2003 Abstracts

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Abstracts on PFOS and PFOA for the following years:

NOTE: The interest of the FAN Pesticide Project in this issue is directly related to the fact that several PFOS and PFOA chemicals were used as "inerts" in pesticides. However, most, but not all, have been deleted from use since 2001. The so-called "inerts" are used in pesticides and can account for as much as 99%, or more, of a pesticidal formulation. US EPA's policy is to allow the public information only on the "active substance" and to deny the public the names of the chemicals used as "inerts" in specific pesticide products -- even though the majority of inerts are toxic and biologically active.

• See the molecular structure for some of these chemicals

• The following is a selected list of abstracts. For more see PubMed or Toxnet.

Reports and statements from EPA:

April 10, 2003. Preliminary Risk Assessment on the Developmental Toxicity Associated with Exposure to Perfluorooctanoic Acid and its Salts

U.S.Environmental Protection Agency. Office of Pollution Prevention and Toxics Risk Assessment Division.

April 14, 2003. US EPA Fact Sheet on PFOA

U.S.Environmental Protection Agency. Office of Pollution Prevention and Toxics Risk Assessment Division.

April 14, 2003. EPA intensifies scientific investigation of a chemical processing aid

US EPA Environmental News

2003. US EPA Timeline on PFOA

March 31, 2003. Letter to US EPA from APFO-user Industries

1. APFO users: Asahi Glass Fluoropolymers USA, Inc., Daikin America, Inc., Dyneon, LLC, and E.I. du Pont de Nemours and Company. These companies use APFO as a polymerization aid to manufacture fluoropolymers and fluoroelastomers. DuPont also manufacturers APFO in the United States for use in fluoropolymer manufacturing.

2. Telomer Companies: AGA Chemicals, Inc., Clariant GmbH, Daikin America, Inc., and E.I. du Pont de Nemours and Company. These companies produce or import fluorotelomer-based products, which are used as fluorosurfactants and surface protection chemicals.

3. The 3M Company, the former U.S. manufacturer of APFO.

Environ Health Perspect. 2003 Sep;111(12):1485-9.

Neuroendocrine effects of perfluorooctane sulfonate in rats.

Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM.

Neuroendocrine Research Laboratory, Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine Center, Michigan State University, East Lansing, Michigan, USA.

Perfluorooctane sulfonate (PFOS) is a degradation product of sulfonyl-based fluorochemicals that are used extensively in industrial and household applications. Humans and wildlife are exposed to this class of compounds from several sources. Toxicity tests in rodents have raised concerns about potential developmental, reproductive, and systemic effects of PFOS. However, the effect of PFOS on the neuroendocrine system has not been investigated thus far. In this study, adult female rats were injected intraperitoneally with 0, 1, or 10 mg PFOS/kg body weight (BW) for 2 weeks. Food and water intake, BW, and estrous cycles were monitored daily. At the end of treatment, PFOS levels in tissues were measured by high-performance liquid chromatography (HPLC) interfaced with electrospray mass spectrometry. Changes in brain monoamines were measured by HPLC with electrochemical detection, and serum corticosterone and leptin were monitored using radioimmunoassay. Treatment with PFOS produced a dose-dependent accumulation of this chemical in various body tissues, including the brain. PFOS exposure decreased food intake and BW in a dose-dependent manner. Treatment with PFOS affected estrous cyclicity and increased serum corticosterone levels while decreasing serum leptin concentrations. PFOS treatment also increased norepinephrine concentrations in the paraventricular nucleus of the hypothalamus. These results indicate that exposure to PFOS can affect the neuroendocrine system in rats.

PMID: 12948888 [PubMed - in process]

Mother in Class Action speaks of the developmental problem suffered by her young daughter-

"... Debra Cochran of Pageville, a stay-home mother of three, has begun her own investigation into the substance, driven by fears about her family's health. News reports about C8 peaked her interest months ago and now she is trying to find out if the manufacturing chemical could be a contributing factor in a developmental problem suffered by her 6-year-old daughter, Lauren.

"We thought her teeth came in without enamel," Cochran said. Lauren had to have her teeth removed after they failed to develop properly. Recently Cochran has discovered that several other families in her area have experienced the same problem...

Ref: September 27, 2003
Examining the water we drink:Concerns about C8 linger
By Callie Lyons. The Marietta Times (Ohio).

Birth Defects Res Part B Dev Reprod Toxicol. 2003 Dec;68(6):465-71.
Prenatal window of susceptibility to perfluorooctane sulfonate-induced neonatal mortality in the Sprague-Dawley rat.

Grasty RC, Grey BE, Lau CS, Rogers JM.

Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

The critical period for increased neonatal mortality induced by perfluorooctane sulfonate (PFOS) exposure was evaluated in the rat. Timed-pregnant Sprague-Dawley rats were treated by oral gavage with 25 mg/kg/d PFOS/K(+) on four consecutive days (gestation days (GD) 2-5, 6-9, 10-13, 14-17, or 17-20) or with 0, 25, or 50 mg/kg/d PFOS/K(+) on GD 19-20. Controls received vehicle (10 ml/kg 0.5% Tween-20) on these days. Maternal weight gain was reduced in treated animals during dosing, as were food and water consumption. Following a 4-day treatment, litter size at birth was unaffected while pup weight was similarly reduced in the three earliest PFOS groups. All PFOS groups experienced decreases in survival while controls remained near 100%. Neonatal survival decreased in groups dosed later during gestation, approaching 100% with dosing on GD 17-20. Most deaths occurred before postnatal day (PND) 4, with the majority in the first 24 hours. Maternal serum PFOS levels on GD 21 were higher in groups exhibiting higher mortality. Following a 2-day treatment, PFOS groups experienced significant pup mortality by PND 1. Neonatal mortality continued through PND 5, when survival was 98, 66, and 3% for the 0, 25, and 50 mg/kg groups, respectively. Pup weight was reduced in treated groups with surviving litters. Gross dissection and histological examination of lungs revealed differences in maturation between control and treated animals on PND 0. We conclude that exposure to PFOS late in gestation is sufficient to induce 100% pup mortality and that inhibition of lung maturation may be involved.

PMID: 14745980 [PubMed - in process]

Environ Sci Technol. 2003 Dec 15;37(24):5545-50.

Perfluorinated chemicals infiltrate ocean waters: link between exposure levels and stable isotope ratios in marine mammals.

Van de Vijver KI, Hoff PT, Das K, Van Dongen W, Esmans EL, Jauniaux T, Bouquegneau JM, Blust R, de Coen W.

Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerpen, Belgium.

This is the first study to report on concentrations of perfluorinated organochemicals (FOCs) in marine mammals stranded along the southern North Sea coast in relation to stable nitrogen and carbon isotope ratios (delta15N and delta13C). The presence of FOCs in top predators such as marine mammals would indicate a potential biomagnification of these compounds and their widespread occurrence. Liver and kidney tissues of nine marine mammal species have been sampled. Among all the measured FOCs compounds, PFOS (perfluorooctane sulfonate) was predominant in terms of concentration. The highest PFOS concentrations were found in the liver of harbor seal compared to white-beaked dolphin, harbor porpoise, gray seal, sperm whale, white-sided dolphin, striped dolphin, fin whale, and hooded seal. PFOS concentrations differed significantly between sexes and age classes in harbor porpoises. Stable isotope measurements (delta13C and delta15N) were used in this study to describe the behavior of contaminants in food webs. We found a significant (p < 0.05) linear relationship between PFOS concentrations in livers of harbor porpoises and both muscle delta13C and delta15N measurements. Harbor and gray seals and white-beaked dolphin, which displayed the highest trophic position, contained the highest PFOS levels, while offshore feeders such as sperm whales, fin whales, striped dolphin, and white-sided dolphin showed lower PFOS concentrations than inshore species.

PMID: 14717162 [PubMed - in process]

Environ Toxicol Chem. 2003 Nov;22(11):2639-49.

Binding of perfluorinated fatty acids to serum proteins.

Jones PD, Hu W, De Coen W, Newsted JL, Giesy JP.

Department of Zoology, National Food Safety and Toxicology Center, Institute for Environmental Toxicology, Michigan State University, East Lansing, Michigan 48824, USA.

Perfluorooctane sulfonic acid (PFOS) accumulates in the liver and blood of exposed organisms. The potential for these surfactant molecules to interfere with hormone/protein interactions in blood is of concern given the importance of these interactions. The PFOS binding to serum proteins was investigated by assessing its ability to displace a variety of steroid hormones from specific binding proteins in the serum of birds and fishes. Perfluorooctane sulfonic acid had only a weak ability to displace estrogen or testosterone from carp serum steroid binding proteins. Displacement of cortisone in avian sera occurred at relatively low PFOS concentrations. Corticosterone displacement potency increased with chain length, and sulfonic acids were more potent than carboxylic acids. The PFOS concentrations estimated to cause these effects were 320 microM or greater, equivalent to serum concentrations greater than 160 mg/L. Using mass spectrometry and direct in vitro binding assays, PFOS was demonstrated to bind strongly to bovine serum albumin (BSA) in a 1:1 stoichiometric ratio. It appears that PFOS in serum is in general bound to albumins. Concentrations of PFOS required to saturate albumin would be in excess of 50 to 100 mg/L. Based on current environmental concentrations, it is unlikely that PFOS would cause displacement of hormones from serum proteins in wildlife.

PMID: 14587903 [PubMed - in process]

Environ Health Perspect. 2003 Dec;111(16):1892-901.
Perfluorooctanesulfonate and other fluorochemicals in the serum of american red cross adult blood donors.

Olsen GW, Church TR, Miller JP, Burris JM, Hansen KJ, Lundberg JK, Armitage JB, Herron RM, Medhdizadehkashi Z, Nobiletti JB, O'Neill EM, Mandel JH, Zobel LR.

Medical Department, 3M Company, St. Paul, Minnesota 55144, USA.

Perfluorooctanesulfonyl fluoride-based products have included surfactants, paper and packaging treatments, and surface protectants (e.g., for carpet, upholstery, textile). Depending on the specific functional derivatization or degree of polymerization, such products may degrade or metabolize, to an undetermined degree, to perfluorooctanesulfonate (PFOS), a stable and persistent end product that has the potential to bioaccumulate. In this investigation, a total of 645 adult donor serum samples from six American Red Cross blood collection centers were analyzed for PFOS and six other fluorochemicals using HPLC-electrospray tandem mass spectrometry. PFOS concentrations ranged from the lower limit of quantitation of 4.1 ppb to 1656.0 ppb with a geometric mean of 34.9 ppb [95% confidence interval (CI), 33.3-36.5]. The geometric mean was higher among males (37.8 ppb; 95% CI, 35.5-40.3) than among females (31.3 ppb; 95% CI, 30.0-34.3). No substantial difference was observed with age. The estimate of the 95% tolerance limit of PFOS was 88.5 ppb (upper limit of 95% CI, 100.0 ppb). The measures of central tendency for the other fluorochemicals (N-ethyl perfluorooctanesulfonamidoacetate, N-methyl perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamide, perfluorooctanoate, and perfluorohexanesulfonate) were approximately an order of magnitude lower than PFOS. Because serum PFOS concentrations correlate with cumulative human exposure, this information can be useful for risk characterization.

PMID: 14644663 [PubMed - in process]

J Chromatogr A. 2003 Dec 5;1020(1):131-51.

Determination of fluorinated surfactants and their metabolites in sewage sludge samples by liquid chromatography with mass spectrometry and tandem mass spectrometry after pressurised liquid extraction and separation on fluorine-modified reversed-phase sorbents.

Schroder HF.

Institut fur Siedlungswasserwirtschaft, Aachen University, Templergraben 55, D-52056 Aachen, Germany.

An analytical method was elaborated for simultaneous extraction and determination of fluorinated anionic and non-ionic surfactants in sewage sludge. Surfactant compounds were determined by liquid chromatography-mass spectrometry (LC-MS) after Soxhlet extraction, hot steam extraction and pressurised liquid extraction (PLE) using spiked sludge samples. PLE in a multiple-step procedure consisting of sequential use of ethyl acetate-dimethylformamide and methanol-phosphoric acid resulted in the most efficient extraction procedure. Quantitative analyses of the fluorinated anionic perfluorooctanesulfonate (PFOS) and the partly fluorinated non-ionic alkylpolyglycol ether (FAEO) surfactants were performed by selected ion monitoring LC-MS. Electrospray ionisation or atmospheric pressure chemical ionisation in negative or positive mode was performed. Recoveries between 105 and 120% could be reached. No PFOS and non-ionic FAEO surfactants in concentrations higher than 6 or 10 mg kg(-1) dry matter were observed in real environmental samples. Therefore aerobic and anaerobic biodegradation was performed to investigate the fate of fluorinated surfactants reaching wastewaters. Biological wastewater treatment in laboratory scale under aerobic or anaerobic conditions led to an elimination by biodegradation.

PMID: 14661764 [PubMed - in process]

Occup Environ Med. 2003 Oct;60(10):722-9.

Mortality of employees of a perfluorooctanesulphonyl fluoride manufacturing facility.

Alexander BH, Olsen GW, Burris JM, Mandel JH, Mandel JS.

University of Minnesota, School of Public Health, Division of Environmental and Occupational Health, MMC 807 Mayo Building, 420 Delaware St, SE Minneapolis, MN 55409, USA. AIM:

To evaluate the mortality experience of a cohort of employees of a perfluorooctanesulphonyl fluoride (POSF) based fluorochemical production facility.
METHODS: A retrospective cohort mortality study followed all workers with at least one year of cumulative employment at the facility. The jobs held by cohort members were assigned to one of three exposure subgroups; high exposed, low exposed, and non-exposed, based on biological monitoring data for perfluorooctane sulphonate (PFOS).
RESULTS: A total of 145 deaths were identified in the 2083 cohort members. Sixty five deaths occurred among workers ever employed in high exposed jobs. The overall mortality rates for the cohort and the exposure subcohorts were lower than expected in the general population. Two deaths from liver cancer were observed in the workers with at least one year of high or low exposure (standardised mortality ratio (SMR) 3.08, 95% CI 0.37 to 11.10). The risk of death from bladder cancer was increased for the entire cohort (three observed, SMR 4.81, 95% CI 0.99 to 14.06). All three bladder cancers occurred among workers who held a high exposure job (SMR 12.77, 95% CI 2.63 to 37.35). The bladder cancer cases primarily worked in non-production jobs, including maintenance and incinerator and wastewater treatment plant operations.
CONCLUSION: Workers employed in high exposure jobs had an increased number of deaths from bladder cancer; however it is not clear whether these three cases can be attributed to fluorochemical exposure, an unknown bladder carcinogen encountered during the course of maintenance work, and/or non-occupational exposures. With only three observed cases the possibility of a chance finding cannot be ruled out.

PMID: 14504359 [PubMed - indexed for MEDLINE]

J Environ Monit. 2003 Oct;5(5):753-7.

Concentrations of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) in vacuum cleaner dust collected in Japanese homes.

Moriwaki H, Takatah Y, Arakawa R.

Osaka City Institute of Public Health & Environmental Sciences, 8-34 Tojo-cho, Tennoji-ku, Osaka 543-0026, Japan.

Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are shown to be globally distributed, environmentally persistent and bioaccumulative. Although there is evidence that these compounds exist in the serum of non-occupationally exposed humans, the pathways leading to the presence of PFOS and PFOA are not well characterized. The concentrations of PFOS and PFOA in the vacuum cleaner dust collected in Japanese homes were measured. The compounds were detected in all the dust samples and the ranges were 11-2500 ng g(-1) for PFOS and 69-3700 ng g(-1) for PFOA. It was ascertained that PFOS and PFOA were present in the dust in homes, and that the absorption of the dust could be one of the exposure pathways of the PFOS and PFOA to humans. With regard to risk management, it is important to consider the usage of PFOS and PFOA in the indoor environment in order to avoid further pollution.

PMID: 14587845 [PubMed - in process]

Arch Environ Contam Toxicol. 2003 Aug;45(2):149-58.

Perfluorooctane sulfonate concentrations in surface water in Japan.

Saito N, Sasaki K, Nakatome K, Harada K, Yoshinaga T, Koizumi A.

Research Institute for Environmental Sciences and Public Health of Iwate Prefecture, Morioka Iwate, Japan.

Perfluorooctane sulfonate (PFOS) is a class of specialty chemicals used in a variety of applications, and has been found to be globally distributed in many living organisms including humans. Several analytical methods have been developed for determination of PFOS in environmental samples and biological matrices. However, these methods employ liquid chromatography/tandem mass spectrometry (LC/MS/MS), an instrumentation which has limited accessibility because it is expensive to use and maintain. In the present study we present the development of a robust analytical method using liquid chromatography/mass spectrometry (LC/MS) in combination with solid phase extraction. The high yield and concentration of the present method enabled us to quantify PFOS as low as 0.1 ng/L. This method was applied to the determination of PFOS in 142 surface water samples collected from various geographic locations around Japan. The geometric mean (geometric standard deviation) (ng/L) for river samples (n = 126) was 2.37 (4.13), with a median of 1.68 and a range of 0.3-157 ng/L, and for coastal sea water samples (n = 16) was 1.52 (4.14), with a median of 1.21 and a range of 0.2-25.2 ng/L. However, the concentrations in most of the samples were much lower than the values reported in the US, except for those from the Jinzu (135.0 ng/L) and Tama (157 ng/L) Rivers. Because surface waters in the Ara (13.0-38.5 ng/L), Tama (0.7-157.0 ng/L), and Yodo (0.9-27.3 ng/L) Rivers, sources of drinking water for more than eight million people, were moderately contaminated with PFOS, more work is needed to assess exposure to PFOS.

PMID: 14565571 [PubMed - in process]

AIHA J (Fairfax, Va). 2003 Sep-Oct;64(5):651-9.

An occupational exposure assessment of a perfluorooctanesulfonyl fluoride production site: biomonitoring.

Olsen GW, Logan PW, Hansen KJ, Simpson CA, Burris JM, Burlew MM, Vorarath PP, Venkateswarlu P, Schumpert JC, Mandel JH.

Medical Department, 3M Co., St. Paul, MN 55144, USA.

This investigation randomly sampled a fluorochemical manufacturing employee population to determine the distribution of serum fluorochemical levels according to employees' jobs and work areas. Previous analyses of medical surveillance data have not shown significant associations between fluorochemical production employees' clinical chemistry and hematology tests and their serum PFOS and perfluorooctanoate (PFOA, C(7)F(15)COO(-)) concentrations, but may have been subject to nonparticipation bias. A random sample of the on-site film plant employee population, where fluorochemicals are not produced, determined their serum concentrations also. Of the 232 employees randomly selected for serum sampling, 186 (80%) employees participated (n=126 chemical plant; n=60 film plant). Sera samples were extracted using an ion-pairing extraction procedure and were quantitatively analyzed for seven fluorochemicals using high-pressure liquid chromatography electrospray tandem mass spectrometry methods. Geometric means (in parts per million) and 95% confidence intervals (in parentheses) of the random sample of 126 chemical plant employees were: PFOS 0.941 (0.787-1.126); PFOA 0.899 (0.722-1.120); perfluorohexanesulfonate 0.180 (0.145-0.223); N-ethyl perfluorooctanesulfonamidoacetate 0.008 (0.006-0.011); N-methyl perfluorooctanesulfonamidoacetate 0.081 (0.067-0.098); perfluorooctanesulfonamide 0.013 (0.009-0.018); and perfluorooctanesulfonamidoacetate 0.022 (0.018-0.029). These geometric means were approximately one order of magnitude higher than those observed for the film plant employees.

PMID: 14521435 [PubMed - in process]

Environ Toxicol Chem. 2003 Nov;22(11):2739-45.

Response of the zooplankton community and environmental fate of perfluorooctane sulfonic acid in aquatic microcosms.

Boudreau TM, Wilson CJ, Cheong WJ, Sibley PK, Mabury SA, Muir DC, Solomon KR.

Centre for Toxicology, Department of Environmental Biology, Bovey Building, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

Little is known regarding perfluorooctane sulfonic acid (PFOS) toxicity to freshwater organisms. This field evaluation aims to assess the toxicological risk associated with exposure to PFOS across levels of biological organization. The analysis of variance study was conducted in replicate (n = 3) 12,000 L outdoor microcosms. Multivariate techniques were used to assess the response of zooplankton community structure and dynamics, as well as a floating macrophyte, Lemna gibba. The zooplankton community was significantly affected (p < 0.05) by the treatment regime given by the Monte Carlo permutations for all sampling times. A community-level no-observable-effect concentration ([NOEC]community) of 3.0 mg/L was determined for the 35-day study, however, longer term studies are recommended. The most sensitive taxonomic groups, Cladocera and Copepoda, were virtually eliminated in 30 mg/L treatments after 7 d. The 42-d 50% inhibition concentration (IC50) for L. gibba frond number was 19.1 mg/L and the NOEC was 0.2 mg/L. Furthermore, we investigated the persistence of PFOS over 285 d in microcosms under natural conditions. Perfluorooctane sulfonic acid concentration showed no drastic reduction in any treatment microcosm over the entire study period, confirming that this compound undergoes little degradation in aquatic systems. Presently, there appears to be little hazard to these freshwater organisms at reported environmental concentrations.

PMID: 14587916 [PubMed - in process]

Environ Toxicol Chem. 2003 Sep;22(9):2037-41.

Exposure patterns of perfluorooctane sulfonate in aquatic invertebrates from the Western Scheldt estuary and the southern North Sea.

Van de Vijver KI, Hoff PT, Van Dongen W, Esmans EL, Blust R, De Coen WM.

Over the past decades little research has been conducted on the environmental behavior and effects of fluorinated organochemicals (FOCs). Recently it has been reported that perfluorooctane sulfonic acid (PFOS) is occurring worldwide. Little is known about the PFOS levels in organisms originating from the southern North Sea and the Western Scheldt estuary. In this study, we determined, for the first time, the PFOS-exposure levels in Crangon crangon, Carcinus maenas, and Asterias rubens from these ecosystems. Concentrations on a wet-weight basis in soft tissues of shrimp, crab, and starfish ranged from 19 to 520 ng/g, from 24 to 877 ng/g, and from 9 to 176 ng/g, respectively. These results show the existence of a PFOS pollution gradient in organisms along the Western Scheldt estuary, with the highest concentrations near Antwerp. The range of PFOS levels in shrimp and crab are slightly higher in coastal regions compared with sampling sites in open water. This study shows widespread distribution of PFOS in the Belgian and Dutch marine and estuarine environment at rather high concentrations.

PMID: 12959528 [PubMed - in process]

Biochem Pharmacol. 2003 Sep 1;66(5):749-56.

The relationship between liver peroxisome proliferation and adipose tissue atrophy induced by peroxisome proliferator exposure and withdrawal in mice.

Xie Y, Yang Q, Nelson BD, DePierre JW.

Unit for Biochemical Toxicology, Wallenberg Laboratory, Department of Biochemistry and Biophysics, Stockholm University, S-106 91, Stockholm, Sweden

We have previously demonstrated that severe adipose tissue atrophy occurs upon dietary treatment of mice with potent peroxisome proliferators (PPs). This atrophy occurs subsequent to peroxisome proliferation in the liver and may represent a novel addition to the pleiotropic effects exerted by PPs. In the present study we have characterized the recovery of mice from such atrophy following cessation of exposure. Following termination of treatment with perfluorooctanoic acid (PFOA) for 7 days, the adipose tissue atrophy was rapidly reversed, beginning on 2-5 days of recovery and being complete within 10 days. In contrast, hepatic peroxisome proliferation recovered much more slowly, indicating that these processes are not strictly coordinated. Analysis of lipoprotein lipase and hormone-sensitive lipase activities in adipose tissue revealed that the decrease and increase in these activities, respectively, caused by PFOA were both reversed within 10 days of recovery. Overall, these data provide further support for our previous conclusion that the adipose tissue atrophy induced by PFOA is caused, at least in part, by changes in the activities of lipoprotein lipase and hormone-sensitive lipase. The serum level of cholesterol, which increased after termination of PFOA treatment, returned to normal with a time-course similar to the recovery of adipose tissue weight, although hepatic peroxisome proliferation was still present. The possible relationship between the reduction in serum cholesterol and/or in its availability to peripheral tissues and the associated atrophy of adipose tissues caused by PPs is discussed.

PMID: 12948855 [PubMed - in process]

Environ Sci Technol. 2003 Jun 15;37(12):2634-9.

A survey of perfluorooctane sulfonate and related perfluorinated organic compounds in water, fish, birds, and humans from Japan.

Taniyasu S, Kannan K, Horii Y, Hanari N, Yamashita N.

National Institute of Advanced Industrial Science and Technology (AIST), 16-1 Onogawa, Tsukuba, Ibaraki 305-8569, Japan.

Occurrence of perfluorooctane sulfonate (PFOS) in the tissues of humans and wildlife is well documented. In this study, concentrations and distribution of PFOS, perfluorohexane sulfonate (PFHS), and perfluorobutane sulfonate (PFBS) were determined in samples of surface water, fish and bird blood and livers, and human blood collected in Japan. Notable concentrations of PFOS were found in surface water and fish from Tokyo Bay. PFOS was found in all of the 78 samples of fish blood and liver analyzed. Based on the concentrations of PFOS in water and in fish livers, bioconcentration factors were calculated to range from 274 to 41 600. Concentrations of PFOS in the blood of Japanese human volunteers ranged from 2.4 to 14 ng/mL. PFHS was detected in 33% of the fishes analyzed, at concentrations severalfold less than those of PFOS.

PMID: 12854699 [PubMed - in process]

J Toxicol Sci. 2003 May;28(2):49-57. R

Toxicity and toxicokinetics of perfluorooctanoic acid in humans and animals.

Kudo N, Kawashima Y.

Department of Toxicology and Applied Pharmacology, Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama 350-0295, Japan.

Perfluorooctanoic acid (PFOA) is an octanoic acid derivative to which all aliphatic hydrocarbons are substituted by fluorine. PFOA and its salts are commercially used in various industrial processes. The chemical is persistent in the environment and does not undergo biotransformation. It was reported that PFOA is found not only in the serum of occupationally exposed workers but also general populations. Recent studies have suggested that the biological half-life of PFOA in humans is 4.37 years based on study of occupationally exposed workers. It is increasingly suspect that PFOA accumulates and affects human health, although the toxicokinetics of PFOA in humans remain unclear. In experimental animals, PFOA seems low in toxicity. PFOA is well-absorbed following oral and inhalation exposure, and to a lesser extent following dermal exposure. Once absorbed in the body, it distributes predominantly to the liver and plasma, and to a lesser extent the kidney and lungs. PFOA is excreted in both urine and feces. Biological half-life of PFOA is quite different between species and sexes and the difference is due mainly to the difference in renal clearance. In rats, renal clearance of PFOA is regulated by sex hormones, especially testosterone. PFOA is excreted into urine by active tubular secretion, and certain organic anion transporters are though to be responsible for the secretion. Fecal excretion is also important in the elimination of PFOA. There is evidence that PFOA undergoes enterohepatic circulation resulting in reduced amounts of fecal excretion. Elucidation of the mechanisms of transport in biological systems leads to elimination and detoxification of this chemical in the human body.

PMID: 12820537 [PubMed - in process]

Chem Res Toxicol. 2003 Jun;16(6):775-81.

Binding of perfluorooctanoic Acid to rat and human plasma proteins.

Han X, Snow TA, Kemper RA, Jepson GW.

DuPont Haskell Laboratory for Health and Environmental Sciences, P.O. Box 50, Newark, Delaware 19714.

Perfluorooctanoic acid (PFOA) is a commercially important organic fluorochemical and is considered to have a long half-life in human blood. In this paper, PFOA binding to rat and human plasma proteins was investigated. On the basis of results from size-exclusion chromatography and ligand blotting, most PFOA was in protein-bound form in male and female rat plasma, and the primary PFOA binding protein in plasma was serum albumin. PFOA binding to rat serum albumin (RSA) in the gas phase was observed by electrospray ionization MS. (19)F NMR experiments revealed that binding to RSA caused peak broadening and chemical shift changes of PFOA resonances, and on the basis of this observation, the dissociation constant was determined to be approximately 0.3 mM. The dissociation constants for PFOA binding to RSA and human serum albumin (HSA) and the numbers of PFOA binding sites on RSA and HSA were also determined by a separation method using microdesalting columns. No significant difference was found between PFOA binding to RSA and PFOA binding to HSA. The dissociation constants for binding of PFOA to RSA or HSA and the numbers of PFOA binding sites were in the range of 0.3-0.4 mM and 6-9, respectively. On the basis of these binding parameters and the estimated plasma concentration of serum albumin, greater than 90% of PFOA would be bound to serum albumin in both rat and human blood.

PMID: 12807361 [PubMed - in process]

Comp Biochem Physiol C Toxicol Pharmacol. 2003 May;135(1):77-88.

Alterations in cell membrane properties caused by perfluorinated compounds.

Hu W, Jones PD, DeCoen W, King L, Fraker P, Newsted J, Giesy JP.

National Food Safety and Toxicology Center, Institute for Environmental Toxicology and Department of Zoology, Michigan State University, MI 48824, East Lansing, USA

The recent detection of perfluorinated compounds (PFCs) in wildlife from even remote locations has spurred interest in the environmental occurrence and effects of these chemicals. While the global distribution of PFCs is increasingly understood, there is still little information available on their effects on wildlife. The amphiphillic nature of PFCs suggests that their effects could be primarily on cell membranes. In this study we measured the effects of PFCs on membrane fluidity and mitochondrial membrane potential using flow cytometry and effects on membrane permeability using cell bioassay procedures (H4IIE, MCF-7, PLHC-1). Of the PFCs tested, only perfluorooctane sulfonic acid (PFOS) increased the permeability of cell membranes to the hydrophobic ligands used. Three PFCs were tested in the membrane fluidity assay: PFOS, perfluorohexane sulfonic acid (PFHS), and perfluorobutane sulfonic acid (PFBS). PFOS increased membrane fluidity in fish leukocytes in a dose-dependent fashion, while PFHS and PFBS had no effect in the concentration range tested. The lowest effective concentrations for the membrane fluidity effects of PFOS were 5-15 mg/l. Effects on mitochondrial membrane potential occurred in the same concentration range as effects on membrane fluidity. This suggests that PFOS effects membrane properties at concentrations below those associated with other adverse effects.

PMID: 12781843 [PubMed - in process]

Toxicol Sci 2003 May 28; [epub ahead of print]

Exposure to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse.
Maternal and Prenatal Evaluations.

Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Barbee BD, Richards JH, Butenhoff JL, Stevenson LA, Lau C.

Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC.

The maternal and developmental toxicities of perfluorooctane sulfonate (PFOS) were evaluated in the rat and mouse. PFOS is an environmentally persistent compound used as a surfactant and occurs as a degradation product of both perfluorooctane sulfonyl fluoride and substituted perfluorooctane sulfonamido components found in many commercial and consumer applications. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestational day (GD) 2 to GD 20; CD-1 mice were similarly treated with 1, 5, 10, 15 and 20 mg/kg PFOS from GD 1 to GD 17. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). Maternal weight gain, food and water consumption, and serum chemistry were monitored. Rats were killed on GD 21, and mice on GD 18. PFOS levels in maternal serum, maternal and fetal livers were determined. Maternal weight gains in both species were suppressed by PFOS in a dose-dependent manner, likely attributed to reduced food and water intake. Serum PFOS levels increased with dosage, and liver levels were approximately 4-fold higher than serum. Serum thyroxine (T4) and triiodothyronine (T3) in the PFOS-treated rat dams were significantly reduced as early as one week after chemical exposure, although no feedback response of thyroid-stimulating hormone (TSH) was observed. A similar pattern of reduction in T4 was also seen in the pregnant mice. Maternal serum triglycerides were significantly reduced, particularly in the high dose groups, although cholesterol levels were not affected. In the mouse dams, PFOS produced a marked enlargement of the liver at 10 mg/kg and higher dosages. In the rat fetuses, PFOS was detected in the liver, but at levels nearly half of those in the maternal counterparts, regardless of administered doses. In both rodent species, PFOS did not alter the numbers of implantations or live fetuses at term, although small deficits in fetal weight were noted in the rat. A host of birth defects including cleft palate, anasarca, ventricular septal defect, and enlargement of the right atrium were seen in both rats and mice, primarily in the 10 and 20 mg/kg dosage groups, respectively. Our results demonstrate both maternal and developmental toxicity of PFOS in the rat and mouse.

PMID: 12773773 [PubMed - as supplied by publisher]

Toxicol Sci 2003 May 28; [epub ahead of print]

Exposure to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse.
II. Postnatal Evaluation.

Lau C, Thibodeaux JR, Hanson RG, Rogers JM, Grey BE, Stanton ME, Butenhoff JL, Stevenson LA.

Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC.

The postnatal effects of in utero exposure to perfluorooctane sulfonate (PFOS) were evaluated in the rat and mouse. Pregnant Sprague-Dawley rats were given 1, 2, 3, 5, or 10 mg/kg PFOS daily by gavage from gestation day (GD) 2 to GD 21; pregnant CD-1 mice were treated with 1, 5, 10, 15 and 20 mg/kg PFOS from GD 1 to GD 18. Controls received 0.5% Tween-20 vehicle (1 ml/kg for rats and 10 ml/kg for mice). At parturition, newborns were observed for clinical signs and survival. All animals were born alive and initially appeared to be active. In the highest dosage groups (10 mg/kg for rat and 20 mg/kg for mouse), the neonates became pale, inactive and moribund within 30-60 min, and all died soon afterward. In the 5 mg/kg (rat) and 15 mg/kg (mouse) dose groups, the neonates also became moribund but survived for a longer period of time (8-12 h). Over 95% of these animals died within 24 hr. Approximately 50% of offspring died at 3 mg/kg for rat and 10 mg/kg for mouse. Cross-fostering the PFOS-exposed rat neonates (5 mg/kg) to control nursing dams failed to improve survival. Serum concentrations of PFOS in newborn rats mirrored the maternal administered dosage and were similar to those in the maternal circulation at GD 21; PFOS levels in the surviving neonates declined in the ensuing days. Small but significant and persistent growth lags were detected in surviving rat and mouse pups exposed to PFOS prenatally, and slight delays in eye-opening were noted. Significant increases in liver weight were observed in the PFOS-exposed mouse pups. Serum thyroxine levels were suppressed in the PFOS-treated rat pups, although triiodothyronine and TSH levels were not altered. Choline acetyltransferase activity (an enzyme that is sensitive to thyroid status) in the prefrontal cortex of rat pups exposed to PFOS prenatally was slightly reduced, but activity in the hippocampus was not affected. Development of learning, determined by T-maze delayed alternation in weanling rats, was not affected by PFOS exposure. These results indicate that in utero exposure to PFOS severely compromised postnatal survival of neonatal rats and mice, and caused delays in growth and development that were accompanied by hypothyroxinemia in the surviving rat pups.

PMID: 12773772 [PubMed - as supplied by publisher]


Toxicologist 2003 Mar;72(S-1):342

Maternal and developmental toxicity of perfluorooctane sulfonate (PFOS) in the mouse.

Thibodeaux J Hanson RG Grey BE Barbee BD Richards JH Butenhoff JL Rogers JM Lau C

RTD, USEPA, Research Triangle Park, NC.

Abstract: The maternal and developmental toxicity of PFOS, an environmentally persistent compound that has been used in the manufacture of surfactants and insecticides, were evaluated. Timed-pregnant CD1 mice were gavaged with 1, 5, 10, 15, or 20 mg/kg/day PFOS/K+ from GD 2 to term. Controls received an equivalent volume of 0.5% Tween-20 vehicle (10 mL/kg). Some dams were killed on GD 18 for teratological examination, while those remaining were allowed to deliver to monitor the postnatal growth and development of their offspring. PFOS levels in maternal serum and liver were determined at term. Maternal weight gain was suppressed by 20 mg/kg PFOS, indicating the general maternal toxicity of the chemical. Serum triglycerides and thyroxine in dams treated with greater than 5 mg/kg PFOS were significantly lower than controls. Dose-dependent maternal liver weight increases were observed at term. PFOS did not alter the number of implantations, live fetuses, or fetal weight at term. Cleft palate, sternal defects, cardiac ventricular septal defect, and enlargement of the right atrium were detected, primarily in the 20 mg/kg group. Live birth was observed in all groups; however, neonates in the 20 mg/kg group were moribund and died within 4-6 h. While newborns in the 15 mg/kg group appeared viable, all were found dead within 24 h. Postnatal viability was greater in the lower dose groups and surviving neonates appeared to thrive, but significant delays in eye opening were observed. These dose-dependent adverse effects will be compared to the body burdens of PFOS. These results are similar to the maternal and developmental toxicity of PFOS previously described in the rat, although the mouse appears to be a less sensitive species.

International Standard Serial Number: 0731-9193

Publication Types: MEETING ABSTRACT

J Environ Monit 2003 Apr;5(2):341-5

Occurrence and persistence of perfluorooctanesulfonate and other perfluorinated surfactants in groundwater at a fire-training area at Wurtsmith Air Force Base, Michigan, USA.

Moody CA, Hebert GN, Strauss SH, Field JA.

Department of Chemistry, Oregon State University, Corvallis, Oregon 97331, USA.

Various formulations of fire-extinguishing materials, including aqueous film-forming foams (AFFFs), were used as part of fire-training exercises conducted at Wurtsmith Air Force Base (WAFB) in northeastern Michigan from the 1950s until the base was decommissioned in 1993. As a result of past fire-training exercises, AFFF-laden wastewater containing fuels, solvents, and other materials directly entered groundwater without prior treatment. Perfluorinated surfactants are key components in some AFFF formulations. In this study, groundwater was analyzed for perfluoroalkanesulfonates and perfluorocarboxylates. Perfluoroalkanesulfonates were directly detected using negative-ion electrospray ionization mass spectrometry. Derivatized perfluorocarboxylates were detected using electron impact gas chromatography-mass spectrometry. Groundwater from wells around fire-training area FTA-02 at WAFB contained four perfluorinated surfactants ranging in concentration from 3 to 120 microg L(-1): perfluorooctanesulfonate (PFOS); perfluorohexanesulfonate; perfluorooctanoate; and perfluorohexanoate. This is the first report demonstrating that PFOS, recently shown to be toxic to organisms ranging from zooplankton to primates, is still present in groundwater in measurable quantities five or more years after its last known use.

PMID: 12729279 [PubMed - in process]


Toxicologist 2003 Mar;72(S-1):76

Multi-generation reproduction study of ammonium perfluorooctanoate in rats.

Butenhoff JL, Kennedy GL, O'Connor JC, York RG

3M, Saint Paul, MN.

Ammonium perfluorooctanoate (APFO) is a surfactant used primarily as an aid in processing various fluoropolymers, and perfluorooctanoate has been identified in human sera from the US at very low concentrations (mean 6 ppb). The potential reproductive toxicity of APFO was studied using current EPA OPPTS 870.3800 guidelines. Male and female Sprague-Dawley rats were dosed orally with 0, 1, 3, 10, or 30 mg/kg/day APFO. P rats (approximately 6 weeks old) were dosed at least 70 days prior to mating and until sacrificed (after mating for males; after weaning for females). F1 rats were dosed similarly, beginning at weaning. The F2 pups were maintained through 22 days of lactation. Reproductive parameters evaluated in P and F1 rats included estrous cycling, sperm number and quality, mating, fertility, natural delivery, and litter viability and growth. Day of sexual maturation (F1) and anogenital distance (F2) were also determined. Feed consumption, body weight gain, selected organ weight, gross pathology and appropriate histopathology were collected. No effects on mating or fertility were discovered. P and F1 males experienced significant toxicity (decreased body weight and organ weight changes) even at the lowest dose tested, P females had reduced body weights and organ weight changes at 30 mg/kg/day, and F1 females had reduced body weight gains at 30 mg/kg/day and reduced pituitary weights at 3 mg/kg/day and higher. The 30 mg/kg/day F1 pups had decreased birth weight and viability; however, F2 pups at 30 mg/kg/day did not show a loss in viability. Sexual maturation was delayed in F1 (both sexes). Estrous periods per 21 days were increased in F1 females; however, this is likely an artifact of the evaluation method, as an evaluation of raw estrous cycling data did not indicate significant abnormalities. At the doses tested. APFO did not cause specific effects on reproductive capacity, but did produce toxicity and delayed sexual maturation. The NOAEL for reproduction was greater than 30 mg/kg (P and F1) based on lack of effect on mating, fertility, and natural delivery.

Aquat Toxicol. 2003 Feb 12;62(3):227-34.

Impact of perfluorooctanoic acid on the structure of the zooplankton community in indoor microcosms.

Sanderson H, Boudreau TM, Mabury SA, Solomon KR.

Department of Environment, Technology & Social Studies, University of Roskilde, PO-Box 260, DK 4000 Roskilde, Denmark.

There is presently, a substantial amount of information being gathered concerning the environmental risk associated with the perfluorooctanoic acid (PFOA) compound. The aim of this paper was to determine a 35 day community no observable effect concentration (NOEC(community)) or lowest observable effect concentration (LOEC) for freshwater zooplankton exposed to PFOA during a study in 30 l indoor aquatic microcosms. Some significant (P < 0.01) temporal fluctuations in zooplankton abundance were observed, however, a NOEC(community) could not be calculated. LOEC for various species varied between 10 and 70 mg l(-1). According to LOEC values, the tentative order of descriptors sensitivity was as follows: Daphnia magna > richness > or = Cyclops canthocamptus staphylinus > Cyclops diaptomus>total zooplankton > or = Rotifera sp. The long term ecological significance of these temporal fluctuations could not be determined in this study, however, the overall study cessation analysis showed that the structure of the ecosystem was changed from a more diverse community dominated by larger species towards a less diverse community dominated by smaller more and robust species (P < 0.05). Additional chronic toxicity testing should also be addressed since these compounds are so persistent and recalcitrant.

PMID: 12560171 [PubMed - indexed for MEDLINE]

Arch Environ Contam Toxicol 2003 Apr;44(3):307-13

Laboratory evaluation of the toxicity of Perfluorooctane Sulfonate (PFOS) on Selenastrum capricornutum, Chlorella vulgaris, Lemna gibba, Daphnia magna, and Daphnia pulicaria.

Boudreau TM, Sibley PK, Mabury SA, Muir DG, Solomon KR.

Centre for Toxicology, Department of Environmental Biology, Bovey Building, University of Guelph, Guelph, Ontario, N1G 2W1 Canada.

Perfluorooctane sulfonate (PFOS) is an anthropogenic compound found in trace amounts in many environmental compartments far from areas of production. This, along with the highly persistent nature of PFOS, presents a concern for possible effects in aquatic ecosystems. The objective of this study was to determine the toxicity of PFOS in representative freshwater organisms. Toxicity testing using standard laboratory protocols was performed on the green algae Selenastrum capricornutum and Chlorella vulgaris, the floating macrophyte Lemna gibba, and the invertebrates Daphnia magna and Daphnia pulicaria. No observable effect concentration (NOEC) values were generated from the most sensitive endpoints for all organisms. Autotroph inhibition of growth NOEC values were 5.3, 8.2, and 6.6 mg/L for S. capricornutum, C. vulgaris, and L. gibba, respectively. The 48-h immobility NOEC values for D. magna and D. pulicaria were 0.8 and 13.6 mg/L, respectively. In comparison to immobility, the 21-day lethality NOEC for D. magna was 5.3 mg/L. Based on effect (immobility) values, the most sensitive of all test organisms was D. magna. The most sensitive organism based on 50% inhibition of growth (IC(50)) was L. gibba, with an IC(50) value of 31.1 mg/L determined from wet weight. This is 4.3 times less than the LC(50) for D. pulicaria, which was 134 mg/L. Significant adverse effects (p < or = 0.05) were observed for all organisms in concentrations >134 mg/L. The results indicate that under laboratory conditions PFOS is acutely toxic to freshwater organisms at concentrations at or near 100 mg/L. Based on known environmental concentrations of PFOS, which occur in the low ng/L to low microg/L range, there is no apparent risk to freshwater systems. However, further work is required to investigate long-term effects in these and other freshwater organisms.

PMID: 12712289 [PubMed - in process]

Environ Sci Technol 2003 Mar 1;37(5):888-91

Human donor liver and serum concentrations of perfluorooctanesulfonate and other perfluorochemicals.

Olsen GW, Hansen KJ, Stevenson LA, Burris JM, Mandel JH.

3M Medical Department, 220-3W-05, St. Paul, Minnesota 55144, USA.

Perfluorooctanesulfonate (PFOS, CaF17SO3-) has been identified in the serum of nonoccupationally exposed humans and in serum and liver tissue in wildlife. The purpose of this investigation was to determine whether PFOS liver concentrations in humans are comparable to the approximate 30 ng/mL average serum concentrations reported in nonoccupationally exposed subjects. Thirty-one donors (16 male and 15 female, age range 5-74) provided serum and/or liver samples for analysis of PFOS and three other fluorochemicals: perfluorosulfonamide (PFOSA, C8F17SO2NH2), perfluorooctanoate (PFOA, C7F15CO2-), and perfluorohexanesulfonate (PFHxS, C6F13SO3-). Both sera and liver samples were extracted by ion-pair extraction and quantitatively assayed using high-performance liquid chromatography electrospray tandem mass spectrometry. Liver PFOS concentrations ranged from <4.5 ng/g (limit of quantitation, LOQ) to 57.0 ng/g. Serum PFOS concentrations ranged from <6.1 ng/mL (LOQ) to 58.3 ng/mL. Among the 23 paired samples, the mean liver to serum ratio was 1.3:1 (95% confidence interval 0.9:1-1.7:1). This liver to serum ratio is comparable to that reported in a toxicological study of cynomolgus monkeys, which had liver and serum concentrations 2-3 orders of magnitude higher than observed in these human donors. This information may be useful in human risk characterization for PFOS. Liver to serum ratios were not estimated for PFOA, PFHxS, and PFOSA as 90% of the human donor liver samples were determined to be less than the LOQ.

PMID: 12666917 [PubMed - in process]

J Occup Environ Med 2003 Mar;45(3):260-70

Epidemiologic assessment of worker serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA) concentrations and medical surveillance examinations.

Olsen GW, Burris JM, Burlew MM, Mandel JH.

Medical Dept., 3M Company, Mail Stop 220-3W-05, St. Paul, MN 55144, USA.

Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) is used to create applications for surfactants and paper, packaging, and surface (e.g., carpets, textiles) protectants. Such POSF-based products or their residuals may degrade or metabolize to PFOS (C8F17SO3-). PFOS concentrates in liver and serum and results in hypolipidemia as an early effect of cumulative dosages. Male and female employees of two perfluorooctanyl-manufacturing locations (Antwerp, Belgium and Decatur, Alabama) participated in a periodic medical surveillance program that included hematology, clinical chemistry, thyroid hormone, and urinalysis testing. Serum concentrations of PFOS and perfluorooctanoate (PFOA, C7F15CO2-, used as a fluoropolymer emulsifier) were measured via mass spectrometry methods. The mean serum PFOS and PFOA concentrations for 263 Decatur employees were 1.32 parts per million (ppm; geometric mean 0.91, range 0.06-10.06 ppm) and 1.78 ppm (geometric mean 1.13, range 0.04-12.70 ppm), respectively. Mean concentrations were approximately 50% lower among 255 Antwerp workers. Adjusting for potential confounding factors, there were no substantial changes in hematological, lipid, hepatic, thyroid, or urinary parameters consistent with the known toxicological effects of PFOS or PFOA in cross-sectional or longitudinal analyses of the workers' measured serum fluorochemical concentrations.

PMID: 12661183 [PubMed - in process]

Environ Toxicol Chem 2003 Mar;22(3):608-14

Perfluorooctane sulfonic acid in bib (Trisopterus luscus) and plaice (Pleuronectes platessa) from the Western Scheldt and the Belgian North Sea: distribution and biochemical effects.

Hoff PT, Van de Vijver K, Van Dongen W, Esmans EL, Blust R, De Coen WM.

Department of Biology, Research Unit Ecophysiology, Biochemistry and Toxicology, Antwerp University, Groenenborgerlaan 171, B-2020 Antwerp, Belgium.

A biomonitoring campaign was conducted in the Belgian North Sea and in the Western Scheldt (The Netherlands) with the primary goal to assess perfluorooctane sulfonic acid (PFOS) contamination and distribution in different biota. This study covers the results obtained for bib (Trisopterus luscus) and plaice (Pleuronectes platessa) and includes the assessment of some stress-related biochemical endpoints. Analysis of liver and muscle PFOS concentrations of both species provided evidence for the existence of a PFOS pollution gradient along the Western Scheldt with higher levels at the upstream locations and a lower degree of PFOS pollution at the marine locations. Cellular necrosis was studied by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum. Serum ALT but not serum AST was shown to correlate positively with the PFOS liver concentration in bib (r = 0.44, p < 0.05), indicating that PFOS might contribute to the induction of hepatic damage in bib in the area of study. Analysis of total carbohydrate, lipid, and protein content of bib liver tissue revealed a positive correlation between the protein content and the PFOS liver concentration (r = 0.55, p < 0.01). Whether this is due to induction of compensatory mechanisms, detoxification, or repair processes remains unclear.

PMID: 12627649 [PubMed - indexed for MEDLINE]

Aquat Toxicol 2003 Feb 26;62(4):349-59

Evaluation of the toxicological effects of perfluorooctane sulfonic acid in the common carp (Cyprinus carpio).

Hoff PT, Van Dongen W, Esmans EL, Blust R, De Coen WM.

Department of Biology, Research Unit Ecophysiology, Biochemistry and Toxicology, Antwerp University, Groenenborgerlaan 171, Belgium.

In the present study we evaluated the toxicological effects of a scarcely documented environmental pollutant, perfluorooctane sulfonic acid (PFOS), on selected biochemical endpoints in the common carp, Cyprinus carpio. Juvenile organisms were exposed to PFOS through a single intraperitoneal injection (liver concentrations ranging from 16 to 864 ng/g after 5 days of exposure) and after 1 and 5 days effects were assessed in liver and serum of the exposed organisms. The investigation of the hepatotoxicity of PFOS included the determination of the peroxisome proliferating potential (peroxisomal palmitoyl CoA oxidase and catalase activity) and the compounds influence on the average DNA basepair length (ABPL) by agarose gel electrophoresis. Total antioxidant activity (TAA), cholesterol and triglyceride levels were monitored in the serum. After 1 day of exposure the ABPL was significantly increased in the 270 and 864 ng/g treatment groups. After 5 days of exposure significant increases relative to the control were observed for the 16, 270 and 864 ng/g treatment groups. Enzyme leakage from the liver was investigated by measurement of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in the serum. At 561, 670 and 864 ng/g PFOS a significant increase in serum ALT activity became apparent after 5 days of exposure with values ranging from 159 to 407% relative to the control. For serum AST activity a significant increase for the 864 ng/g treatment group was observed with a value of 112% relative to the control. Determination of the polymorphonuclear leukocyte migration into liver tissue as assessed through myeloperoxidase (MPO) activity in liver, was used as an indicator for inflammation. It appeared that inflammation was not involved in the observed membranous enzyme leakage for the 561, 670 and 864 ng/g PFOS treatment groups. The results of this study suggest that PFOS induces inflammation-independent enzyme leakage through liver cell membranes that might be related to cell necrosis. Furthermore, results show that PFOS does not significantly affects serum antioxidant levels nor does it clearly induce peroxisome proliferation in carp. This study also points out that PFOS might interfere with homeostasis of the DNA metabolism. The results of these biochemical analyses were used to perform an initial hazard assessment study indicating that PFOS levels observed in tissues of wildlife populations could induce a clear rise in serum transaminase levels indicative for disruption of hepatocyte membrane integrity.

PMID: 12595174 [PubMed - indexed for MEDLINE]

Toxicology 2003 Feb 1;183(1-3):117-31

Sub-chronic dietary toxicity of potassium perfluorooctanesulfonate in rats.

Seacat AM, Thomford PJ, Hansen KJ, Clemen LA, Eldridge SR, Elcombe CR, Butenhoff JL.

3M Medical Department, Corporate Toxicology, 3M Center 220-2E-02, Saint Paul, MN 55133, USA.

Perfluorooctanesulfonate (PFOS) is a widely disseminated persistent compound found at low (part-per-billion) concentrations in serum and liver samples from humans and fish-eating wildlife. This study investigated the hypotheses that early hepatocellular peroxisomal proliferation and hepatic cellular proliferation are factors in chronic liver response to dietary dosing, that lowering of serum total cholesterol is an early clinical measure of response to treatment, and that liver and serum PFOS concentrations are proportional to dose and cumulative dose after sub-chronic treatment. PFOS was administered in diet as the potassium salt at 0, 0.5, 2.0, 5.0, and 20 parts per million (ppm) to Sprague Dawley rats for 4 or 14 weeks. At 4 weeks, effects included decreased serum glucose and an equivocal (<twofold) increase in hepatic palmitoyl CoA oxidase (PCoAO) activity in 20 ppm dose-group males and elevation of alanine aminotransferase (ALT) in 20 ppm dose-group females. At 14 weeks, the 20 ppm males had increased liver weight, decreased serum cholesterol, increased non-segmented neutrophils, and increased ALT. Relative liver weights and urea nitrogen were increased in both sexes at 14 weeks. Hepatocytic hypertrophy and cytoplasmic vacuolation were observed in the 5 or 20 ppm male and the 20 ppm female dose groups. An increase in hepatic PCoAO activity was not observed at 14 weeks, and the average hepatocyte proliferation index was not increased, although, individual animals had mild increases. Serum and liver PFOS concentrations were proportional to dose and cumulative dose. Serum concentrations were generally higher in females than in males. The liver-to-serum PFOS ratios ranged from approximately 3:1 to 12:1. After 14 weeks, the no-observed-adverse effect level (NOAEL) in males and females was 5 ppm. The NOAEL corresponded to mean serum PFOS concentrations of 44 ppm (microg/ml) in males and 64 ppm in females and mean liver PFOS concentrations of 358 ppm in males and 370 ppm in females. Results for this study:
(1) did not provide strong evidence for hepatocellular peroxisomal or cellular proliferation at the doses tested;
(2) suggested that lowering of serum total cholesterol may not be the earliest clinically-measurable response to treatment in the rat; and
(3) confirmed that serum and liver PFOS concentrations on repeated dosing are proportional to dose and cumulative dose.

PMID: 12504346 [PubMed - indexed for MEDLINE]

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