Abstract  IMAC can be used to selectively enrich phosphopeptides from complex peptide mixtures, but co-retention of acidic peptides together with the failure to retain some phosphopeptides restricts the general utility of the method. In this study Fe(III)-IMAC was qualitatively and quantitatively assessed using a panel of phosphopeptides, both synthetic and derived from proteolysis of known phosphoproteins, to identify the causes of success and failure in the application of this technique. Here we demonstrate that, as expected, peptides with a more acidic amino acid content are generally more efficiently purified and detected by MALDI-MS after Fe(III)-IMAC than those with a more basic content. Modulating the loading buffer used for Fe(III)-IMAC significantly affects phosphopeptide binding and suggests that conformational factors that lead to steric hindrance and reduced accessibility to the phosphate are important. The use of 1,1,1,3,3,3-hexa-fluoroisopropanol is shown here to significantly improve Fe(III)-IMAC enrichment and subsequent detection of phosphopeptides by MALDI-MS.

Abstract  #311 chemicals were tested under code, for mutagenicity, in Salmonella typhimurium; 35 of the chemicals were tested more than once in the same or different laboratories. The tests were conducted using a preincubation protocol in the absence of exogenous metabolic activation, and in the presence of liver S-9 from Aroclor-induced male Sprague-Dawley rats and Syrian hamsters. Some of the volatile chemicals were also tested in desiccators. A total of 120 chemicals were mutagenic or weakly mutagenic, 3 were judged questionable, and 172 were non-mutagenic. The remaining 16 chemicals produced different responses in the two or three laboratories in which they were tested. The results and data from these tests are presented.

Abstract  4,4-Methylenediphenyl diisocyanate (MDI) is a very important component in the production of polyurethane. In a long-term experiment, designed to determine the carcinogenic and toxic effects of MDI, rats were exposed chronically for 3 and 12 months, to 0.0 (control), 0.26, 0.70 and 2.06 mg MDI/m(3) as aerosols. Hemoglobin adducts and urine metabolites of MDI were determined at the different doses in order to develop methods to biomonitor workers exposed to MDI and to assess a risk resulting from such exposure. Hemoglobin adducts and urine metabolites of 4,4-methylenedianiline (MDA) were found in all rats, including controls. MDA and N-acetyl-MDA (AcMDA) Were quantified by GC-MS after derivatization with heptafluorobutyric anhydride. The dose-response relationships for hemoglobin adducts and urine metabolites were non-linear over this dose range. In urine, free AcMDA and MDA were found after base extraction. The amount of MDA present in urine and to a lesser extent the AcMDA found in urine correlate well with the corresponding amount determined as hemoglobin adducts for all dose groups. In order to release MDA from possible conjugates of MDA and AcMDA, urine was treated under strong acidic conditions. Following this procedure higher MDA levels were found than the sum of MDA and AcMDA from mild base hydrolysis, Similar results were obtained with the rats exposed for 3 and 12 months, indicating that a steady state had been reached by 3 months. In order to perform further investigations of the bronchoalveolar lavage fluid one group of animals was given a 1 week recovery period before sacrifice, Hemoglobin adducts from these animals showed a decrease of approximately 40% for all dose groups. According to the lifetime of rat erythrocytes the levels of hemoglobin adducts should have decreased by only 22%. This suggests that the erythrocytes with modified hemoglobin have a shorter lifespan. In order to exclude the possibility that hemoglobin adducts may have resulted from ingestion of hydrolyzed MDI via licking of the fur, a single dose experiment with rats exposed through the nose only or with the whole body was carried out. The only difference observed between these two exposure regimes was that the hemoglobin adduct levels of AcMDA after nose only exposure were significantly higher than after total body exposure. The presence of AcMDA in urine and as a hemoglobin adduct indicates that MDA was bioavailable after MDI exposure. The presence of MDA may contribute significantly to the carcinogenic potential of MDI, since MDA has been shown to be carcinogenic in animals.

Abstract  Perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) have been detected globally in wildlife and humans. Data from a gene array indicate that PFOA decreases organic anion transporting polypeptides (Oatps) in liver. Na(+)-taurocholate cotransporting polypeptide (Ntcp) and Oatp1a1, 1a4, and 1b2 are major transporters responsible for uptake of bile acids (BAs) and other organic compounds into liver. The purpose of the present study was to determine the effects of two perfluorinated fatty acids, PFOA and PFDA, on mRNA and protein expression of hepatic uptake transporters Oatps and Ntcp, and to determine the underlying regulatory mechanisms by using peroxisome proliferator-activated receptor alpha (PPAR-alpha), constitutive androstane receptor, pregnane-X receptor, NF-E2-related factor 2, and farnesoid X receptor-null mouse models. After 2 days following a single i.p. administration, PFOA did not alter serum BA concentrations, but PFDA increased serum BA concentrations 300%. Furthermore, PFOA decreased mRNA and protein expression of Oatp1a1, 1a4, and 1b2, but not Ntcp in mouse liver. In contrast, PFDA decreased mRNA and protein expression of all four transporters, and decreased the mRNA expression in a dose-dependent manner, with the decrease of Oatp1a4 occurring at lower doses than the other three transporters. Multiple mechanisms are likely involved in the down-regulation of mouse Oatps and Ntcp by PFDA. By using the various transcription factor-null mice, PPAR-alpha was shown to play a central role in the down-regulation of Oatp1a1, 1a4, 1b2, and Ntcp by PFDA. The current studies provide important insight into understanding the mechanisms by which PFDA regulate the expression of hepatic uptake transporters. In conclusion, PFOA and PFDA decrease mouse liver uptake transporters primarily via activation of PPAR-alpha.

Abstract  A wide variety of compounds, including hypolipidemic drugs, plasticizers and other industrial chemicals, have been found to cause liver enlargement and hepatic peroxisome proliferation by mechanisms that are unclear. Although thyroid and sex hormones have been shown to modulate the hepatic response to these chemicals, the role of adrenal hormones in these phenomena is not clear, and a few studies have produced conflicting data. Therefore this study was undertaken to investigate the role of adrenal hormones in hepatomegaly and peroxisomal enzyme induction caused by peroxisomal proliferators and to further delineate the interrelationship between these parameters. Because adrenalectomy alters hepatic drug metabolism, we have used the nonmetabolizable proliferator perfluorooctanoic acid. Our data show that hepatomegaly caused by perfluorooctanoic acid depends on corticosterone, the major glucocorticoid in rodents. Liver growth caused by perfluorooctanoic acid appears to be predominantly hypertrophic in nature, and DNA synthesis in response to perfluorooctanoic acid predominates in periportal regions of the liver lobule. Data also show that although induction of peroxisomal beta-oxidation by perfluorooctanoic acid is independent of adrenal hormones, induction of catalase is dependent on the presence of these hormones. This study supports the contention that induction of activities of various peroxisomal enzymes is controlled by different regulatory mechanisms.

Abstract  Macrophage activation contributes to adverse effects produced by a number of hepatotoxic compounds. Transcriptional profiles elicited by two macrophage activators, LPS and zymosan A, were compared to those produced by 100 paradigm compounds (mostly hepatotoxicants) using cDNA microarrays. Several hepatotoxicants previously reported to activate liver macrophages produced transcriptional responses similar to LPS and zymosan, and these were used to construct a gene signature profile for macrophage activators in the liver. Measurement of cytokine mRNAs in the same liver samples by RT-PCR independently confirmed that these compounds are associated with macrophage activation. In addition to expected effects on acute phase proteins and metabolic pathways that are regulated by LPS and inflammation, a strong induction was observed for many endoplasmic reticulum-associated stress/chaperone proteins. Additionally, many genes in our macrophage activator signature profile were well-characterized PPARalpha-induced genes which were repressed by macrophage activators. A shared gene signature profile for peroxisome proliferators was determined using a training set of clofibrate, WY 14643, diethylhexylphthalate, diisononylphthalate, perfluorodecanoic acid, perfluoroheptanoic acid, and perfluorooctanoic acid. The signature profile included macrophage activator-induced genes that were repressed by peroxisome proliferators. NSAIDs comprised an interesting pharmacological class in that some compounds, notably diflunisal, co-clustered with peroxisome proliferators whereas several others co-clustered with macrophage activators, possibly due to endotoxin exposure secondary to their adverse effects on the gastrointestinal system. While much of these data confirmed findings from the literature, the transcriptional patterns detected using this toxicogenomics approach showed relationships between genes and biological pathways requiring complex analysis to be discerned.

Abstract  Two specific amino acid residues in transmembrane segments (TM) 2 and 3 are critical for the enhancement of glycine receptor (GlyR) function by volatile anesthetics. To determine which physicochemical characteristics of these sites determine their roles in anesthetic actions, an extensive series of single amino acid mutations at amino acid residue 288 (Ala-288) in TM3 of the alpha1 GlyR subunit was tested for modulation by volatile anesthetics. The mutations changed the apparent affinities of receptors for glycine; replacements with larger volumes and less hydropathy exhibited higher affinities for glycine. Potentiation by anesthetics was reduced by specific mutations at Ala-288. The molecular volume of the substituents was negatively correlated with the extent of potentiation by isoflurane, enflurane, and 1-chloro-1,2,2-trifluorocyclobutane, whereas there was no correlation between anesthetic enhancement and polarity, hydropathy, or hydrophilicity of substituents. In contrast to anesthetics, no correlation was found between the effects of the nonanesthetics 1,2-dichlorohexafluorocyclobutane or 2, 3-dichlorooctafluorobutane and any physicochemical property of the substituent. These results suggest that the molecular volume and hydropathy of the amino acid at position 288 in TM3 regulate glycine and anesthetic sensitivity of the GlyR and that this residue might represent one determinant of an anesthetic binding site

Abstract  A general multimedia environmental fate model is presented that is capable of simulating the fate of up to four interconverting chemical species. It is an extension of the existing equilibrium criterion (EQC) fugacity model, which is limited to single-species assessments. It is suggested that multispecies chemical assessments are warranted when a degradation product of a released chemical is either more toxic or more persistent than the parent chemical or where there is cycling between species, as occurs with association, disassociation, or ionization. The model is illustratively applied to three chemicals, namely chlorpyrifos, pentachlorophenol, and perfluorooctane sulfonate, for which multispecies assessments are advisable. The model results compare favorably with field data for chlorpyrifos and pentachlorophenol, while the perfluorooctane sulfonate simulation is more speculative due to uncertainty in input parameters and the paucity of field data to validate the predictions. The model thus provides a tool for assessing the environmental fate and behavior of a group of chemicals that hitherto have not been addressed by evaluative models such as EQC.

Abstract  Wyeth-14,643 (WY) and ammonium perfluorooctanoate (C8) belong to a diverse class of compounds which have been shown to produce hepatic peroxisome proliferation in rodents. From previous work, WY, but not C8, has been shown to produce hepatocellular carcinoma in rats, while C8 has been shown to produce Leydig cell adenomas. In addition, based on a review of bioassay data a relationship appears to exist between peroxisome-proliferating compounds and Leydig cell adenoma and pancreatic acinar cell hyperplasia/adenocarinoma formation. To further investigate the relationship between peroxisome-proliferating compounds and hepatic, Leydig cell, and pancreatic acinar cell tumorigenesis, a 2-year feeding study in male CD rats was initiated to test the hypothesis that peroxisome proliferating compounds induce a tumor triad (liver, Leydig cell, pancreatic acinar cell), and to examine the potential mechanism for the Leydig cell tumors. The study was conducted using 50 ppm WY and 300 ppm C8. The concentration of WY in the diet was decreased to 25 ppm on test day 301 due to increased mortality. In addition to the ad libitum control, a second control was pair-fed to the C8 group. Interim sacrifices were performed at 1- or 3-month intervals. Peroxisome proliferation measured by β-oxidation activity and cell proliferation were measured in the liver and testis at all time points and in the pancreas beginning at the 9-month time point (cell proliferation only). Serum hormone concentrations (estradiol, testosterone, LH, FSH, and prolactin) were also measured at each time point. Increased relative liver weights and hepatic β-oxidation activity were observed in both the WY- and C8-treated rats at all time points. In contrast, hepatic cell proliferation was significantly increased only in the WY-treated group. Neither WY nor C8 significantly altered the rate of Leydig cell β-oxidation or Leydig cell proliferation when compared to the control groups. Moreover, the basal rate of β-oxidation in Leydig cells was approximately 20 times less than the rate of hepatic β-oxidation. There were no biologically meaningful differences in serum testosterone, FSH, prolactin, or LH concentrations in the WY- and C8-treated rats when compared to their respective controls. There were, however, significant increases in serum estradiol concentrations in the WY- and C8-treated rats at 1, 3, 6, 9, 15, 18, and 21 months. At 12 months, only the C8-treated rats had elevated serum estradiol concentrations when compared to the pair-fed control. Histopathological evaluation revealed compound-related increases in liver, Leydig cell, and pancreatic acinar cell tumors in both WY- and C8-treated rats. The data support the hypothesis that the peroxisome-proliferating compounds induce the previously described tumor triad. In addition, both C8 and WY produced a sustained increase in serum estradiol concentrations that correlated with the potency of the 2 compounds to induce Leydig cell tumors (i.e., WY caused a more consistent sustained increase in serum estradiol throughout the entire study, and more specifically at the end of the study, than did C8). This study suggests that estradiol may play a role in enhancement of Leydig cell tumors in the rat, and that peroxisome proliferators may induce tumors via a non-LH type mechanism.

Abstract  OBJECTIVES: The objective of this article is to extend our previous studies of persistent organic pollutant (POP) contamination of U.S. food by measuring perfluorinated compounds (PFCs), organochlorine pesticides, and polychlorinated biphenyls (PCBs) in composite food samples. This study is part of a larger study reported in two articles, the other of which reports levels of polybrominated diphenyl ethers and hexabromocyclododecane brominated flame retardants in these composite foods [Schecter et al. 2010. Polybrominated diphenyl ethers (PBDEs) and hexabromocyclodecane (HBCD) in composite U.S. food samples, Environ Health Perspect 118:357–362]. METHODS: In this study we measured concentrations of 32 organochlorine pesticides, 7 PCBs, and 11 PFCs in composite samples of 31 different types of food (310 individual food samples) purchased from supermarkets in Dallas, Texas (USA), in 2009. Dietary intake of these chemicals was calculated for an average American. RESULTS: Contamination varied greatly among chemical and food types. The highest level of pesticide contamination was from the dichlorodiphenyltrichloroethane (DDT) metabolite p,p´­dichlorodiphenyldichloroethylene, which ranged from 0.028 ng/g wet weight (ww) in whole milk yogurt to 2.3 ng/g ww in catfish fillets. We found PCB congeners (28, 52, 101, 118, 138, 153, and 180) primarily in fish, with highest levels in salmon (PCB-153, 1.2 ng/g ww; PCB-138, 0.93 ng/g ww). For PFCs, we detected perfluorooctanoic acid (PFOA) in 17 of 31 samples, ranging from 0.07 ng/g in potatoes to 1.80 ng/g in olive oil. In terms of dietary intake, DDT and DDT metabolites, endosulfans, aldrin, PCBs, and PFOA were consumed at the highest levels. CONCLUSION: Despite product bans, we found POPs in U.S. food, and mixtures of these chemicals are consumed by the American public at varying levels. This suggests the need to expand testing of food for chemical contaminants.

Abstract  The biodegradability of several potential endocrine disrupting compounds, namely 4-n-nonylphenol (4-n-NP), nonylphenol monoethoxylate (NP1EO), nonylphenol diethoxylate (NP2EO), bisphenol A (BPA), triclosan (TCS), di-(2-ethylhexyl)-phthalate (DEHP), perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) was evaluated in this study, using OECD method 301F (manometric respirometry test) and activated sludge as inoculum. According to the results, 4-n-NP and BPA meet the strict definition of ready biodegradability and they are not expected to be persistent during the activated sludge process. Partial biodegradation was observed for DEHP (58.7+/-5.7%, n=3), TCS (52.1+/-8.5%, n=3) and NP1EO (25.9+/-8.1%, n=3), indicating their possible biodegradation in wastewater treatment systems, while no biodegradation was observed for NP2EO, PFOA and PFNA. Experiments in the co-presence of a readily biodegradable compound showed the absence of co-metabolic phenomena during 4-n-NP, BPA and TCS biodegradation. Using first order kinetics to describe biodegradation of the target compounds, half-lives of 4.3+/-0.6, 1.3+/-0.2, 1.8+/-0.5, 6.9+/-2.6 days were calculated for 4-n-NP, BPA, TCS and DEHP, respectively. Toxicity tests using marine bacterium Vibrio fischeri showed that biodegradation of 4-n-NP, NP1EO, BPA and TCS is a simultaneous detoxification process, while possible abiotic or biotic transformations of NP2EO, DEHP, PFOA and PFNA during respirometric test resulted to significant increase of their toxicities.

Abstract  Aerosol “sniffing,” a variant of glue “sniffing,” involves the deliberate inhalation of aerosol products and propellants. Approximately 65 deaths have been attributed to this practice. They have been predominantly sudden and generally lack conclusive autopsy findings. The cause of death has not been defined in most cases; however, various mechanisms have been postulated. The evidence suggests acute cardiac arrest as a frequent cause. It could result from the sudden onset of ventricular fibrillation due to sensitization of the heart to epinephrine by inhalation of high concentrations of aerosol contents. Experimental investigation revealed that the commonly used aerosol propellants, in high concentrations, are capable of sensitizing the heart to epinephrine resulting in serious cardiac arrhythmias. Therefore, it is concluded that cardiac sensitization is a likely mechanism of death in many of the aerosol-sniffing fatalities.

Abstract  Selecting the appropriate pharmacokinetic (PK) model given the available data is investigated for perfluorooctanoic acid (PFOA), which has been widely analyzed with an empirical, one-compartment model. This research examined the results of experiments [Kemper R. A., DuPont Haskell Laboratories, USEPA Administrative Record AR-226.1499 (2003)] that administered single oral or iv doses of PFOA to adult male and female rats. PFOA concentration was observed over time; in plasma for some animals and in fecal and urinary excretion for others. There were four rats per dose group, for a total of 36 males and 36 females. Assuming that the PK parameters for each individual within a gender were drawn from the same, biologically varying population, plasma and excretion data were jointly analyzed using a hierarchical framework to separate uncertainty due to measurement error from actual biological variability. Bayesian analysis using Markov Chain Monte Carlo (MCMC) provides tools to perform such an analysis as well as quantitative diagnostics to evaluate and discriminate between models. Starting from a one-compartment PK model with separate clearances to urine and feces, the model was incrementally expanded using Bayesian measures to assess if the expansion was supported by the data. PFOA excretion is sexually dimorphic in rats; male rats have bi-phasic elimination that is roughly 40 times slower than that of the females, which appear to have a single elimination phase. The male and female data were analyzed separately, keeping only the parameters describing the measurement process in common. For male rats, including excretion data initially decreased certainty in the one-compartment parameter estimates compared to an analysis using plasma data only. Allowing a third, unspecified clearance improved agreement and increased certainty when all the data was used, however a significant amount of eliminated PFOA was estimated to be missing from the excretion data. Adding an additional PK compartment reduced the unaccounted-for elimination to amounts comparable to the cage wash. For both sexes, an MCMC estimate of the appropriateness of a model for a given data type, the Deviance Information Criterion, indicated that this two-compartment model was better suited to describing PFOA PK. The median estimate was 142.1 +/- 37.6 ml/kg for the volume of the primary compartment and 1.24 +/- 1.1 ml/kg/h for the clearances of male rats and 166.4 +/- 46.8 ml/kg and 30.3 +/- 13.2 ml/kg/h, respectively for female rats. The estimates for the second compartment differed greatly with gender-volume 311.8 +/- 453.9 ml/kg with clearance 3.2 +/- 6.2 for males and 1400 +/- 2507.5 ml/kg and 4.3 +/- 2.2 ml/kg/h for females. The median estimated clearance was 12 +/- 6% to feces and 85 +/- 7% to urine for male rats and 8 +/- 6% and 77 +/- 9% for female rats. We conclude that the available data may support more models for PFOA PK beyond two-compartments and that the methods employed here will be generally useful for more complicated, including PBPK, models.

Abstract  Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) compounds associated with surface protection product manufactures are distributed globally. The 3-5-year half-lives, reproductive and liver toxicity in animals, and lack of understanding of the factors regulating retention in the body have led to a world-wide public concern for use of these materials. Using a novel physiologically-motivated pharmacokinetic model for renal clearance, perfluoroalkylacid pharmacokinetics in monkeys was successfully described by renal resorption via high efficiency transporters for both intravenous and oral dosing. Intravenous dosing with both PFOA and PFOS in Cynomolgus monkeys produced time course curves consistent with a two-compartment distribution. Extending the PK model for intravenous dosing to examine blood and urine time course data for repeated oral dosing clearly identified the saturable renal resorption. Resorption depends on kinetic factors for transport (T(mC), transport maximum; K(T), transport affinity) and free fraction in plasma (f(plasma)). For PFOA, these parameters were estimated to be 5mg/(h kg) (T(mC)), 0.055 mg/L (K(T)), and 0.02 (f(plasma)). PFOS has longer half-life and had respective values of 13.6 mg/(h kg), 0.023 mg/L, and 0.025. PFOS appeared to have a higher transport capacity and lower affinity than PFOA. Human kinetics indicates even higher resorption efficiency.

Abstract  In this study, octadecyl (C(18)) and aminopropyl group modified titanate nanotubes (C(18)/NH(2)-TNs) were prepared successfully with a silylation method by introducing octadecyltrimethoxysilane (ODS) and aminopropyltrimethoxysilane (APS) simultaneously to the surface of titanate nanotubes (TNs). The properties of the products were characterized in detail. The results indicated that there might be steric hindrance effects to C(18) groups on the nanoscaled interior and exterior space of TNs. Therefore, aminopropyl groups were more ready to immobilize on the surface of TNs than C(18) groups when the organosilanes ODS and APS coexisted in reaction solution. C(18)/NH(2)-TNs with the obvious characteristic of C(18) and aminopropyl groups were obtained as the ratio of ODS/APS in reaction solution was 4.0, and the corresponding proportion of the two groups (C(18)/NH(2)) on the C(18)/NH(2)-TN surface was about 0.25. This adsorbent had good water dispersibility, overcoming the bad deficiency of reverse phase nanosized materials in water and improving its accessibility to polar analytes. Due to the cooperative effect of alkyl and aminopropyl groups coupled with the residual hydroxyl groups on the surface, C(18)/NH(2)-TNs exhibited excellent affinity efficiency to some ionic or ionizable organic analytes under a different solution pH, including anionic (perfluorooctane sulfonate, perfluorooctanoic acid, and sodium dodecyl sulfate), cationic (cetyltrimethylammonium bromide), and amphoteric compounds (sulfamethazine). The selective binding of these anionic, amphoteric, and cationic analytes could be achieved by adjusting solution pH to acid, neutral, and alkaline conditions, respectively. Since C(18)/NH(2)-TNs possessed relatively large surface areas and strong affinity ability to ionic analytes, especially with long alkyl chains, it showed significantly higher adsorption capacity for perfluorooctane sulfonate than activated carbon and anion-exchange resin.

Abstract  Concentrations of 12 perfluorinated compounds (PFCs) were measured in 21 representive water, sediment and soil samples from Guanting Reservoir and vicinity. Perfluorooctanoic acid (PFOA) was the predominant PFCs with concentrations of 0.55-2.3 ng/L, <LOQ to 0.68 ng/g dw and <LOQ to 2.8 ng/g dw in water, sediment and soil, respectively. Perfluorododecanoic acid (PFDoA) was frequently detected in solid matrices, with concentrations of <LOQ to 0.18 ng/g dw in sediment and 0.13-0.26 ng/g dw in soil. PFCs were detected in all environmental matrices sampled, but concentrations found throughout the watershed were less than those reported from other locations.

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.

Abstract  PURPOSE: Due to their high water solubilities and mobilities, persistent, polar perfluorinated compounds (PFCs) such as perfluorinated carboxylates and sulfonates are likely to end up in the oceans. In part 1 of this study, their distribution in North and Baltic Sea water is reported, being of special interest because these seas are surrounded by highly industrialized countries with high population densities.

METHODS: A combination of solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry was used after optimisation to determine nine PFCs with chain lengths of C(4) to C(10) in water samples at ultra-trace levels.

RESULTS: The observed concentration distribution and gradients were explained by oceanographic mixing processes and currents. The big rivers were identified as major input sources. At the mouth of the river Elbe, concentrations of 9 ng/L were observed for perfluorooctanoate (PFOA), and 8 ng/L for perfluorooctylsulfonate (PFOS); all other PFC concentrations ranged from 0.6 to 1.7 ng/L. At coastal stations, concentrations decreased to 3.8 ng/L (PFOA) and 1.8 ng/L (PFOS), dropping to 0.13 and 0.09 ng/L, respectively, towards the open sea. Along the Dutch coast, high perfluorobutylsulfonate concentrations (3.9 ng/L) were observed as regional characteristics. In the Baltic Sea, fairly even PFC distributions with low gradients were observed. Again, PFOA and PFOS were the major compounds (up to 1.1 and 0.9 ng/L).

CONCLUSION: The results underline the necessity to include PFCs in marine monitoring programs. Water was found to be a good matrix for monitoring environmental levels, sources, and transport pathways of PFCs.

Abstract  Perfluorinated alkylated substances (PFAS) are of global interest due to their occurrence and persistency in the environment. This study includes surface waters and sediments for the analysis of eleven PFAS. The PFAS studied can be grouped in perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates (PFS) and perfluoroalkyl sulfonamides (PFSA). The two most important compounds are perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS). These two substances showed the most significant values for surface water samples with maximum concentrations of 21 ng l(-1) for PFOA and 37 ng l(-1) for PFOS. Sediment samples from seven Austrian lakes and the river Danube were studied. Whereas PFSA and PFS were not detected in any sediment sample PFCAs were detected in most of the lake samples in concentrations up to 1.7 microg kg(-1) dry wt. PFOA, perfluorohexanoic acid (PFHxA) and perfluoroheptanoic acid (PFHpA) were detected in all Danube river sediment samples in concentrations varying from 0.1 up to 5.1 microg kg(-1) dry wt. For the various sampling points the proportional mass flows deriving from wastewater discharges were calculated. Whereas only up to 10% of the average flow is discharged wastewater up to more than 50% of the PFAS mass flows in the rivers can be attributed to wastewater discharges. Besides wastewater different other pathways as emissions from point sources, further degradation of precursor products, runoff from contaminated sites or surface runoff as well as dry and wet deposition have to be considered as relevant sources for PFAS contamination in surface waters.

Abstract  Semivolatile fluorinated organic compounds (FOCs) were measured in archived air sample extracts collected from Hedo Station Observatory (HSO) on Okinawa, Japan and Mount Bachelor Observatory (MBO), Oregon U.S. during the springs of 2004 (MBO and HSO) and 2006 (MBO). Fluorotelomer alcohols (FTOHs) were measured in both Asian and western U.S. air masses, though western U.S. air masses had significantly higher concentrations. Concentrations of fluorotelomer olefins in Asian air masses and 8:2 fluorotelomer acrylate in U.S. air masses were reported for the first time. N-ethyl perfluorooctane sulfonamide, N-methyl perfluorooctane sulfonamido ethanol, and N-ethyl perfluorooctane sulfonamido ethanol were also measured in Asian and western U.S. air masses but less frequently than FTOHs. The atmospheric sources and fate of FTOHs were investigated by estimating their atmospheric residence times, calculating FTOH concentration ratios, investigating FTOH correlations with nonfluorinated semivolatile organic compound concentrations, and determining air mass back trajectories. Estimated atmospheric residence times for 6:2 FTOH, 8:2 FTOH, and 10:2 FTOH were 50, 80, and 70 d, respectively, and the average concentration ratio of 6:2 FTOH to 8:2 FTOH to 10:2 FTOH at MBO in 2006 was 1.0 to 5.0 to 2.5. The relative order of these atmospheric residence times may explain the observed enhancement of 8:2 FTOH and 10:2 FTOH (relative to 6:2 FTOH) at MBO compared to North American indoor air (FTOH average ratio of 1.0 to 2.0 to 1.0). FTOH concentrations in western U.S. air masses were positively correlated (p < 0.05) with gas-phase polycyclic aromatic hydrocarbon and polychlorinated biphenyl concentrations and negatively correlated (p < 0.05) with agricultural pesticide concentrations. In comparison to western U.S. air masses, trans-Pacific air masses did not contain elevated concentrations of these compounds, whereas lower boundary layer air masses that passed over urban areas of the western U.S. did. This suggests that semivolatile FOCs are emitted from urban areas in the western U.S.

Abstract  OBJECTIVE: The objective of this study was to determine serum (perfluorooctanoate [PFOA]) in residents near a fluoropolymer production facility: the contributions from air, water, and occupational exposures, personal and dietary habits, and relationships to age and gender.

METHODS: The authors conducted questionnaire and serum PFOA measurements in a stratified random sample and volunteers residing in locations with the same residential water supply but with higher and lower potential air PFOA exposure.

RESULTS: Serum (PFOA) greatly exceeded general population medians. Occupational exposure from production processes using PFOA and residential water had additive effects; no other occupations contributed. Serum (PFOA) depended on the source of residential drinking water, and not potential air exposure. For public water users, the best-fit model included age, tap water drinks per day, servings of home-grown fruit and vegetables, and carbon filter use.

CONCLUSIONS: Residential water source was the primary determinant of serum (PFOA).

Abstract  Perfluorochemicals (PFCs) are the subject of increasingly intense environmental research. Despite their detection both in biota and in aqueous systems, little attention has been paid to the possible presence of this class of compounds in solid environmental matrixes. The limited available data indicate that some PFCs such as perfluorooctane sulfonate (PFOS) may strongly sorb to solids, and sewage sludge is widely suspected as a major sink of PFCs entering municipal waste streams. A quantitative analytical method was developed that consists of liquid solvent extraction of the analytes from sediments and sludge, cleanup via solid-phase extraction, and injection of the extracts with internal standards into a high-performance liquid chromatography (HPLC) system coupled to a tandem mass spectrometer (LC/MS/MS). The limits of detections of the method were analyte and matrix dependent, but ranged from 0.7 to 2.2 ng/g and 0.041 to 0.246 ng/g (dry weight) for sludge and sediment, respectively. A demonstration of the method was performed by conducting a limited survey of domestic sludge and sediments. The concentration of PFCs in domestic sludge ranged from 5 to 152 ng/g for total perfluorocarboxylates and 55 to 3370 ng/g for total perfluoroalkyl sulfonyl-based chemicals. Data from a survey of San Francisco Bay Area sediments suggest widespread occurrence of PFCs in sediments at the low ng/g to sub-ng/g level. Furthermore, substances that may be transformed to PFOS, such as 2-(N-ethylperfluorooctanesulfonamido) acetic acid (N-EtFOSAA) and 2-(N-methylperfluorooctanesulfonamido) acetic acid (N-MeFOSAA), are present in both sediments and sludge at levels often exceeding PFOS.

Abstract  Perfluorooctanoic acid and perfluorooctane sulfonate were determined in the sediments from Winam Gulf, which is in the Kenyan side of Lake Victoria and in its source rivers. The sources of perfluorinated compounds within the Gulf of Lake Victoria have been identified and their levels determined for the first time, in this study, using SPE and HPLC-MS-MS analytical methodology. Variability in the concentrations of perfluorooctanoic acid and perfluorooctane sulfonate ranged from 1.4–99.1 and <1–57.5 ng/g in river sediments, respectively, which was higher than concentrations obtained from lake sediments (range perfluorooctanoic acid <1–24.1 ng/g and perfluorooctane sulfonate <1–4.0 ng/g). The results obtained suggested generalized point sources such as domestic and industrial waste indicated by significant correlation and regression of r2 = 0.857. Sampling sites within and near sewage and water treatment facilities gave the highest concentrations of both analytes, and were observed to be the main source of perfluorinated compounds pollution. The lowest limit of quantification was 1 ng/g for both analytes and limits of detection were 0.1 and 0.2 ng/g for perfluorooctanoic acid and perfluorooctane sulfonate, respectively. Typical values for recovery obtained were higher than 78% from spiked amounts ranging from 1 to 150 ng. Quantifying perfluoro alkylated compounds in sediments have provided insights into their source, distribution, and mobility in the Lake Victoria Basin.

Abstract  Perfluorooctanoic acid (PFOA) is an environmentally persistent chemical used in the manufacturing of a wide array of industrial and commercial products. PFOA has been shown to induce tumors of the liver, testis and pancreas (tumor triad) in rats following chronic dietary administration. PFOA belongs to a group of compounds that are known to activate the PPARα receptor. The PPARα activation Mode of Action was initially addressed in 2003 [9] and further refined in subsequent reviews [92-94]. In the intervening time, additional information on PFOA effects as well as a further refinement of the Mode of Action framework warrants a re-examination of this compound for its cancer induction Mode of Action. This review will address the rodent (rat) cancer data and cancer Mode of Action of PFOA for tumors of the liver, testes and pancreas.