Abstract  Perfluorinated compounds (PFCs) are man-made fluoro-surfactants that are identified as global pollutants and can pose health risks to humans and wildlife. Two aspects of risk assessment were conducted in this study, including exposure and response. Exposure was estimated by using the concentrations of PFCs in fish and applying standard exposure factors. Among different PFCs, PFOS, PFOA, PFNA, PFDA, PFUdA and PFTrDA were detected. Total concentrations of PFC in fish ranged from 0.27-8.4 ng g(-1) to 0.37-8.7 ng g(-1) respectively in Hong Kong and Xiamen. The calculated hazard ratio (HR) of PFOS for all fish was less than 1.0. However, the HR for mandarin fish in Hong Kong and bighead carp, grass carp and tilapia in Xiamen, had HR values of approximately 0.5, indicating that frequent consumption of these 4 more contaminated fish species might pose an unacceptable risk to human health. Our data support the notion that the released/disposed chemical pollutants into water systems make fish a source of environmental toxicants to humans. The risks and potential effects of PFCs to health of coastal population in the Pearl River Delta are of concern.

Abstract  A total of 21 perfluorinated compounds (PFCs) were quantified in water and biota samples collected from Shenyang in North-east China and the Yangtze River Delta area in East China. The human health risk owing to intake of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) via fish and domestic poultry dietary was evaluated. The total PFC concentration (Sigma PFC) in water samples from the rivers in Shenyang averaged 5.32 ng L(-1), with PFOS and PFOA as the predominant compounds. The urban sewage could be the source of PFOS and perfluorohexane sulfonate (PFHxS) in the surface waters. The total PFCs in water samples from the Yangtze River Delta area ranged from 42.4 to 170 ng L(-1). The highest concentrations of most PFCs were observed in waters from the Shanghai section of the Yangtze River. In the biota samples, PFOS and PFUnDA (perfluoroundecanoic acid) were the most abundant. The acceptable daily intake (ADI) and hazard ratio (HR) values for PFOS and PFOA intake through the diet of fish and poultry in the studied areas were calculated, and showed that the HR values for PFOS and PFOA are all less than 1.0 for both the areas.

Abstract  Perfluorinated compounds (PFCs) are known to biomagnify in temperate and Arctic food webs, but little is known about their behavior in subtropical systems. The environmental distribution and biomagnification of PFCs, extractable organic fluorine (EOF), and total fluorine were investigated in a subtropical food web. Surface water, sediment, phytoplankton, zooplankton, gastropods, worms, shrimps, fishes, and waterbirds collected in the Mai Po Marshes Nature Reserve in Hong Kong were analyzed. Trophic magnification was observed for perfluorooctanesulfonate (PFOS), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnDA), and perfluorododecanoate (PFDoDA) in this food web. Risk assessment results for PFOS, PFDA, and perfluorooctanoate (PFOA) suggest that current PFC concentrations in waterbird livers are unlikely to pose adverse biological effects to waterbirds. All hazard ratio (HR) values reported for PFOS and PFOA are less than one, which suggests that the detected levels will not cause any immediate health effects to the Hong Kong population through the consumption of shrimps and fishes. However, only 10-12% of the EOF in the shrimp samples was comprised of known PFCs, indicating the need for further investigation to identify unknown fluorinated compounds in wildlife.

Abstract  The production, use, environmental fate, occurrence, and toxicity of perfluoroalkylated substances have been reviewed. Although only a limited number of essential physicochemical data are available, thus hampering a complete assessment of the environmental fate of PFAS, it has become clear that PFAS behave differently from other nonpolar organic micropollutants. PFAS are present in environmental media in urbanized areas both with and without fluorochemicals production sites. The presence of PFOS at levels above the limit of detection has been demonstrated in almost all organisms sampled in a global survey as well as in both nonexposed and exposed human populations. The acute and chronic ecotoxicity of PFOS, PFOA, and 8:2 FTOH to aquatic organisms is moderate to low. Acute toxicity to rodents is also low. PFOS concentrations in effluents have been reported that approach indicative target values derived from available aquatic toxicity data. PFOA has been found to be weakly carcinogenic. This review shows the importance of the perfluoroalkylated substances for the environment and the necessity to fill the current gaps in knowledge of their environmental fate and effects.

Abstract  In this study, the presence of 18 perfluorinated compounds was investigated in biota and environmental samples from the Antarctica and Tierra de Fuego, which were collected during a sampling campaign carried out along February and March 2010. 61 samples were analysed including fish, superficial soils, guano, algae, dung and tissues of Papua penguin by liquid chromatography coupled to tandem mass spectrometry. The concentrations of PFCs were ranging from 0.10 to 240 ng/g for most of the samples except for penguin dung, which presented levels between 95 and 603 ng/g for perfluorooctane sulfonate, and guano samples from Ushuaia, with concentration levels of 1190-2480 ng/g of perfluorohexanoic acid. PFCs acids presented, in general, the highest levels of concentration and perfluorooctanesulfonate was the most frequently found compound. The present study provides a significant amount of results, which globally supports the previous studies, related to the transport, deposition, biodegradation and bioaccumulation patterns of PFCs.

Abstract  Per- and poly-fluorinated compounds (PFCs), which include perfluorinated carboxylates (PFCAs) and sulfonates (PFSAs) and various precursors, are used in a wide variety of industrial, commercial and domestic products. This includes aqueous film forming foam (AFFF), which is used by military and commercial airports as fire suppressants. In a preliminary assessment prior to this study, very high concentrations (>1 ppm wet weight) of the PFSA, perfluorooctane sulfonate (PFOS), were discovered in the plasma of snapping turtles (Chelydra serpentina) collected in 2008 from Lake Niapenco in southern Ontario, Canada. We presently report on a suite of C(6) to C(15) PFCAs, C(4), C(6), C(8) and C(10) PFSAs, several PFC precursors (e.g. perfluorooctane sulfonamide, PFOSA), and a cyclic perfluorinated acid used in aircraft hydraulic fluid, perfluoroethylcyclohexane sulfonate (PFECHS) in surface water from the Welland River and Lake Niapenco, downstream of the John C. Munro International Airport, Hamilton, Ontario, Canada. Amphipods, shrimp, and water were sampled from the Welland River and Lake Niapenco, as well as local references. The same suite of PFCs in turtle plasma from Lake Niapenco was compared to those from other southern Ontario sites. PFOS dominated the sum PFCs in all substrates (e.g., >99% in plasma of turtles downstream the Hamilton Airport, and 72.1 to 94.1% at all other sites). PFOS averaged 2223(±247.1SE) ng/g in turtle plasma from Lake Niapenco, and ranged from 9.0 to 171.4 elsewhere. Mean PFOS in amphipods and in water were 518.1(±83.8)ng/g and 130.3(±43.6) ng/L downstream of the airport, and 19.1(±2.7) ng/g and 6.8(±0.5) ng/L at reference sites, respectively. Concentrations of selected PFCs declined with distance downstream from the airport. Although there was no known spill event or publicly reported use of AFFF associated with a fire event at the Hamilton airport, the airport is a likely major source of PFC contamination in the Welland River.

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  A laboratory investigation on the biotransformation of 8:2 fluorotelomer stearate monoester (8:2 FTS) in aerobic soils was conducted by monitoring the loss of 8:2 FTS, production of 8:2 fluorotelomer alcohol (8:2 FTOH) and stearic acid, which would be released by cleavage of the ester linkage, and subsequent degradation products from FTOH for 80 d. Soil microcosms were extracted with ethyl acetate followed by two heated 90/10 v/v acetonitrile/200 mM NaOH extractions. 8:2 FTS was degraded with an observed half-life (t(1/2)) of 10.3 d. The rate of 8:2 FTS biotransformation substantially decreased after 20 d with 22% of 8:2 FTS still remaining on day 80. No biotransformation of 8:2 FTS occurred in autoclaved soil controls, which remained sterile with 102 ± 6% recovery, through day 20. 8:2 FTOH was generated with cleavage of the ester linkage of 8:2 FTS followed by a rapid decline (t(1/2) ~ 2 d) due to subsequent biodegradation. All the expected 8:2 FTOH degradation products were detected including 8:2 fluorotelomer unsaturated and saturated carboxylic acids, 7:2s FTOH, 7:3 acid, and three perfluoroalkyl carboxylic acids with the most prominent being perfluorooctanoic acid (PFOA). PFOA consistently increased over time reaching 1.7 ± 0.07 mol % by day 80. Although cleavage of the ester linkage was evidenced by 8:2 FTOH production, an associated trend in stearic acid concentrations was not clear because of complex fatty acid metabolism dynamics in soil. Further analysis of mass spectrometry fragmentation patterns and chromatography supported the conclusion that hydrolysis of the ester linkage is predominantly the first step in the degradation of 8:2 FTS with the ultimate formation of terminal products such as PFOA.

Abstract  A single ip injection of perfluoro-n-decanoic acid (PFDA) to male Wistar rats resulted in an initially rapid, then gradual decrease in food consumption and a parallel loss of body weight. Body temperatures and resting heart rates were significantly depressed by PFDA treatment. As early as 12 h following a single dose of PFDA, serum thyroxine (T4) levels were significantly reduced and remained depressed throughout the 8 day study. Serum triiodothyronine (T3) was reduced by 35% 12 h following PFDA treatment and remained at that level throughout the study. These preliminary data suggest that an action on the thyroid axis may be an early primary response to PFDA and that some of the observed subsequent effects may in part be secondary to the change in thyroid hormone levels.

Abstract  Elimination in urine and feces was compared between four perfluorinated fatty acids (PFCAs) with different carbon chain length. In male rats, perfluoroheptanoic acid (PFHA) was rapidly eliminated in urine with the proportion of 92% of the dose being eliminated within 120 h after an intraperitoneal injection. Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) was eliminated in urine with the proportions of 55, 2.0 and 0.2% of the dose, respectively. By contrast, four PFCAs were eliminated in feces with the proportion of less than 5% of the dose within 120 h after an injection. In female rats, the proportions of PFOA and PFNA eliminated in urine within 120 h were 80% and 51% of the dose, respectively, which were significantly higher compared with those in male rats. There was the tendency that PFCA with longer carbon chain length is less eliminated in urine in both male and female rats. Fecal elimination of PFCAs was not different between PFCAs in female rats and comparable to those in male rats. The rates of biliary excretion of PFCAs in male rats were slower than those in female rats. Sex-related difference in urinary elimination of PFOA was abolished when male rats had been castrated. On the contrary, treatment with testosterone suppressed the elimination of PFOA in urine in both castrated male rats and female rats. The effect of testosterone was in a time- and dose-dependent manner. These results suggest that PFCAs are distinguished by their carbon chain length by a renal excretion system, which is regulated by testosterone.

Abstract  The effects of exposure concentration on the bioaccumulation of four perfluorinated chemicals (PFCs): perfluorooctanesulfonate (PFOS), perfluoroocanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), was investigated using green mussels, Perna viridis. Mussels were exposed to concentrations of 1 μgL(-1) and 10 μgL(-1) of each PFC for 56 days, and the bioaccumulation factors (BAF) were found to range from 15 to 859 L/kg and from 12 to 473 L/kg at 1 μgL(-1) and 10 μgL(-1), respectively. For all compounds, the BAF was larger at the lower dosage. Results suggest that the bioaccumulation of PFCs is concentration dependent. This concentration dependency can be explained by a nonlinear adsorption mechanism, which was further supported by the experimental results. The sensitivity of BAF to exposure concentration was found to be positively related to perfluorinated chain length and the binding affinity of the compounds. Bioaccumulation of long chain carboxylates and sulfonates are more easily affected by concentration changes. The validity of the conventional kinetic method was examined by comparing the results with the fundamental steady-state method: in addition to the above-mentioned batch test, mussels were also subject to 24-day exposure (1 μgL(-1) and 10 μgL(-1)) followed by 24-day depuration. Contradictions were found in the resulting kinetic BAF and model curving fittings. A new kinetic model based on adsorption mechanism was proposed, which potentially provide more accurate description of the bioaccumulation process of PFCs.

Abstract  Two perfluorinated surfactants, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were evaluated for their toxicity to the aquatic midge, Chironomus tentans. Impetus for this laboratory study originated from a 10-d, in situ field assessment in which C. tentans was exposed to PFOS at concentrations ranging from 300 to 30,000 microg/L. No midges survived these exposures. Midge survival in a preliminary, acute 10-d laboratory test with nominal PFOS concentrations ranging from 0.1 to 100,000 microg/L showed similar toxicity with respect to survival (median lethal concentration [LC50], 45.2 microg/L) and growth (median effective concentration [EC50], 27.4 microg/L). A parallel test using PFOA indicated no significant impacts on survival or growth. A definitive 10-d assay with PFOS concentrations ranging from 1 to 150 microg/L produced an EC50 for growth (87.2+/-11.6 microg/L) of the same order of magnitude as that in the preliminary findings. The same was not true for survival, however, with the LC50 falling outside the range of test concentrations. To further investigate the sensitivity of C. tentans to PFOS, we conducted a chronic life-cycle test using a nominal concentration range of 1 to 100 microg/L. Three of the four endpoints measured-survival, growth, and emergence-were significantly affected, with EC50 values of 92.2+/-3.1, 93.8+/-2.6, and 94.5+/-3.2 microg/L, respectively. Reproduction was not affected by those PFOS concentrations at which females emerged. The results of the present study indicate that PFOS toxicity thresholds for C. tentans are as much as three orders of magnitude lower than those reported for other aquatic organisms but, at present, are approximately two orders of magnitude higher than those concentrations typically observed in aquatic environments.

Abstract  Twenty high-volume air samples were collected during a crossing of the North Atlantic and Canadian Archipelago in July 2005 to investigate air concentrations of fluorotelomer alcohols (FTOHs) and perfluoalkyl sulfonamido ethanols (PFASs). These commercial chemicals are widely used as surface treatments and are believed to be precursors for perfluorocarboxylic acids (PFCAs) and perfluorooctane sulfonate (PFOS) that accumulate in humans and biota, including those from remote arctic regions. The highest concentrations (sum of gas- and particle-phase) of FTOHs were for 8:2 FTOH (perfluoroctyl ethanol) (5.8-26 pg/m(3)), followed by 10:2 FTOH (perfluorodecyl ethanol) (1.9-17 pg/ m(3)) and 6:2 FTOH (perfluorohexyl ethanol) [BDL (below detection limit) to 6.0 pg/m(3)]. For the PFASs, MeFOSE (N-methyl perfluorooctane sulfonamido ethanol) was dominant and ranged from 2.6 to 31 pg/m(3); EtFOSE (N-ethyl perfluorooctane sulfonamido ethanol) ranged from BDL to 8.9 pg/m(3) and MeFOSEA (N-methyl perfluorooctane sulfonamide ethylacrylate) was BDL in all samples. Air parcel back-trajectories showed that the sampled air was largely representative of the arctic air mass. Air concentrations of target compounds were of the same order of magnitude as reported air concentrations in source regions. For instance, the mean 8:2 FTOH concentration was only a factor of about 3 lower than for three urban samples that were collected in Toronto for comparison. These findings confirm model results that predictthe efficient, long-range atmospheric transport and widespread distribution of FTOHs and related compounds in the arctic region. Mean particulate percentages for FTOHs and PFASs in the cruise samples (mean temperature, 5+/-4 degrees C) were BDL for 6:2 FTOH, 23% for 8:2 FTOH, 15% for 10:2 FTOH, 32% for MeFOSE, and 22% for EtFOSE. Further, the partitioning to particles for MeFOSE and EtFOSE was significantly correlated with inverse absolute temperature, whereas the FTOHs did not show this trend. The Toronto samples (mean temperature, -1+/-1 degree C) showed similar particulate percentages for MeFOSE and EtFOSE; however, the FTOHs were substantially less particle-bound. Although the mechanism for this partitioning is not understood, the results do indicate the need to better account for particle phase transport when modeling the atmospheric fate of these chemicals.

Abstract  Background: Perfluorooctanoate (PFOA) is a synthetic chemical widely detectable in blood of nonoccupationally exposed persons. Its human health effects are not well-characterized. Methods: We conducted a mortality study in a cohort of 3993 employees of an ammonium perfluorooctanoate (APFO) manufacturing facility. APFO rapidly dissociates to PFOA in blood. We estimated standardized mortality ratios (SMRs) compared with the general population, and fit time-dependent Cox regression models to estimate the risks using an internal-cohort referent population. A priori diseases of interest were liver, pancreatic, prostate, and testicular cancer; cirrhosis of the liver; and cerebrovascular disease. Results: APFO exposure was not associated with liver, pancreatic or testicular cancer or with cirrhosis of the liver. SMRs (95% CI) for prostate cancer with no, probable and definite exposure strata were 0.4 (0.1–0.9), 0.9 (0.4–1.8), and 2.1 (0.4–6.1), respectively, and for cerebrovascular disease 0.5 (0.3–0.8), 0.7 (0.4–1.1), and 1.6 (0.5–3.7), respectively. The diabetes SMR for probable exposure was 2.0 (1.0–3.2). Compared with an internal referent population of nonexposed workers, moderate or high exposures to ammonium perfluorooctanoate were positively associated with prostate cancer (HR = 3.0 [0.9–9.7] and 6.6 [1.1–37.7], respectively) and with cerebrovascular disease (1.8 [0.9–3.1] and 4.6 [1.3–17.0], respectively). Diabetes was associated with moderate exposure 3.7 (1.4–10.1); no deaths from diabetes occurred in workers with high exposure. Conclusion: We did not observe ammonium perfluorooctanoate exposure to be associated with liver, pancreatic, and testicular cancer or cirrhosis of the liver. Exposure was associated (albeit inconsistently) with prostate cancer, cerebrovascular disease, and diabetes.

Abstract  BACKGROUND: Polyfluoroalkyl chemicals (PFCs) have been widely used in consumer products. Exposures in the United States and in world populations are widespread. PFC exposures have been linked to various health impacts, and data in animals suggest that PFCs may be potential developmental neurotoxicants.

OBJECTIVES: We evaluated the associations between exposures to four PFCs and parental report of diagnosis of attention deficit/hyperactivity disorder (ADHD).

METHODS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2003-2004 for children 12-15 years of age. Parental report of a previous diagnosis by a doctor or health care professional of ADHD in the child was the primary outcome measure. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) levels were measured in serum samples from each child.

RESULTS: Parents reported that 48 of 571 children included in the analysis had been diagnosed with ADHD. The adjusted odds ratio (OR) for parentally reported ADHD in association with a 1-μg/L increase in serum PFOS (modeled as a continuous predictor) was 1.03 [95% confidence interval (CI), 1.01-1.05]. Adjusted ORs for 1-μg/L increases in PFOA and PFHxS were also statistically significant (PFOA: OR = 1.12; 95% CI, 1.01-1.23; PFHxS: OR = 1.06; 95% CI, 1.02-1.11), and we observed a nonsignificant positive association with PFNA (OR = 1.32; 95% CI, 0.86-2.02).

CONCLUSIONS: Our results, using cross-sectional data, are consistent with increased odds of ADHD in children with higher serum PFC levels. Given the extremely prevalent exposure to PFCs, follow-up of these data with cohort studies is needed.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM ABSTRACT ALUMINUM CLOFIBRATE SIMFIBRATE DIETHYLHEXYL PHTHALATE CARCINOGENESIS 8 HYDROXYDEOXYGUANOSINE PERFLUOROOCTANOIC ACID PERFLUORODECANOIC ACID

Abstract  BACKGROUND: Perfluoroalkyl acids are persistent compounds used in various industrial -applications. Of these compounds, perfluorooctanoate (PFOA) is currently detected in humans worldwide. A recent study on low-dose developmental exposure to PFOA in mice reported increased weight and elevated biomarkers of adiposity in postpubertal female offspring.

OBJECTIVE: We examined whether the findings of increased weight in postpubertal female mice could be replicated in humans.

METHODS: A prospective cohort of 665 Danish pregnant women was recruited in 1988-1989 with offspring follow-up at 20 years. PFOA was measured in serum from gestational week 30. Offspring body mass index (BMI) and waist circumference were recorded at follow-up (n = 665), and biomarkers of adiposity were quantified in a subset (n = 422) of participants.

RESULTS: After adjusting for covariates, including maternal pre-pregnancy BMI, smoking, education, and birth weight, in utero exposure to PFOA was positively associated with anthropometry at 20 years in female but not male offspring. Adjusted relative risks comparing the highest with lowest quartile (median: 5.8 vs. 2.3 ng/mL) of maternal PFOA concentration were 3.1 [95% confidence interval (CI): 1.4, 6.9] for overweight or obese (BMI ≥ 25 kg/m2) and 3.0 (95% CI: 1.3, 6.8) for waist circumference > 88 cm among female offspring. This corresponded to estimated increases of 1.6 kg/m2 (95% CI: 0.6, 2.6) and 4.3 cm (95% CI: 1.4, 7.3) in average BMI and waist circumference, respectively. In addition, maternal PFOA concentrations were positively associated with serum insulin and leptin levels and inversely associated with adiponectin levels in female offspring. Similar associations were observed for males, although point estimates were less precise because of fewer observations. Maternal perfluorooctane sulfonate (PFOS), perfluorooctane sulfonamide (PFOSA), and perfluorononanoate (PFNA) concentrations were not independently associated with offspring anthropometry at 20 years.

CONCLUSIONS: Our findings on the effects of low-dose developmental exposures to PFOA are in line with experimental results suggesting obesogenic effects in female offspring at 20 years of age.

Abstract  Flow cytometric measurements were used to investigate the toxic effect of perfluorobutanoic sulfonate (PFBS), perfluorooctane sulfonate (PFOS), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorododecanoic acid (PFDoA), and perfluorotetradecanoic acid (PFTeA) on some membrane systems of the freshwater alga species Scenedesmus obliquus. Among the test compounds, PFOS, PFDoA, and PFTeA inhibited algal growth rate in a concentration-dependent manner while PFBS, PFHxA, and PFOA did not inhibit algal growth within the test concentration ranges. An enhancement of the mitochondrial membrane potential (MMP) and cell membrane permeability in S. obliquus was observed caused by exposure to PFOS, PFOA, PFDoA, and PFTeA. Both carbon chain length and acid group influenced the toxicity of PFAAs, where the toxicity increased with increasing carbon chain length for the compounds belonging to the same class. The observed effective concentrations lie in the micromole range and the test compounds disrupted membrane properties at concentrations below those associated with algal growth inhibition. Flow cytometry is proved to be a useful technique for toxicity testing with microalgae and provide additional information regarding the mode of action of PFAAs to algal species.

Abstract  The quantitative measurement of individual cells and their characteristics by means of flow cytometry is already for many years of great value for clinical studies. However, its potential as a tool in (eco)toxicology has only recently been discovered. Analysis of cell cycle kinetics with DNA-staining dyes can offer a valuable alternative to detect effects of chemicals on cell proliferation, an important endpoint in screening estrogen-like properties of chemicals. In the present study, flow cytometric cell cycle analysis in growth arrested MCF-7 cells exposed to five xenoestrogens correspond well with cell proliferation results of the conventionally used E-screen assay. Moreover, re-induction of proliferation in MCF-7 cells, indicated by the percentage of cells in S(ynthesis)-phase, is most pronounced after 24 h exposure, thus allowing a faster screening of xenoestrogens. This flow cytometric proliferation assay confirms that the estrogenic activity of structurally analogous parabens is mediated by the estrogen receptor pathway and is proportional to the alkyl chain length. Moreover, the ER-mediated mode of action of two fluorotelomer alcohols (6:2 FTOH and 8:2 FTOH), recently reported as xenoestrogenic, could be elucidated. These results support the potential of flow cytometric cell cycle kinetics as a screening assay for estrogen-like properties of chemicals.

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  Perfluorononanoic acid (PFNA), a synthetic perfluorinated carboxylic acid and fluorosurfactant, is a known environmental contaminant found in people and wildlife. To understand the hepatotoxicity mechanism of PFNA, male zebrafish (n=200) were exposed to differing concentrations of PFNA (0, 0.1, 0.5, and 1.0 mg/L) for 180 days. A two-dimensional difference gel electrophoresis (2-D DIGE) approach coupled with MALDI-TOF-MS/MS analysis was employed to detect and identify the differential expressed proteins. A total of 57 proteins were successfully identified and categorized into functional classes that included metabolism (amino acid metabolism, TCA cycle and pyruvate metabolism, gluconeogenesis and glycolysis, protein metabolism and modification, and nucleotides metabolism), structure and motility, stress and defense, signal transduction, and cell communication. Our proteomic analyses added new perspective to PFNA hepatotoxicity in zebrafish. Results regarding mRNA levels demonstrated that the involvement of peroxisome proliferator-activated receptors (PPARs) could not sufficiently explain the hepatotoxicity mechanism of PFAAs in zebrafish. The extensive protein variations indicated that multiple cellular pathways were involved in and suggested that multiple protein molecules should be simultaneously targeted as an effective strategy to counter PFNA toxicity. Other potential modes should be further investigated.

Abstract  PURPOSE: Samples from the German Environmental Specimen Bank (ESB) covering particularly the years 1994-1996, 2000-2002, and 2006-2009 were analyzed for perfluorinated compounds (PFC; mainly C4-C13 carboxylic and sulfonic acids) to gain an overview on current PFC levels and patterns in marine, limnetic, and terrestrial biota; to assess their concentrations in different trophic levels; and to investigate whether risk management measures for PFC are successful.

METHODS: Specimens, either standardized annual pooled samples (blue mussels, eelpout liver, bream liver, pigeon eggs) or individual single samples (cormorant eggs, rook eggs), were collected for the German ESB program from representative sampling sites according to documented guidelines. After appropriate extraction, PFC were quantified under ISO/IEC 17025 accreditation by HPLC/MS-MS with isotopically labeled internal standards. Limits of quantification (LOQs) were 0.2-0.5 ng/g. Data are reported on a wet weight basis.

RESULTS AND DISCUSSION: In most samples the predominant PFC was perfluorooctane sulfonic acid (PFOS). However, in marine mussels from North and Baltic Seas, PFOS levels were mostly below the LOQ, but low residues of PFOS amide were found which declined in recent years. Livers of eelpout showed maximum concentrations of 15-25 ng/g PFOS in the period 2000-2002 and low amounts of perfluoropentanoate in all years. Beside PFOS (median 48 ng/g) several PFC could be determined in cormorant eggs sampled in 2009 from a Baltic Sea site. For a freshwater ecosystem, current PFC burdens for cormorant eggs were even higher (median 400 ng/g PFOS). Livers of bream from rivers showed concentrations of 130-260 ng/g PFOS, but for bream from a reference lake levels were only about 6 ng/g. In contrast to cormorants, eggs of rook and feral pigeon from terrestrial ecosystems displayed only low PFC burdens (up to 6 ng/g PFOS).

CONCLUSIONS: Generally, PFC levels were lower in marine than in freshwater biota. PFC burdens were higher in biota from the ESB-North Sea sites than in Baltic Sea organisms. Levels of PFC were quite high especially in top predators of both limnetic and marine ecosystems. Only low PFC levels were detected in eggs of terrestrial birds. A decrease of PFOS levels from maximum values around the year 2000 observed at least in North Sea biota may be a result of a production cease and shifts in marketing pattern.

Abstract  Recently, polyfluorinated and perfluorinated compounds (PFCs) have been detected in most surface waters around the world. Because some PFCs are persistent and tend to accumulate in surface waters, their potential adverse effects to aquatic organisms have received increasing attention. Nevertheless, currently available toxicity information is limited. The aim of this study was to evaluate the toxicity effects of seven PFCs on root elongation of lettuce (Lactuca sativa) and photosynthesis of green algae (Pseudokirchneriella subcapitata). It was found that the toxicity profiles of both species tested were similar and had good relations with the fluorinated carbon-chain length of the PFCs investigated. One of the compounds tested, perfluorobutanoic acid, was found to be more toxic than expected in the algae test, which may be related with acidification of the test solution. It was concluded that because short-chained PFCs are becoming the predominant PFC pollutants in surface waters, their long-term toxicity and mixture toxicity with other PFCs should be studied in greater detail.