive endpoint assessed resulting in alterations at the lowest dose tested (0.1 mg/kg TAD) following anti-CD40 stimulation. Further studies are required to characterize effects on inflammatory markers such as IL-6 at environmentally relevant concentrations of PFOS and to determine the key events associated with PFOS-induced IgM suppression to address potential human health risks.

Abstract  Perfluorooctanoic acid (PFOA), a member of the perfluoroalkyl acids that have wide commercial applications, has recently been detected in humans and wildlife. The current study characterizes the developmental toxicity of PFOA in the mouse. Timed-pregnant CD-1 mice were given 1, 3, 5, 10, 20, or 40 mg/kg PFOA by oral gavage daily from gestational day (GD) 1 to 17; controls received an equivalent volume (10 ml/kg) of water. PFOA treatment produced dose-dependent full-litter resorptions; all dams in the 40-mg/kg group resorbed their litters. Weight gain in dams that carried pregnancy to term was significantly lower in the 20-mg/kg group. At GD 18, some dams were sacrificed for maternal and fetal examinations (group A), and the rest were treated once more with PFOA and allowed to give birth (group B). Postnatal survival, growth, and development of the offspring were monitored. PFOA induced enlarged liver in group A dams at all dosages, but did not alter the number of implantations. The percent of live fetuses was lower only in the 20-mg/kg group (74 vs. 94% in controls), and fetal weight was also significantly lower in this group. However, no significant increase in malformations was noted in any treatment group. The incidence of live birth in group B mice was significantly lowered by PFOA: ca. 70% for the 10- and 20-mg/kg groups compared to 96% for controls. Postnatal survival was severely compromised at 10 or 20 mg/kg, and moderately so at 5 mg/kg. Dose-dependent growth deficits were detected in all PFOA-treated litters except the 1-mg/kg group. Significant delays in eye-opening (up to 2-3 days) were noted at 5 mg/kg and higher dosages. Accelerated sexual maturation was observed in male offspring, but not in females. These data indicate maternal and developmental toxicity of PFOA in the mouse, leading to early pregnancy loss, compromised postnatal survival, delays in general growth and development, and sex-specific alterations in pubertal maturation.

Abstract  This text provides a concise and clearly presented discussion of all the elements in a meta-analysis. It is illustrated with worked examples throughout, with visual explanations, using screenshots from Excel spreadsheets and computer programs such as Comprehensive Meta-Analysis (CMA) or Strata.

Abstract  The concentrations of four perfluorinated sulfonate acids (PFSAs) and 10 perfluorinated carboxylate acids (PFCAs) were measured in water and sediment samples from Liao River and Taihu Lake, China. In the water samples from Taihu Lake, PFOA and PFOS were the most detected perfluorinated compounds (PFCs); in Liao River, PFHxS was the predominant PFC followed by PFOA, while PFOS was only detected in two of the samples. This suggests that different PFC products are used in the two regions. PFOS and PFOA in both watersheds are at similar level as in the rivers of Japan, but significantly lower than in Great Lakes. The contributions of PFOS and long chain PFCAs in sediments were much higher than in water samples of both watersheds, indicating preferential partition of these PFCs in sediment. The concentrations of PFOS and PFOA were three orders of magnitude of lower than that of polycyclic aromatic hydrocarbons in the same sediments. The average sediment-water partition coefficients (log K(oc)) of PFHxS, PFOS and PFOA were determined to be 2.16, 2.88 and 2.28 respectively.