1995 - 1999 Abstracts


Abstracts on PFOS and PFOA for the following years:
1995 - 1999

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.

February 5, 1999.

3M. The Science of Organic Fluorochemistry 12 pages.

Full report available free at:

1999 Carcinogenesis Dec;20(12):2237-46

Effects of the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid, on apoptosis in human hepatoma HepG2 cells.

Shabalina IG, Panaretakis T, Bergstrand A, DePierre JW.

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

The effects of perfluorooctanoic acid (PFOA), a potent hepatocarcinogen and peroxisome proliferator in rodents, on human cells have not yet been examined. In the present study we demonstrate that treatment of human hepatoblastoma HepG2 cells with PFOA induces apoptosis, as well as perturbs the cell cycle. This apoptosis was characterized by electron microscopy, which revealed typical nucleosomal fragmentation (also observed as a 'DNA ladder' upon electrophoresis on agarose) and was quantitated using propidium iodide staining of cellular DNA and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. This process was dose- and time-dependent: apoptosis became manifest with 200 microM and maximal (45% of the cells) upon exposure to 450 microM PFOA for 24 h. Electrophoresis of the DNA from HepG2 cells exposed to 500 microM PFOA for 24 h or to 400 microM PFOA for 48 h revealed a smear typical of non-specific degradation. These findings indicate that in the presence of high concentrations of PFOA for long times, HepG2 cells undergo primary and secondary necrosis. Quantitation of trypan blue exclusion supported this conclusion. Flow cytometric analysis revealed that the cell cycle of HepG2 cells was perturbed by exposure to 50-150 microM PFOA. A 50 microM concentration resulted in a significant increase in the proportion of G(2)/M cells and, simultaneously, a decrease in the number of cells in the S phase, whereas treatment with 100 or 150 microM PFOA increased the proportion of cells in the G(0)/G(1) phase and decreased the number of cells in the G(2)/M and S phases. Simultaneous flow cytometric analysis of apoptosis-associated DNA strand breaks using the TUNEL procedure and of propidium iodide staining of cellular DNA revealed DNA breaks in HepG2 cells exposed to 150 microM PFOA, prior to nuclear fragmentation.

PMID: 10590214 [PubMed - indexed for MEDLINE]

1999 Chem Biol Interact Sep 30;122(2):73-87

Hypophysectomy and/or peroxisome proliferators strongly influence the levels of phase II xenobiotic metabolizing enzymes in rat testis.

Mehrotra K, Morgenstern R, Ahlberg MB, Georgellis A.

Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.

The objectives of the present work were to determine the influence of hypophysectomy and/or peroxisome proliferators (PP) on certain xenobiotic-metabolizing enzyme activities, i.e. glutathione transferases (GST), glutathione peroxidase (GPX), phenol sulphotransferases (pSULT), phenol UDP-glucuronosyl transferases (pUGT), catalase, NADP(H) quinone oxidoreductase (QR) and epoxide hydrolases (EH) in the rat testes. Adult male rats, hypophysectomized and their sham-operated controls, were treated for 10 days with clofibrate (0.5%), perfluorooctanoic acid (0.05%, PFOA), acetylsalicylic acid (1%, ASA) and di(2-ethylhexyl)phthalate (2%, DEHP) in their diet. The results show that, in addition to both body and testis weight, hypophysectomy caused dramatic changes in most of the xenobiotic-metabolizing enzyme activities, which have been measured here. The most pronounced effects were seen in cytosolic QR (2.2-fold increase), pUGT (95% reduction), pSULT (75% reduction), mitochondrial catalase (75% reduction), microsomal EH (70% reduction) and microsomal GST (55% reduction). Treatment with PP, i.e. perfluorooctanoic acid (PFOA), clofibrate, acetyl salicylic acid (ASA) and di(2-ethylhexyl)phthalate (DEHP) showed varied effects on the xenobiotic-metabolizing enzyme activities, the highest effects (10-60% reduction) were seen in sham-operated animals. These effects were not so pronounced or were not seen in hypophysectomized rats except for the case of PFOA treatment, which caused increases of enzyme activities. The highest increases were seen with microsomal GST (70%), GPX (75%) and cytosolic EH (75%). It is concluded from these experiments that the regulation of several xenobiotic-metabolizing enzymes in the rat testis is affected by the pituitary and/or pituitary hormones and that different peroxisome proliferators have variable effects on the levels of these xenobiotic-metabolizing enzymes. The general trend of reduction in enzyme activities implies that the testis is less protected under conditions that can perturb hormonal status.

PMID: 10528994 [PubMed - indexed for MEDLINE]

1999 Chem Biol Interact Mar 1;118(1):69-83

Alterations by perfluorooctanoic acid of glycerolipid metabolism in rat liver.

Kudo N, Mizuguchi H, Yamamoto A, Kawashima Y.

Faculty of Pharmaceutical Sciences, Josai University, Sakado, Saitama, Japan.

The effects of perfluorooctanoic acid (PFOA) feeding on hepatic levels of glycerolipids and the underlying mechanism were investigated. Feeding of rats with 0.01% of PFOA in the diet for 1 week caused an increase in the contents of phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) and triglyceride (TG), which were 2.2, 2.4, 2.4, 1.6 and 5.2 times over control, respectively, on the basis of whole liver. The activities of glycerol-3-phosphate acyltransferase, diacylglycerol kinase and PtdSer decarboxylase were significantly increased upon PFOA feeding, whereas the activities of CTP:phosphoethanolamine cytidylyltransferase and PtdEtn N-methyltransferase were decreased. On the other hand, the activity of CTP:phosphocholine cytidylyltransferase was not increased by PFOA. Upon PFOA feeding, hepatic level of 16:0-18:1 PtdCho was markedly increased and, by contrast, the levels of molecular species of PtdCho which contain 18:2 were decreased, resulting in the reduced concentration of molecular species of serum PtdCho containing 18:2. The increase in the level of hepatic 16:0-18:1 PtdCho seemed to be due to 3-fold increase in the activities of both delta9 desaturase and 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase. The mechanism by which PFOA causes the accumulation of glycerolipids in liver was discussed.

PMID: 10227579 [PubMed - indexed for MEDLINE]

1999 Biochim Biophys Acta Mar 25;1437(3):393-401

Perfluorooctanoic acid, a peroxisome-proliferating hypolipidemic agent, dissociates apolipoprotein B48 from lipoprotein particles and decreases secretion of very low density lipoproteins by cultured rat hepatocytes.

Okochi E, Nishimaki-Mogami T, Suzuki K, Takahashi A.

National Institute of Health Sciences, Kamiyoga 1-18-1, Setagaya-ku, Tokyo 158-8501, Japan.

The hypolipidemic effect is evoked by various peroxisome proliferators. Modulation of gene transcription via peroxisome proliferator-activated receptor (PPAR) is generally responsible for this effect. In addition, we have found a PPAR-independent mechanism in which fibrates, known peroxisome proliferators, decrease hepatic secretion of very low density lipoproteins (VLDL) through inhibition of phosphatidylcholine synthesis via methylation of phosphatidylethanolamine (PE) (T. Nishimaki-Mogami et al., Biochim. Biophys. Acta 1304 (1996) 21-31). In the present study, we show a novel mechanism by which perfluorooctanoic acid (PFOA), a potent peroxisome proliferator and inhibitor of PE methylation, exerts its hypolipidemic effect. PFOA (100 microM) added to the medium rapidly decreased the secretion of triglyceride by cultured rat hepatocytes, which was independent of the activity of cellular PE methylation. Analysis of the density of apoB secreted into the medium showed that PFOA decreased apoB48 in VLDL, but increased apoB48 in the bottom d>1.21 fraction. This lipid-poor apoB48 was also generated by incubating medium that had been harvested from control cells with PFOA, indicating that PFOA has the ability to dissociate apoB48 from lipoprotein particles. Exposure of cells to PFOA for 2 h prior to the experiment was sufficient to generate lipid-poor apoB48, indicating that PFOA exerted its effect intracellularly. Taken together, the data suggest that a strong interaction of PFOA with apoB48 disturbs the association of apoB48 with lipids in the process of intracellular VLDL assembly, thereby inhibiting VLDL secretion. This study shows that the mechanisms of hypolipidemic effect caused by various classes of peroxisome proliferators are diverse.

PMID: 10101272 [PubMed - indexed for MEDLINE]

1999 Toxicol Appl Pharmacol Dec 1;161(2):209-18

trans-Activation of PPARalpha and PPARgamma by structurally diverse environmental chemicals.

Maloney EK, Waxman DJ.

Division of Cell and Molecular Biology, Boston University, Boston, Massachusetts, 02215, USA.

A large number of industrial chemicals and environmental pollutants, including trichloroethylene (TCE), di(2-ethylhexyl)phthalate (DEHP), perfluorooctanoic acid (PFOA), and various phenoxyacetic acid herbicides, are nongenotoxic rodent hepatocarcinogens whose human health risk is uncertain. Rodent model studies have identified the receptor involved in the hepatotoxic and hepatocarcinogenic actions of these chemicals as peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor that is highly expressed in liver. Humans exhibit a weak response to these peroxisome proliferator chemicals, which in part results from the relatively low level of PPARalpha expression in human liver. Cell transfection studies were carried out to investigate the interactions of peroxisome proliferator chemicals with PPARalpha, cloned from human and mouse, and with PPARgamma, a PPAR isoform that is highly expressed in multiple human tissues and is an important regulator of physiological processes such as adipogenesis and hematopoiesis. With three environmental chemicals, TCE, perchloroethylene, and DEHP, PPARalpha was found to be activated by metabolites, but not by the parent chemical. A decreased sensitivity of human PPARalpha compared to mouse PPARalpha to trans-activation was observed with some (Wy-14, 643, PFOA), but not other, peroxisome proliferators (TCE metabolites, trichloroacetate and dichloroacetate; and DEHP metabolites, mono[2-ethylhexyl]phthalate and 2-ethylhexanoic acid). Investigation of human and mouse PPARgamma revealed the transcriptional activity of this receptor to be stimulated by mono(2-ethylhexyl)phthalate, a DEHP metabolite that induces developmental and reproductive organ toxicities in rodents. This finding suggests that PPARgamma, which is highly expressed in human adipose tissue, where many lipophilic foreign chemicals tend to accumulate, as well as in colon, heart, liver, testis, spleen, and hematopoietic cells, may be a heretofore unrecognized target in human cells for a subset of industrial and environmental chemicals of the peroxisome proliferator class. Copyright 1999 Academic Press.

PMID: 10581215 [PubMed - indexed for MEDLINE]

1999 J Occup Environ Med Sep;41(9):799-806

Serum perfluorooctane sulfonate and hepatic and lipid clinical chemistry tests in fluorochemical production employees.

Olsen GW, Burris JM, Mandel JH, Zobel LR.

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

The 3M Company manufactures fluorochemicals, which have as a precursor perfluorooctane sulfonyl fluoride (C8F17SO2F). These compounds may be expected to transform metabolically, to an undetermined degree, to perfluorooctane sulfonate (PFOS, C8F17SO3-) as an end-stage metabolite. Subchronic studies in rats and primates indicate a potential for cumulative toxicity with PFOS with the primary effect related to metabolic wasting with hypolipidemia as a consistent finding. Biennial medical surveillance has been offered to the company's fluorochemical production workers located in Decatur, Alabama, and Antwerp, Belgium. In 1995, the mean serum PFOS level, as measured by high-performance liquid chromatography mass spectrometry, for 178 male employees was 2.19 parts per million (ppm; range, 0.00 to 12.83 ppm), and in 1997, for 149 male employees, it was 1.75 ppm (0.10 to 9.93 ppm). Our analyses suggest that among these production employees, there were no substantial changes in serum hepatic enzymes, cholesterol, or lipoproteins associated with PFOS levels less than 6 ppm. It was not possible to derive inferences from the few employees who had serum PFOS levels > or = 6 ppm. These results may be due to the lower levels of serum PFOS measured among these production employees, compared to those suspected to cause effects in laboratory animals.

Publication Types: Multicenter Study

PMID: 10491796 [PubMed - indexed for MEDLINE]



Phosphate removal capacity of palustrine forested wetlands and adjacent uplands in Virginia.


Environmental Assessment Branch, U.S. Army Corps of Engineers, 26 Federal Plaza, New York, NY, 10278-0090, USA.

Abstract: BIOSIS COPYRIGHT: BIOL ABS. We examined the ability of soils in six nontidal palustrine forested wetlands (PFOs) in Virginia's Piedmont (PD) and Coastal Plain (CP) (n = 3 per physiographic province) to remove dissolved inorganic P from solution, and we compared the P sorption capacities of wetlands with those of streambanks (within wetlands) and adjacent uplands. We hypothesized that wetland soils would have higher P sorption capacities than streambank and upland soils due to the higher concentration of noncrystalline (oxa , Alo was correlated with P sorption capacity in wetland soils (r2 = 0.80), but so was soil organic matter (as estimated by mass loss on ignition (LOI)) (r2 = 0.78); in fact, Alo and organic matter were positively correlated in wetland soils (r2 = 0.84). In contrast, clay and silt content were the two soil parameters most highly positively correlated with P sorption capacity in upland soils (r2 = 0.87). Overall, these results suggest that differences in soil chemistry exist among landscape posit

CAS Registry Numbers:

1998 Int J Cancer Nov 9;78(4):491-5

Inhibition of gap junctional intercellular communication by perfluorinated fatty acids is dependent on the chain length of the fluorinated tail.

Upham BL, Deocampo ND, Wurl B, Trosko JE.

Department of Pediatrics and Human Development, Michigan State University, East Lansing 48824, USA.

Perfluorinated fatty acids (PFFAs), such as perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), are known peroxisome proliferators and hepatocarcinogens. A causal link between an increase in the oxidative stress by peroxisomes and tumor promotion has been proposed to explain the hepatocarcinogenicity of PFOA and PFDA. However, the down-regulation of gap junctional intercellular communication (GJIC) has also been linked to the tumor-promoting properties of many carcinogens. Therefore, the effect of PFFAs on GJIC in WB-rat liver epithelial cells was determined. The chain length of the PFFAs tested for an effect on GJIC ranged from 2 to 10, 16 and 18 carbons. Carbon lengths of 7 to 10 inhibited GJIC in a dose-response fashion, whereas carbon lengths of 2 to 5, 16 and 18 did not appreciably inhibit GJIC. Inhibition occurred within 15 min and was reversible, with total recovery from inhibition occurring within 30 min after the removal of the compound from the growth medium. This short time of inhibition suggests that GJIC was modified at the post-translational level. Also, this short time period was not long enough for peroxisome proliferation. The post-translational modification of the gap junction proteins was not a consequence of altered phosphorylation as determined by Western blot analysis. Perfluorooctanesulfonic acid also inhibited GJIC in a dose-response fashion similar to PFDA, indicating that the determining factor of inhibition was probably the fluorinated tail, which required 7-10 carbons. Our results suggest that PFFAs could potentially act as hepatocarcinogens at the level of gap junctions in addition to or instead of through peroxisome proliferation.

PMID: 9797139 [PubMed - indexed for MEDLINE]


1998 ENVIRONMENTAL SCIENCE & TECHNOLOGY; 32 (15). 2283-2287.

Defluorination of organofluorine sulfur compounds by Pseudomonas sp. strain D2.


Dep. Civil Environmental Engineering, Cent. Microbial Ecol., Michigan State Univ., East Lansing, MI 48824, USA.

BIOSIS COPYRIGHT: BIOL ABS. Little is known of the potential for biodegradation of fluorinated sulfonates. To evaluate this potential, the following model compounds were selected: difluoromethane sulfonate (DFMS), trifluoromethane sulfonate (TFMS), 2,2,2-trifluoroethane sulfonate (TES), perfluorooctane sulfonate (PFOS), and 1H,1H,2H,2H-perfluorooctane sulfonate (H-PFOS). A laboratory isolate designated Pseudomonas sp. strain D2 completely defluorinated DFMS under aerobic, sulfur-limiting conditions in a defined mineral medium. Strain D2 utilized DFMS as the sole source of sulfur, but not as a source of carbon or energy. DFMS utilization was inhibited by other forms of sulfur, and noncompetitive inhibition kinetics were observed, with Ki values of 3-4 muM for sulfate, sulfite, methane sulfonate, and cystine. Strain D2 was subsequently used to evaluate degradation of other fluorinated sulfonates. Growth and defluorination were only observed for those compounds containing hydrogen (TES and H-PFOS).

1998 Gen Pharmacol Aug;31(2):187-97

Mechanisms of peroxisome proliferation by perfluorooctanoic acid and endogenous fatty acids.

Intrasuksri U, Rangwala SM, O'Brien M, Noonan DJ, Feller DR.

Division of Pharmacology, College of Pharmacy, The Ohio State University, Columbus 43210, USA.

1. The effects of endogenous fatty acids and perfluorooctanoic acid (PFOA) and its analogs on peroxisomal acyl CoA oxidase (ACO) and microsomal laurate hydroxylase (LH) activities were evaluated in primary cultures of rat hepatocytes and activation of peroxisome proliferator-activated receptor alpha (PPARalpha) in CV-1 cells. The rank order for the stimulation of ACO activity in hepatocytes for selected compounds was PFOA >> octanoic acid>octanedioic acid, perfluorooctanol (inactive). Increases in ACO activity by PFOA, like those of ciprofibrate, were associated with a marked increase in peroxisome number and cytosolic occupancy volume. Maximal effects of ciprofibrate and PFOA on the stimulation of ACO activity were not additive, suggesting that these two compounds share a common pathway of peroxisome proliferation.
2. Saturated monocarboxylic acids of C4 to C18 chain length were inactive, and, among dicarboxylic acids, only small elevations (40-45%) in ACO activity were observed with the long-chain C12 and C16 dioic acids. Of the C18 fatty acids tested, only oleic and linoleic acids, at 1 mM, produced a two- to three-fold elevation in ACO and LH activities. In comparison with endogenous fatty acids, PFOA was more potent and exhibited a different time course and greater magnitude of stimulation of ACO and LH activities in cultured hepatocytes.
3. Addition of mitochondrial beta-oxidation inhibitors (3-mercaptopropionic and 2-bromooctanoic acids) did not alter ACO activity in the presence of octanoic acid or octanedioic acid; nor did they modify the stimulation of ACO activity by PFOA. The carnitine palmitoyltransferase I inhibitor 2-bromopalmitic acid produced a 2.5-fold increase in ACO stimulatory activity and reduced both ciprofibrate- and PFOA-mediated stimulations of ACO activity.
4. Cycloheximide treatment reduced PFOA- and ciprofibrate-induced ACO activities; however, the response to oleic acid was not blocked and increased slightly.
5. In rat and human PPARalpha transactivation assays, the rank order of activation was ciprofibrate > PFOA > oleic acid > or = octanoic acid > octanedioic acid or perfluorooctanol (inactive). PFOA, ciprofibrate and oleic acid were activators of rPPARalpha at concentrations that correlated favorably with the changes in ACO activity in cell culture. Octanoic acid did not increase ACO activity and was a weak activator of PPARalpha.
6. Our findings suggest that fatty acids such as oleic acid (endogenous fatty acids) and PFOA (a stable fatty acid) act through more than one pathway to increase ACO activity in rat hepatocytes. We conclude that the potent effects of PFOA are primarily mediated by a mechanism that includes the activation of liver PPARalpha.

PMID: 9688458 [PubMed - indexed for MEDLINE]

1998 J Occup Environ Med Jul;40(7):614-22

An epidemiologic investigation of reproductive hormones in men with occupational exposure to perfluorooctanoic acid.

Olsen GW, Gilliland FD, Burlew MM, Burris JM, Mandel JS, Mandel JH.

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

Perfluorooctanoic acid (PFOA), a potent synthetic surfactant used in industrial applications, is a peroxisome proliferator that has resulted in dose-related increases in hepatic, pancreatic acinar, and Leydig cell adenomas in laboratory animals. In addition, PFOA increased serum estradiol levels through the induction of hepatic aromatase activity. In 1993 and 1995, we conducted two cross-sectional studies of 111 and 80 production workers, respectively, and specifically measured their serum PFOA in relation to several reproductive hormones to determine whether such an effect occurs in humans. PFOA was not significantly associated with estradiol or testosterone in either year's study. A 10% increase in mean estradiol levels was observed among employees who had the highest levels of serum PFOA, although this association was confounded by body mass index. Neither was PFOA consistently associated with the other measured hormones. Our results provide reasonable assurance that, in this production setting, there were no significant hormonal changes associated with PFOA at the serum levels measured. Limitations of this investigation include its cross-sectional design, the few subjects exposed at the highest levels, and the lower levels of serum PFOA measured, compared with those levels reported to cause effects in laboratory animal studies.

PMID: 9675720 [PubMed - indexed for MEDLINE]

1998 Chem Res Toxicol May;11(5):428-40

Effects of peroxisome proliferators on rat liver phospholipids: sphingomyelin degradation may be involved in hepatotoxic mechanism of perfluorodecanoic acid.

Adinehzadeh M, Reo NV.

Departments of Biochemistry and Molecular Biology and of Physics, WSU Magnetic Resonance Laboratory, Wright State University, Cox Institute, Dayton, Ohio 45429, USA.

Perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), clofibrate, di(2-ethylhexyl)phthalate (DEHP), and Wy-14,643 represent a class of compounds known as peroxisome proliferators (PPs). Such compounds induce biogenesis of liver peroxisomes and cause a varying degree of hepatotoxicity and carcinogenesis in rodents. We examined the effects of these PPs on rat hepatic lipids and phospholipid profiles using phosphorus-31 NMR spectroscopy. All PPs caused a 25-57% increase in hepatic phospholipid content, while all but clofibrate increased the total lipid content by 26-156%. Treatments also influenced the composition of liver phospholipids. Phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEth) contents were significantly increased in all treatment groups. Most notably, PFDA caused the largest increase in PtdCho and PtdEth content (ca. 70%), while PFOA and Wy-14,643 were the only test compounds that influenced the PtdCho:PtdEth ratio. PFDA also caused an ca. 30% decrease in sphingomyelin (SphM) from 24 to 120 h postdose. SphM is a key lipid in signal transduction processes involved in apoptosis. Hydrolysis of SphM can be mediated through the action of tumor necrosis factor (TNF-alpha). We measured the TNF-alpha concentrations in rat sera at 24 h post-PFDA-exposure and found an 8-fold increase relative to vehicle-treated controls. These data demonstrate that an increase in the serum TNF-alpha level correlates with the time frame for the observed reduction in hepatic SphM. PFOA, a structurally similar compound, had no effect on hepatic SphM content, nor did it affect the serum TNF-alpha concentration. These effects may be related to differences in the tumorigenicity associated with these compounds. We postulate that PFDA activates the SphM signal transduction pathway via the release of TNF-alpha. This then stimulates cytotoxic responses and processes of apoptosis and may suppress cell proliferative and mitogenic responses.

PMID: 9585473 [PubMed - indexed for MEDLINE]




Source: EPA/OTS; Doc #000811744P

CAS Registry Numbers:

Order Number: NTIS/OTS0204929-3

Classification Code: TSCA Sect. 8E Rec 05/21/98

Year of Publication: 1998

Secondary Source ID: TSCATS/445338




Source: EPA/OTS; Doc #000811745Q

CAS Registry Numbers: 2795-39-3

Order Number: NTIS/OTS0204929-3

Classification Code: TSCA Sect. 8E Rec 05/21/98

Year of Publication: 1998

Secondary Source ID: TSCATS/445339




Source: EPA/OTS; Doc #000811746R

CAS Registry Number: 2795-39-3

Order Number: NTIS/OTS0204926-5

Classification Code: TSCA Sect. 8E Rec 05/21/98

Year of Publication: 1998

Secondary Source ID: TSCATS/445340

See full free report at

1998 CROATICA CHEMICA ACTA 71 (4)1075-1086


Adsorption of Ammonium Perfluorooctanoate at the Air–Water Interface

Geraldine A.Ottewill (a) and Ronald H.Ottewill (b)

a School of Chemistry, Physics and Radiography, University of Portsmouth, Portsmouth PO1 2DT, U.K.
b School of Chemistry, University of Bristol, Bristol BS8 1TS, U.K.

The adsorption of ammonium perfluorooctanoate has been investigated at the air-water interface as a function of surfactant concentration at various concentrations of ammonium chloride.The area
occupied by the surfactant ion was then calculated from the Gibbs equation with allowance for the presence of salt ions.Independently,the area per surfactant ion at the interface was determined
by the technique of neutron reflectiviy.Within experimental error the two sets of measurements were in good agreement.

1997 Chem Biol Interact May 2;104(2-3):131-45

Effects of peroxisome proliferators and/or hypothyroidism on xenobiotic-metabolizing enzymes in rat testis.

Mehrotra K, Morgenstern R, Lundqvist G, Becedas L, Bengtsson Ahlberg M, Georgellis A.

Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.

The objectives of the present work were to study the effects of certain peroxisome proliferators on xenobiotic-metabolizing enzyme activities in the testes of normal and hypothyroid rats, i.e. phenol sulfotransferases (pST), phenol UDP-glucuronosyl transferases (pUDPGT), glutathione transferases (GST), catalase, epoxide hydrolase (EH), glutathione peroxidase (GPX) and NAD(P)H quinone oxidoreductase (QR). Adult male rats (normal and hypothyroid) were treated for 10 days with clofibrate (0.5%), perfluorooctanoic acid (0.5%, PFOA), acetylsalisylic acid (1%, ASA) and di(2-ethylhexyl)phthalate (2%, DEHP) in their diet. The results show that treatment of normal rats with peroxisome proliferators dramatically affects the activities of xenobiotic-metabolizing enzymes (40-60% reduction). The highest effects are seen in catalase activity (50-60% with PFOA and ASA), pUDPGT (55% with PFOA), pST (55% with PFOA) and QR (50% with DEHP). These effects are not seen or are weaker after induction of hypothyroidism. Taken together, it is concluded that different classes of peroxisome proliferators have different effects on rat testicular xenobiotic-metabolizing enzymes.

PMID: 9212780 [PubMed - indexed for MEDLINE]

1997 Mol Cell Biochem Apr;169(1-2):143-7

Activated Kupffer cells attenuate the liver response to the peroxisome proliferator perfluorooctanoic acid.

Youssef J, Badr M.

University of Missouri-Kansas City 64108, USA.

It has been suggested that peroxisome proliferators stimulate Kupffer cells, an effect which may be involved in their mechanism of action. To evaluate this hypothesis, this study was designed to investigate the effect of stimulating Kupffer cells on basal as well as induced peroxisomal enzyme activity. Twenty four hours following treatment of male Sprague-Dawley rats with the peroxisome proliferating agent perfluorooctanoic acid (PFOA), in corn oil or with corn oil alone, hepatic peroxisomal beta-oxidation was 4.6 +/- 0.2 and 1.8 +/- 0.1 U/g liver, respectively. As expected, PFOA did not influence the catalase activity. Stimulating Kupffer cells in vivo by zymosan A (25 mg/kg, i.v.) prior to treatment with corn oil or PFOA diminished basal as well as PFOA-induced peroxisomal beta-oxidation by 20-35%. Activation of Kupffer cells by zymosan A also diminished catalase activity by over 60%. Furthermore, PFOA reduced blood colloidal carbon clearance by 35% within 2 h of its administration. The data suggest that activation of Kupffer cells exerts a negative effect on basal as well as PFOA-induced peroxisomal enzyme activities. Data also suggest that PFOA inhibits Kupffer cells. Activated Kupffer cells may indeed produce factors which interfere with normal hepatic peroxisomal functions and responses.

PMID: 9089641 [PubMed - indexed for MEDLINE]



Fluorinated organics in the biosphere.


Dep. Civil Environ. Eng., Mich. State Univ., East Lansing, MI 48824, USA.

Abstract: BIOSIS COPYRIGHT: BIOL ABS. The use of organofluorine compounds has increased throughout this century, and they are now ubiquitous environmental contaminants. Although generally viewed as recalcitrant because of their lack of chemical reactivity, many fluorinated organics are biologically active. Several questions surround their distribution, fate, and effects. Of particular interest is the fate of perfluoroalkyl substituents, such as the trifluoromethyl group. Most evidence to date suggest that such groups resist defluorination, yet they can confer significant biological activity. Certain volatile fluorinated compounds can be oxidized in the troposphere yielding nonvolatile compounds, such as trifluoroacetic acid. In addition, certain nonvolatile fluorinated compounds can be transformed in the biosphere to volatile compounds. Research is needed to assess the fate and effects of nonvolatile fluorinated organics, the fluorinated impurities present in commercial formulations, and the transformation [abstract truncated]

Fundamental and Applied Toxicology, Vol. 30, No. 1, pages 102-108, 37 references, 1996

The Direct Effect of Hepatic Peroxisome Proliferators on Rat Leydig Cell Function In Vitro

Liu RCM, Hahn C, Hurtt ME

The effects of 11 peroxisome proliferators on rat Leydig cells were investigated in-vitro. The compounds included 2,4-dichlorophenoxyacetic-acid (94-75-7) (2,4-D), acetylsalicylic-acid (530-75-6), ammonium-perfluorooctanoate (3825-26-1) (C8), ciprofibrate (52214-84-3), clofibric-acid (882-09-7), gemfibrozil (25812-30-0) (GEM), tiadenol (6964-20-1) (TIAD), tibric-acid (24358-29-0), trichloroacetic-acid (76-03-9), trichloroethylene (79-01-6), and Wyeth-14,643 (50892-23-4). Leydig cells were isolated from adult CD-rats, and cultured. After cells were incubated with one of the peroxisome proliferators for 21 hours, the medium was assayed for estradiol. Leydig cells were then cultured for an additional 3 hours with or without human chorionic gonadotropin (hCG), and the medium was assayed for testosterone. C8, GEM, and TIAD reduced the basal release of estradiol; the other compounds increased estradiol production. All but 2,4-D reduced hCG stimulated release of testosterone; 2,4-D reduced the testosterone response to 70% of control (not significant). The authors conclude that peroxisome proliferators may directly modify the steroidogenic function on Leydig cells in-vitro. The possible connection between the production of Leydig cell tumors in rats by some peroxisome proliferators and the induction of Leydig cell tumors in-vivo was considered.

1996 Toxicol Lett Jul;86(1):1-11

Perfluorodecanoic acid, a peroxisome proliferator, activates phospholipase C, inhibits CTP:phosphocholine cytidylyltransferase, and elevates diacylglycerol in rat liver.

Reo NV, Narayanan L, Kling KB, Adinehzadeh M.

Department of Biochemistry and Molecular Biology, Wright State University, Cox Institute, Dayton, Ohio 45429, USA.

Perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) are peroxisome proliferators that cause hepatotoxicity in rodents. This study shows that PFDA activates liver phospholipase C (PLC) and inhibits CTP:phosphocholine cytidylyltransferase (CT). PLC cytosolic and microsomal activities were increased 1.4- and 1.7-fold, respectively. CT activates were decreased to 58% (cytosol) and 36% (microsome) of control values. PFDA also caused a threefold increase in liver diacylglycerol (DAG) concentration. PFOA had no effect on the enzyme activities or DAG concentration. Together with previous results, these data suggest that PFDA activates a phosphatidylcholine-specific PLC causing an increase in liver phosphocholine and DAG. These effects are discussed in relation to cellular signalling processes that may provide a mechanism for PFDA-induced hepatotoxicity.

PMID: 8685914 [PubMed - indexed for MEDLINE]

1996 Am J Ind Med May;29(5):560-8

Serum perfluorooctanoic acid and hepatic enzymes, lipoproteins, and cholesterol: a study of occupationally exposed men.

Gilliland FD, Mandel JS.

Division of Environmental and Occupational Health, School of Public Health, University of Minnesota, Minneapolis, USA.

Perfluorooctanoic acid (PFOA) produces marked hepatic effects, including hepatomegaly, focal hepatocyte necrosis, hypolipidemia, and alteration of hepatic lipid metabolism in a number of animal species. In rodents, PFOA is a peroxisome proliferator, an inducer of members of the cytochrome P450 superfamily and other enzymes involved in xenobiotic metabolism, an uncoupler of oxidative phosphorylation, and may not be a cancer promoter. Although PFOA is the major organofluorine compound found in humans, little information is available concerning human responses to PFOA exposure. This study of 115 occupationally exposed workers examined the cross-sectional associations between PFOA and hepatic enzymes, lipoproteins, and cholesterol. The findings indicate that there is no significant clinical hepatic toxicity at the PFOA levels observed in this study. PFOA may modulate the previously described hepatic responses to obesity and xenobiotics.

PMID: 8732932 [PubMed - indexed for MEDLINE]

1996 Biol Pharm Bull May;19(5):765-7

Differences in the induction of carboxylesterase RL4 in rat liver microsomes by various perfluorinated fatty acids, metabolically inert derivatives of fatty acids.

Derbel M, Hosokawa M, Satoh T.

Laboratory of Biochemical Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, Chiba University, Japan.

Differences in the ability of metabolically inert peroxisome proliferators [perfluoro-n-decanoic acid (PFDA, C10), perfluoro-n-octanoic acid (PFOA, C8), perflorooctane sulfonic acid (PFOS, C8) and 1H,1H-pentadecafluoro-n-octanol (PFOL, C8)] to induce liver microsomal carboxylesterase RL4 in male rats were studied by evaluating changes in the RL4 content by immunoblot analysis with a specific antibody. The administration of PFOA, PFOS and PFOL markedly increase the content of carboxylesterase RL4. On the other hand, PFDA decreases PNPA, BUTA, and ISOC hydrolase activity, and slightly increases the carboxylesterase RL4 content.

PMID: 8741592 [PubMed - indexed for MEDLINE]

1995 Toxicology May 23;99(3):169-78

Characterization of hepatic responses of rat to administration of perfluorooctanoic and perfluorodecanoic acids at low levels.

Kawashima Y, Kobayashi H, Miura H, Kozuka H.

Faculty of Pharmaceutical Sciences, Josai University, Saitama, Japan.

Male rats were fed a diet that contained perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA) at concentrations ranging from 0.0025-0.04% (w/w) and from 0.00125-0.01% (w/w), respectively, for 1 week. The hepatic responses of the rats to PFOA and PFDA were examined. Upon the administration of PFOA and PFDA, three peroxisome proliferator-responsive parameters, peroxisomal beta-oxidation, microsomal 1-acylglycerophosphocholine (1-acyl-GPC) acyltransferase and cytosolic long-chain acyl-CoA hydrolase, were induced in a dose-dependent manner. A multiple regression analysis of the three parameters revealed that the data from rats treated with PFOA and PFDA shared one common line, indicating a marked correlation among the inductions of the three parameters. The activities of glutathione (GSH) S-transferases towards 1-chloro-2,4-dinitrobenzene (CDNB) and 1,2-dichloro-4-nitrobenzene (DCNB) were depressed by PFOA and PFDA. Significant inverse correlations were found between activities of GSH S-transferases and peroxisomal beta-oxidation. The administration of PFOA and PFDA significantly increased hepatic concentration of triacylglycerol. The perfluorocarboxylic acids at relatively high doses caused accumulation of cholesterol in liver. Electron microscopic studies showed that the administration of PFOA and PFDA caused an increase in cell size and proliferations of peroxisomes, and that the treatment of rats with PFDA at dietary concentration of 0.01% caused a marked increase in small lipid droplet in hepatocytes, indicative of hepatotoxic manifestations. The present results suggest that when PFOA and PFDA are administered at low levels, there are no differences between the properties of the perfluorocarboxylic acids as peroxisome proliferators, although the administration of PFDA at the doses exceeding a certain level becomes markedly toxic to hepatocytes.

PMID: 7610463 [PubMed - indexed for MEDLINE]

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