PFOS - PFOA: Adverse Effects
(Perfluoridated chemicals)
 
 

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PFOS - PFOA Index Page
Class Action Lawsuit

Research into the adverse health and ecological effects
of perfluorinated chemicals is in its infancy.


Many of the animal studies were done by 3M, its major producer, in the 1970s and late 1990s; and by DuPont, now the major producer of PFOA. Perfluoridated chemicals have widespread use and few published independent studies.

They have been in use for over 50 years.
In 1962 the Food and Drug Administration (FDA) granted final approval to Teflon cookware; and in 1967 they approved Zonyl, DuPont's leading brand of fluorinated telomers, for use in food packaging.

DuPont is facing a Class Action suit from residents in Ohio over the contamination of their drinking water supplies with the PFOA Ammonium perfluorooctanoate (commonly called C8). In 2001, DuPont settled out a court with a West Virginia couple who alleged that C8, dumped in a landfill near their farm, was responsible for the death of 260 cattle. Undaunted by lawsuits, DuPont, in 2002, began a new operation in Fayetteville, North Carolina, to produce C8.

On May 16, 2000, 3M "announced it is phasing out of the perfluorooctanyl chemistry... The affected product lines ... include many Scotchgard products, such as soil, oil and water repellent products; coatings used for oil and grease resistance on paper packaging; fire-fighting foams; and specialty components for other products..."

The alternative to C8 that 3M settled on is C4:

perfluorobutane sulfonate, or PFBS, a four-carbon cousin of the chemical in the old Scotchgard, as the building block for Scotchgard's new generation.
``For providing protection you almost can't do it without a fluoro-chemical, short of plastic slipcovers,'' said Michael Harnetty, vice president of 3M's protective materials division.
The new C4-based Scotchgard is completely safe, 3M says. The company adds that it has worked closely with the EPA and has performed more than 40 studies, which are confidential. The EPA won't release them.

Ref:
June 22, 2003. The Mercury News (California).Scotchgard working out recent stain on its business. Knight Ridder.

Until the announced phased-out in 2000 by 3M, PFOS chemicals were used in the production of a multitude of products and by various industries. Some products and industres may still be using them. A short list of uses:
stain-resistant fabric coatings
coatings for paper products
semiconductor chemicals
fire-fighting foams
mining and oil well surfactants
acid mist suppressants for metal plating and electronic etching baths
alkaline cleaners
floor polishes
photographic film
denture cleaners
shampoos
ant insecticides
(allowed to be used to be used up to the year 2016: Sulfluramid).


How we present Adverse Effects for PFOS and PFOA

Listed
at this site:
Due to length,
see separate effect pages

Apoptosis - (PFOA)

Bladder
- (PFOS - PFOA)

Endocrine:
Adrenal Gland
-
(PFOS - PFOA)
Breast - (PFOS)
Hypthalamus - (PFOS)
Ovary (Estrous) - (PFOS)
Pancreas
- (PFOS - PFOA)
Prostrate
- (PFOA)
Thymus -
(PFOS - PFOA)
Uterine - (PFOS)

Eye
- (PFOS - PFOA)
Genotoxic - (PFOA)

Heart
- (PFOS)
Kidney
- (PFOA)

Mesenteric Lymph Nodes
- (PFOS)
Salivary Gland - (PFOS)

Spleen
-
(PFOS - PFOA)

Teratogenic
- (PFOS - PFOA)

Body Weight Decrease - (PFOS - PFOA)

Blood - (PFOS - PFOA)

Bone
- (PFOS - PFOA)

Brain
- (PFOS - PFOA)

Cholesterol - (PFOS - PFOA)

Endocrine: Testes
- (PFOS - PFOA)

Endocrine: Thyroid
- (PFOS - PFOA)

G-Protein
- (PFOA)

Liver
- (PFOS - PFOA)

Lung - (PFOS - PFOA)

Reproduction / Developmental - (PFOS - PFOA)

Environmental - (PFOS)

Class Action Suit - (PFOA)

Contaimination Incident - (PFOA)


The use of high doses increases the likelihood that potentially significant toxic effects will be identified. Findings of adverse effects in any one species do not necessarily indicate such effects might be generated in humans. From a conservative risk assessment perspective however, adverse findings in animal species are assumed to represent potential effects in humans, unless convincing evidence of species specificity is available.

-- Food and Agricultural Organization of the United Nations


Note: This is not an exhaustive list. The review of data was performed
in 2003 and 2004.
When time allows more information will be added.

Apoptosis (click on for all fluorinated pesticides)

Abstract excerpt: "... one of the most potent rodent hepatocarcinogens, perfluorooctanoic acid (PFOA), induces apoptosis in human HepG2 cells in a dose- and time-dependent manner... In summary, we have delineated a ROS [reactive oxygen species] and mitochondria-mediated pathway for induction of apoptosis by PFOA."
Ref: 2001. Toxicol Appl Pharmacol May 15;173(1):56-64. Reactive oxygen species and mitochondria mediate the induction of apoptosis in human hepatoma HepG2 cells by the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid; by Panaretakis T, Shabalina IG, Grander D, Shoshan MC, DePierre JW.

Abstract excerpt: 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... 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.
Ref: 1999. Carcinogenesis Dec;20(12):2237-46. Effects of the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid, on apoptosis in human hepatoma HepG2 cells; by Shabalina IG, Panaretakis T, Bergstrand A, DePierre JW. Full report available free at:
http://carcin.oupjournals.org/cgi/content/full/20/12/2237

Abstract: 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.
Ref: 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; by Adinehzadeh M, Reo NV.

Bladder (click on for all fluorinated pesticides)

The toxicity profile of PFOS is similar among rats and monkeys. Repeated exposure results in hepatotoxicity and mortality; the dose-response curve is very steep for mortality. This occurs in animals of all ages, although the neonate may be more sensitive. In addition, a 2-year bioassay in rats has shown that exposure to PFOS results in hepatocellular adenomas and thyroid follicular cell adenomas; the hepatocellular adenomas do not appear to be related to peroxisome proliferation. Further work to elucidate the species differences in toxicokinetics and in the mode of action of PFOS will increase our ability to predict risk to humans. Epidemiologic studies have shown an association of PFOS exposure and the incidence of bladder cancer; further work is needed to understand this association.
Ref: November 21, 2002 report: Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

A retrospective cohort mortality study was performed on employees at the Cottage Grove, MN
plant which produces APFO (Gilliland and Mandel,1993). At this plant, APFO production was
limited to the Chemical Division.The cohort consisted of workers who had been employed at the
plant for at least 6 months between January 1947 and December 1983. Death certificates of all of the workers were obtained to determine cause of death. There was almost complete follow-up
(99.5%)of all of the study participants. ...
An update of this study was conducted to include the death experience of employees through
1997 (Alexander,2001a). The cohort consisted of 3992 workers. The eligibility requirement was
increased to 1 year of employment at the Cottage Grove plant, and the exposure categories were
changed to be more specific. Workers were placed into 3 exposure groups based on job history
information: definite PFOA exposure (n =492, jobs where cell generation, drying, shipping and
packaging of PFOA occurred throughout the history of the plant); probable PFOA exposure (n = 1685, other chemical division jobs where exposure to PFOA was possible but with lower or
transient exposures); and not exposed to fluorochemicals (n =1815,primarily non-chemical
division jobs). In this new cohort, 607 deaths were identified: 46 of these deaths were in the PFOA exposure group, 267 in the probable exposure group, and 294 in the non-exposed group. When all employees were compared to the state mortality rates, SMRs were less than 1 or only slightly higher for all of the causes of death analyzed. None of the SMRs were statistically significant at p =.05. The highest SMR reported was for bladder cancer (SMR =1.31,95%CI =0.42 – 3.05)). Five deaths were observed (3.83 expected).
Ref: April 10, 2003: Preliminary Risk Assessment of the Developmental Toxicity associated with Exposure to Perfluorooctanoic Acid and its Salts. US EPA Office of Pollution Prevention and Toxics. 63 pages.

Body Weight Decrease - Due to length, click here for effects page

Blood - Due to length, click here for effects page

Bone - Due to length, click here for effects page

Brain - Due to length, click here for effects page

Cholesterol - Due to length, click here for effects page

Class Action Suit - Due to length, click here

Contamination - Due to length, click here
This involves a "mysterious wasting disease" and death of 260 cattle in West Virginia. Linked to exposure to DuPont's landfilling of Ammonium perfluorooctanoate (C8) wastes in landfill near farm

Endocrine: Adrenal Gland (click on for all fluorinated pesticides)

Adverse signs of toxicity observed in Rhesus monkey studies included anorexia, emesis, diarrhea, hypoactivity, prostration, convulsions, atrophy of the salivary glands and the pancreas, marked decreases in serum cholesterol, and lipid depletion in the adrenals. The dose range for these effects was reported between 1.5-300 mg/kg/day. No monkeys survived beyond 3 weeks into treatment at 10 mg/kg/day or beyond 7 weeks into treatment at doses as low as 4.5 mg/kg/day.
Ref: November 21, 2002 report: Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

In the second study, Goldenthal et al. (1978a) administered rhesus monkeys, 2/sex/group, doses of 0, 0.5, 1.5 or 4.5 rng/kg/day PFOS (FC-95) in distilled water by gavage for 90 days... All monkeys in the 4.5 mg/kg/day group died or were sacrificed in extremis between week 5 and 7 of the study. Beginning on the first or second day of the study, these monkeys exhibited signs of gastrointestinal tract toxicity including anorexia, emesis, black stool and dehydration. All of the monkeys had decreased activity and just prior to death showed marked to severe rigidity, convulsions, generalized body trembling and prostration. The mean body weight decreased from 3.44 kg at the beginning of the study to 2.7 kg at week 5 . After 30 days of treatment, there was a significant reduction in serum cholesterol and a 50% reduction in serum alkaline phosphatase activity. At necropsy, mean organ weights were comparable among the control and treated monkeys. Histologic examination showed several treatment related lesions. All the male and females had marked diffuse lipid depletion in the adrenals. One male and two females had moderate diffuse atrophy of the pancreatic exocrine cells with decreased cell size and loss of zymogen granules. Two males and one female had moderate diffuse atrophy of the serous alveolar cells characterized by decreased cell size and loss of cytoplasmic granules.
Ref: Sulfornated Perfluorochemicals in the Environment: Sources, Dispersion, Fate and Effects. Prepared by 3M. March 1,2000.

3.5 Reproductive Toxicity Studies in Animals
York (2002) conducted an oral two-generation reproductive toxicity study of APFO, which is summarized below. Although this preliminary risk assessment focuses on developmental toxicity, the summary below of the two generation reproductive toxicity study includes all endpoints. Five groups of 30 Sprague-Dawley rats per sex per dose group were administered APFO by gavage at doses of 0,1,3,10, and 30 mg/kg/day six weeks prior to and during mating. Treatment of the F0 male rats continued until mating was confirmed,and treatment of the F0 female rats continued throughout gestation, parturition, and lactation....
Parental Males (F0)... No treatment-related effects were seen at necropsy or upon microscopic examination of the reproductive organs, with the exception of increased thickness and prominence of the zona glomerulosa and vacuolation of the cells of the adrenal cortex in the 10 and 30 mg/kg/day dosegroups.
F1 Males ... The absolute weight of the prostate, brain and left adrenal gland were significantly decreased in the 30 mg/kg/day dosage group. The ratios of the weights of the seminal vesicles, with and without fluid, liver and left and right kidneys to the terminal body weights were significantly increased in all treated groups... Histopathologic examination of the reproductive organs was unremarkable; however, treatment-related microscopic changes were observed in the adrenal glands of high-dose animals (cytoplasmic hypertrophy and vacuolation of the cells of the adrenal cortex) and in the liver of animals treated with 3,10,and 30 mg/kg/day (hepatocellular hypertrophy). No other treatment- related effects were reported.
Ref:
April 10, 2003: Preliminary Risk Assessment of the Developmental Toxicity associated with Exposure to Perfluorooctanoic Acid and its Salts. US EPA Office of Pollution Prevention and Toxics. 63 pages.

Endocrine: Breast (click on for all fluorinated pesticides)

3.5 Carcinogenicity. The chronic toxicity and carcinogenicity of perfluorooctane sulfonic acid potassium salt (PFOS; T-6295) have been studied in rats (3M, 2002). The results of the study show that PFOS is hepatotoxic and carcinogenic, inducing tumors of the liver, and of the thyroid and mammary glands. Based on the liver toxicity, the no-observed-adverse-effect level (NOAEL) for PFOS is considered to be 0.5 ppm in male rats and 2 ppm in female rats; the low observed-adverse-effect level (LOAEL) is 2 ppm in male rats and 5 ppm in female rats. In this study, groups of 40-70 male and female Crl:CD (SD)IGS BR rats were given PFOS in the diets at concentrations of 0.5, 2, 5, or 20 ppm for 104 weeks. A control group was given diets containing acetone, the vehicle. A recovery group was given the test material at 20 ppm for 52 weeks and was observed till death...

Table 3. Summary of carcinogenicity data of PFOS in rats (page 37)
Tumor: Mammary  Tumor incidence (%) - Females
0 0.5 ppm 2 ppm 5 ppm 20 ppm^^ 20 ppm^^
recovery#
Fibroadenoma/adenoma

38.3
(23/60)

60.0**
(30/50)
45.8
(22/48)
52.04
(26/50)
25
(15/60)
Carcinoma 18.3
(11/60)
24.0
(12/50)
31.2
(15/48)
22.0
(11/50)

23.3
(14/60

Combined 48.3
(29/60)
72.0**
(36/50)
64.6**
(31/48)
58,0
(29/50)
40.0
(24/60)
*Significant positive trend (P < 0.03).
** Significantly increased over the control (P < 0.05).
# Recovery group; after 52 weeks of treatment.
^^ Note from FAN: The last column is presented as it is in the Table. No explanation if offered to clarify.
Ref: November 21, 2002 report: Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.  
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Endocrine: Hypthalamus (click on for all fluorinated pesticides)

Abstract: 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.
Ref: Environ Health Perspect. 2003 Sep;111(12):1485-9. Neuroendocrine effects of perfluorooctane sulfonate in rats; by Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM.

Endocrine: Ovary (Estrous) (click on for all fluorinated pesticides)

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.
Ref: Environ Health Perspect. 2003 Sep;111(12):1485-9. Neuroendocrine effects of perfluorooctane sulfonate in rats; by Austin ME, Kasturi BS, Barber M, Kannan K, MohanKumar PS, MohanKumar SM.

Endocrine: Pancreas (click on for all fluorinated pesticides)

Adverse signs of toxicity observed in Rhesus monkey studies included anorexia, emesis, diarrhea, hypoactivity, prostration, convulsions, atrophy of the salivary glands and the pancreas, marked decreases in serum cholesterol, and lipid depletion in the adrenals. The dose range for these effects was reported between 1.5-300 mg/kg/day. No monkeys survived beyond 3 weeks into treatment at 10 mg/kg/day or beyond 7 weeks into treatment at doses as low as 4.5 mg/kg/day.
Ref: November 21, 2002 report: Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

In the second study, Goldenthal et al. (1978a) administered rhesus monkeys, 2/sex/group, doses of 0, 0.5, 1.5 or 4.5 rng/kg/day PFOS (FC-95) in distilled water by gavage for 90 days... All monkeys in the 4.5 mg/kg/day group died or were sacrificed in extremis between week 5 and 7 of the study. Beginning on the first or second day of the study, these monkeys exhibited signs of gastrointestinal tract toxicity including anorexia, emesis, black stool and dehydration. All of the monkeys had decreased activity and just prior to death showed marked to severe rigidity, convulsions, generalized body trembling and prostration... All the male and females had marked diffuse lipid depletion in the adrenals. One male and two females had moderate diffuse atrophy of the pancreatic exocrine cells with decreased cell size and loss of zymogen granules. Two males and one female had moderate diffuse atrophy of the serous alveolar cells characterized by decreased cell size and loss of cytoplasmic granules.
Ref: Sulfornated Perfluorochemicals in the Environment: Sources, Dispersion, Fate and Effects. Prepared by 3M. March 1,2000.

Abstract: Ammonium perfluorooctanoate is a potent synthetic surfactant used in industrial applications. It rapidly dissociates in biologic media to perfluorooctanoate [CF3(CF2)6CO2-], which is the anion of perfluorooctanoic acid [PFOA, CF3(CF2)6COOH]. PFOA is a peroxisome proliferator known to increase the incidence of hepatic, pancreas and Leydig cell adenomas in rats. The pancreas acinar cell adenomas may be the consequence of a mild but sustained increase of cholecystokinin as a result of hepatic cholestasis. Although no significant clinical hepatic toxicity was observed, PFOA was reported to have modulated hepatic responses to obesity and alcohol consumption among production workers. To further assess these hypotheses, we examined medical surveillance data of male workers involved in ammonium perfluorooctanoate production in 1993 (n=111), 1995 (n=80) and 1997 (n=74). Serum PFOA was measured by high-performance liquid chromatography mass spectrometry methods. Plasma cholecystokinin was measured (only in 1997) by the use of direct radioimmunoassay. Serum biochemical tests included hepatic enzymes, cholesterol and lipoproteins. Serum PFOA levels, by year, were: 1993 (mean 5.0 ppm, SD 12.2, median 1.1 ppm, range 0.0-80.0 ppm); 1995 (mean 6.8 ppm, SD 16.0, median 1.2 ppm, range 0.0-114.1 ppm); and 1997 (mean 6.4 ppm, SD 14.3, median 1.3 ppm, range 0.1-81.3 ppm). Cholecystokinin values (mean 28.5 pg/ml, SD 17.1, median 22.7 pg/ml, range 8.8-86.7 pg/ml) approximated the assay's reference range (up to 80 pg/ml) for a 12 hour fast and were negatively, not positively, associated with employees' serum PFOA levels. Our findings continue to suggest there is no significant clinical hepatic toxicity associated with PFOA levels as measured in this workforce. Unlike a previously reported observation, PFOA did not appear to modulate hepatic responses to either obesity or alcohol consumption. Limitations of these findings include:
1) the cross-sectional design as only 17 subjects were common for the three surveillance years;
2) the voluntary participation that ranged between 50 and 70 percent; and
3) the few subjects with serum levels > or = 10 ppm.
Ref: 2000. Drug Chem Toxicol Nov;23(4):603-20. Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers; by Olsen GW, Burris JM, Burlew MM, Mandel JH. Medical Department, 3M Company, St. Paul, MN 55144-1000, USA.

Endocrine: Prostate (click on for all fluorinated pesticides)

Perfluorooctanoic acid (PFOA) has been found at low levels (10 to 100 parts per billion) in sera of the general population and at higher levels in occupationally exposed workers. Although PFOA has been reported to be a promoter of rodent hepatocarcinogenesis and to alter reproductive hormones in humans and rodents, there is little information on human health effects associated with PFOA exposure. The present study examined the relationship between PFOA and mortality using a retrospective cohort mortality design. The cohort consisted of 2788 male and 749 female workers employed between 1947 and 1983 at a plant that produced PFOA. The all-causes standardized mortality ratio was .75 (95% confidence interval [CI], .56 to .99) for women and .77 (95% CI, .69 to .86) for men. Among men the cardiovascular standardized mortality rate was .68 (95% CI, .58 to .80) and the all-gastrointestinal diseases was .57 (95% CI, .29 to .99). There was no significantly increased cause-specific standardized mortality ratio for either men or women. Ten years of employment in exposed jobs was associated with a 3.3-fold increase (95% CI, 1.02 to 10.6) in prostate cancer mortality compared to no employment in PFOA production. There were only six prostate cancer deaths overall and four among the exposed workers; thus, the results must be interpreted cautiously. If prostate cancer mortality is related to PFOA, PFOA may increase prostate cancer mortality by altering reproductive hormones in male workers.
Ref: 1993. J Occup Med Sep;35(9):950-4. Mortality among employees of a perfluorooctanoic acid production plant; by Gilliland FD, Mandel JS.

Abstract excerpt: Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are synthetic surfactants used in Japan. An epidemiological study of workers exposed to PFOA revealed a significant increase in prostate cancer mortality. A cross-sectional study of PFOA-exposed workers showed that PFOA perturbs sex hormone homeostasis. We analyzed their concentrations in surface water samples collected from all over Japan by LC/MS with a solid phase extraction method... Systematic searches of Yodo and Kanzaki Rivers revealed two highly contaminated sites, a public-water-disposal site for PFOA and an airport for PFOS. The former was estimated to release 18 kg of PFOA/d. PFOA in drinking water in Osaka city [40 (1.07) ng/L] was significantly higher than in other areas. The present study confirms that recognizable amounts of PFOA are released in the Osaka area and that people are exposed to PFOA through drinking water ingestion.
Ref: 2004. J Occup Health. Jan;46(1):49-59. Perfluorooctanoate and perfluorooctane sulfonate concentrations in surface water in Japan; by Saito N, Harada K, Inoue K, Sasaki K, Yoshinaga T, Koizumi A.

Endocrine: Testes - Due to length, click here for effects page

Endocrine: Thymus (click on for all fluorinated pesticides)

Abstract: The effects of peroxisome proliferators on the immune system of male C57B1/6 mice have been investigated. Significant atrophy of the thymus and spleen was observed in animals treated with potent peroxisome proliferators (e.g. perfluorooctanoic acid (PFOA), di(2-ethylhexyl)phthalate (DEHP), Wy-14643 and nafenopin), whereas the effects of a moderate peroxisome proliferator (i.e. acetylsalicylic acid (ASA)) were relatively weak. The time course of thymic and splenic atrophy caused by PFOA was found to resemble the time course of the increase in liver weight and of peroxisome proliferation... Interestingly, in vitro exposure to PFOA for up to 24 h did not produce analogous effects in either thymocytes or splenocytes. Thus, the thymic and splenic atrophy caused by PFOA appears to involve an indirect pathway."
Ref: 2000. Clin Exp Immunol Nov;122(2):219-26. Effects of peroxisome proliferators on the thymus and spleen of mice; by Yang Q, Xie Y, Depierre JW.

3.5 Reproductive Toxicity Studies in Animals
York (2002) conducted an oral two-generation reproductive toxicity study of APFO, which is summarized below. Although this preliminary risk assessment focuses on developmental toxicity, the summary below of the two generation reproductive toxicity study includes all endpoints. Five groups of 30 Sprague-Dawley rats per sex per dose group were administered APFO by gavage at doses of 0,1,3,10, and 30 mg/kg/day six weeks prior to and during mating. Treatment of the F0 male rats continued until mating was confirmed,and treatment of the F0 female rats continued throughout gestation, parturition, and lactation....
Parental Males (F0)... At necropsy, statistically significant reductions in terminal body weights
were seen at 3,10,and 30 mg/kg/day. Absolute weights of the left and right epididymides, left cauda epididymis, seminal vesicles (with and without fluid), prostate, ,left and right adrenals, spleen, and thymus were also significantly reduced at 30 mg/kg/day... All organ weight-to-terminal body weight and ratios were significantly increased in all treated groups...
F1 Males ...
The absolute weight of the thymus was also significantly decreased in the 10 and 30
mg/kg/day dose groups...
The ratios of the spleen weight-to-brain weight were significantly decreased at 1 mg/kg/day and higher, and the ratios of the thymus weight-to-brain weight were significantly decreased at 10 and 30 mg/kg/day...
Ref:
April 10, 2003: Preliminary Risk Assessment of the Developmental Toxicity associated with Exposure to Perfluorooctanoic Acid and its Salts. US EPA Office of Pollution Prevention and Toxics. 63 pages.

In the rat subchronic study, Goldenthal et al. (1978b) administered CD rats, 5/sex/group, dietary
levels of 0, 30, 100, 300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males weighed 196-232 g and the females weighed 165-206 g at study initiation. The dietary levels were equivalent to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were sacrificed after 90 days of treatment and a gross necrospy was conducted... All of the rats in the 300, 1000 and 3000 ppm groups died. Death occurred between days 13-25 and days 18-28 for the males and females, respectively, in the 300 ppm group...
The rats in all groups showed signs of toxicity including emaciation, convulsions following
handling, hunched back, red material around the eyes, yellow material around the anogenital
region, increased sensitivity to external stimuli, reduced activity and moist red material around
the mouth or nose. Three males and two females in the 100 ppm group died prior to scheduled sacrifice. Two of the males and the two females died during week 5 and the third male died during week 11 of the study... All rats in the 30 ppm group survived until the end of the study... Histologic examination also showed lesions in all treated groups. Centrilobular to midzonal cytoplasmic hypertrophy of hepatocytes and focal necrosis was observed in the liver; the incidence and relative severity were greater in the males. In addition, especially among rats in the 300, 1000 and 3000 ppm groups, treatment related histologic lesions were noted in the primary (thymus, bone marrow) and secondary (spleen, mesenteric lymph nodes) lymphoid organs, stomach, intestines, muscle and skin. In the thymus, this consisted of depletion in the number and size of the lymphoid follicles and in the bone marrow hypocellularity was noted. The spleen was slightly atrophied with a corresponding decrease in the size and number of lymphoid follicles and cells and a similar depletion was noted in the mesenteric lymph nodes.
Ref: August 31, 2000. MEMORANDUM. SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed, Branch Chief, Existing Chemical Assessment Branch, Risk Assessment Division (7403). THRU: Oscar Hernandez , Division Director, Risk Assessment Division (7403). TO: Charlie Auer, Division Director, Chemical Control Division (7405).

Endocrine: Thyroid - Due to length, click here for effects page

Endocrine: Uterine (click on for all fluorinated pesticides)

In a second prenatal developmental toxicity study, groups of 25 pregnant Sprague-Dawley rats were administered 0, 1, 5, and 10 mg/kg/day PFOS in corn oil by gavage on gestation days (GD) 6-15 (Wetzel, 1983). Sexually mature Sprague-Dawley rats, one per sex per cage, were paired until confirmation of mating or until two weeks had elapsed. Mating was confirmed by daily vaginal examinations for the presence and viability of sperm or the presence of a copulatory plug. The day of confirmation of mating was designated as day 0 of gestation. Doses were adjusted according to the most recently recorded body weight measurements. Dams were observed twice daily for signs of mortality and moribundity and once daily for clinical signs of toxicity. Individual body weights and food consumption were recorded on GD 6, 8, 12, 16, and 20. Animals were sacrificed on GD 20 by CO2 asphyxiation and the fetuses were delivered by cesarean section on GD 20. A gross necropsy was performed on all dams... Evidence of maternal toxicity, that was observed at the 5 and 10 mg/kg/day dose groups both during and following treatment and considered to be treatment-related, consisted of hunched posture, anorexia, bloody vaginal discharge, uterine stains, alopecia, rough haircoat, and bloody crust. Significant decreases in mean body weight gains during GD 6-8, 6-16, and 0-20 were also observed at the 5 and 10 mg/kg/day dose groups. These reductions were considered to be treatment-related since mean body weight gains were greater than controls during the post-exposure period (GD 16-20). Significant decreases in mean total food consumption were observed on GD 17-20 in the10 mg/kg/day dose group, and on GD 7-16 and 0-20 in both the 5 and 10 mg/kg/day dose groups. The mean gravid uterine weight in the 10 mg/kg/day dose group was significantly lower when compared with controls. The mean terminal body weights minus the gravid uterine weights were lower in all treated groups, with significant decreases at 5 and 10 mg/kg/day. High-dose animals also exhibited an increased incidence in gastrointestinal lesions. No significant differences were observed in pregnancy rates, number of corpora lutea, and number and placement of implantation sites among treated and control groups. Two dams in the 10 mg/kg/day dose group were found dead on GD 17. Under the conditions of the study, a NOAEL of 1 mg/kg/day and a LOAEL of 5 mg/kg/day for maternal toxicity were indicated.
Ref: November 21, 2002 report:
Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Eye (click on for all fluorinated pesticides)

" DuPont tested for and found PFOA in the blood of female plant workers in Parkersburg. The company followed and documented pregnancy outcomes in exposed workers. Two of seven children born to female plant workers between 1979 and 1981 had birth defects, one an “unconfirmed” eye and tear duct defect, and one a nostril and eye defect. [Dupont Document] In 1981 fifty women were reassigned in the plant."
Ref: Environmental Working Group.
2003 report: PFCs: a family of chemicals that contaminate the planet. Part 4: PFC Health Concerns

3.6 Developmental Toxicity. Three prenatal developmental toxicity studies of PFOS have been conducted, two studies in rats and one study in rabbits. In addition, preliminary results are available for developmental toxicity studies in rats and mice. The first study administered four groups of 22 time-mated Sprague-Dawley rats 0, 1, 5, and 10 mg/kg/day PFOS in corn oil by gavage on gestation days (GD) 6-15 (Gortner, 1980). Doses were adjusted according to body weight. Dams were monitored on GD 3-20 for clinical signs of toxicity. Individual body weights were recorded on GD 3, 6, 9, 12, 15, and 20. Animals were sacrificed on GD 20 by cervical dislocation and the ovaries, uteri and contents were examined for the number of corpora lutea, number of viable and non-viable fetuses, number of resorption sites, and number of implantation sites... The most notable sign of developmental toxicity observed in all dose groups consisted of abnormalities of the lens of the eye, which was not seen in controls. The proportion of fetuses with the lens abnormality in one or both lenses was significantly higher in the high dose group. All eye abnormalities appeared to be localized to the area of the embryonal lens nucleus, although a variety of morphological appearances were present within that location. According to the authors, this abnormality appeared to be an arrest in development of the primary lens fibers forming the embryonal lens nucleus. Secondary lens fiber development progressed normally except immediately surrounding the abnormal embryonal nucleus. Under the conditions of the study, a LOAEL for developmental toxicity of 1 mg/kg/day was indicated; a developmental NOAEL could not be established.
Ref: November 21, 2002 report:
Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Genotoxic (click on for all fluorinated pesticides)

Abstract excerpt: 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... 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.
Ref: 1999. Carcinogenesis Dec;20(12):2237-46. Effects of the rodent peroxisome proliferator and hepatocarcinogen, perfluorooctanoic acid, on apoptosis in human hepatoma HepG2 cells; by Shabalina IG, Panaretakis T, Bergstrand A, DePierre JW. Full report available free at:
http://carcin.oupjournals.org/cgi/content/full/20/12/2237

Abstract: To elucidate the relationship between peroxisome proliferation by perfluorinated compounds and oxidative DNA damage, perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDA), perfluorobutyric acid (PFBA) and perfluorooctane (PFO) were administered to 6-week-old F-344 male rats. After a single intraperitoneal (i.p.) injection of PFOA, PFBA or PFO in corn oil at a dose of 100 mg/kg, significant increases of liver weight and 8-hydroxydeoxyguanosine (8-OH-dG) levels in liver DNA were observed in PFOA-treated rats. Oral administration of powdered diet containing 0.02% PFOA or 0.01% PFDA for 2 weeks resulted in significant increases of liver weight and 8-OH-dG levels in liver DNA in rats given both chemicals. On the other hand, no increase in 8-OH-dG levels in kidney DNA was found in either of the studies. Our results demonstrate that, as with other peroxisome proliferators (phthalic ester plasticizers and hypolipidemic drugs), PFOA and PFDA induced peroxisome proliferation also leads to organ specific oxidative DNA damage.
Ref: 1991. Cancer Lett Apr;57(1):55-60. Short-term exposure to the peroxisome proliferators, perfluorooctanoic acid and perfluorodecanoic acid, causes significant increase of 8-hydroxydeoxyguanosine in liver DNA of rats; by Takagi A, Sai K, Umemura T, Hasegawa R, Kurokawa Y.

G-Protein - Due to length, click here for effects page

Heart (click on for all fluorinated pesticides)

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.
Ref: Toxicol Sci 2003 May 28; Exposure to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse. I. Maternal and Prenatal Evaluations; by 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, North Carolina 27711, USA.)

Kidney (click on for all fluorinated pesticides)

Abstract: Response of rat kidney to the challenges by perfluorooctanoic acid (PFOA) was studied using microsomal 1-acyglycerophosphocholine (1-acyl-GPC) acyltransferase as a parameter. Marked induction of the enzyme was brought about in kidney of male rats, whereas the induction in kidney of female rats was far less pronounced. The sex-related difference in the response of kidney to PFOA was much more marked than those seen with p-chlorophenoxyisobutyric acid (clofibric acid) or 2,2'-(decamethy-lenedithio)diethanol (tiadenol). Hormonal manipulations revealed that the sex-related difference in the response of kidney to PFOA was strongly dependent on the state of gonadal hormones of rats. Even after a prolonged administration of PFOA for up to 26 weeks, this sex-related difference was still evident. Induction of peroxisomal beta-oxidation was brought about concurrently with microsomal 1-acyl-GPC acyltransferase and a high correlation was confirmed between the inductions of these two parameters.
Ref: 1991. Biochem Pharmacol Oct 24;42(10):1921-6. Induction by perfluorooctanoic acid of microsomal 1-acylglycerophosphocholine acyltransferase in rat kidney. Sex-related difference; by Kawashima Y, Matsunaga T, Uy-Yu N, Kozuka H.

3.5 Reproductive Toxicity Studies in Animals
York (2002) conducted an oral two-generation reproductive toxicity study of APFO, which is summarized below. Although this preliminary risk assessment focuses on developmental toxicity, the summary below of the two generation reproductive toxicity study includes all endpoints. Five groups of 30 Sprague-Dawley rats per sex per dose group were administered APFO by gavage at doses of 0,1,3,10, and 30 mg/kg/day six weeks prior to and during mating. Treatment of the F0 male rats continued until mating was confirmed,and treatment of the F0 female rats continued throughout gestation, parturition, and lactation....
F1 Males ...
... Necroscopic examination revealed statistically significant treatment-related effects at 3,10,and 30 mg/kg/day ranging from tan areas in the lateral and median lobes of the liver to moderate to slight dilation of the pelvis of one or both kidneys... The absolute weights of the left and/or right kidneys were significantly increased in the 1 and 3 mg/kg/day dose groups and significantly decreased in the 30 mg/kg/day dose group...
Ref:
April 10, 2003: Preliminary Risk Assessment of the Developmental Toxicity associated with Exposure to Perfluorooctanoic Acid and its Salts. US EPA Office of Pollution Prevention and Toxics. 63 pages.

Liver - Due to length, click here for effects page

Lung - Due to length, click here for effects page

Mesenteric Lymph Nodes (click on for all fluorinated pesticides)

In the rat subchronic study, Goldenthal et al. (1978b) administered CD rats, 5/sex/group, dietary
levels of 0, 30, 100, 300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males weighed 196-232 g and the females weighed 165-206 g at study initiation. The dietary levels were equivalent to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were sacrificed after 90 days of treatment and a gross necrospy was conducted... All of the rats in the 300, 1000 and 3000 ppm groups died. Death occurred between days 13-25 and days 18-28 for the males and females, respectively, in the 300 ppm group...
The rats in all groups showed signs of toxicity including emaciation, convulsions following
handling, hunched back, red material around the eyes, yellow material around the anogenital
region, increased sensitivity to external stimuli, reduced activity and moist red material around
the mouth or nose. Three males and two females in the 100 ppm group died prior to scheduled sacrifice. Two of the males and the two females died during week 5 and the third male died during week 11 of the study... All rats in the 30 ppm group survived until the end of the study... Histologic examination also showed lesions in all treated groups. Centrilobular to midzonal cytoplasmic hypertrophy of hepatocytes and focal necrosis was observed in the liver; the incidence and relative severity were greater in the males. In addition, especially among rats in the 300, 1000 and 3000 ppm groups, treatment related histologic lesions were noted in the primary (thymus, bone marrow) and secondary (spleen, mesenteric lymph nodes) lymphoid organs, stomach, intestines, muscle and skin. In the thymus, this consisted of depletion in the number and size of the lymphoid follicles and in the bone marrow hypocellularity was noted. The spleen was slightly atrophied with a corresponding decrease in the size and number of lymphoid follicles and cells and a similar depletion was noted in the mesenteric lymph nodes.
Ref: August 31, 2000. MEMORANDUM. SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed, Branch Chief, Existing Chemical Assessment Branch, Risk Assessment Division (7403). THRU: Oscar Hernandez , Division Director, Risk Assessment Division (7403). TO: Charlie Auer, Division Director, Chemical Control Division (7405).

Reproduction / Developmental - Due to length, click here for effects page

Salivary Gland (click on for all fluorinated pesticides)

Adverse signs of toxicity observed in Rhesus monkey studies included anorexia, emesis, diarrhea, hypoactivity, prostration, convulsions, atrophy of the salivary glands and the pancreas, marked decreases in serum cholesterol, and lipid depletion in the adrenals. The dose range for these effects was reported between 1.5-300 mg/kg/day. No monkeys survived beyond 3 weeks into treatment at 10 mg/kg/day or beyond 7 weeks into treatment at doses as low as 4.5 mg/kg/day.
Ref: November 21, 2002 report: Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Spleen (click on for all fluorinated pesticides)

The effects of peroxisome proliferators on the immune system of male C57B1/6 mice have been investigated. Significant atrophy of the thymus and spleen was observed in animals treated with potent peroxisome proliferators (e.g. perfluorooctanoic acid (PFOA), di(2-ethylhexyl)phthalate (DEHP), Wy-14643 and nafenopin), whereas the effects of a moderate peroxisome proliferator (i.e. acetylsalicylic acid (ASA)) were relatively weak. The time course of thymic and splenic atrophy caused by PFOA was found to resemble the time course of the increase in liver weight and of peroxisome proliferation... Interestingly, in vitro exposure to PFOA for up to 24 h did not produce analogous effects in either thymocytes or splenocytes. Thus, the thymic and splenic atrophy caused by PFOA appears to involve an indirect pathway."
Ref: 2000. Clin Exp Immunol Nov;122(2):219-26. Effects of peroxisome proliferators on the thymus and spleen of mice; by Yang Q, Xie Y, Depierre JW.

In the rat subchronic study, Goldenthal et al. (1978b) administered CD rats, 5/sex/group, dietary
levels of 0, 30, 100, 300, 1000 or 3000 ppm PFOS (FC-95) for 90 days. The males weighed 196-232 g and the females weighed 165-206 g at study initiation. The dietary levels were equivalent to doses of 0, 2, 6, 18, 60 and 200 mg/kg/day... The rats were sacrificed after 90 days of treatment and a gross necrospy was conducted... All of the rats in the 300, 1000 and 3000 ppm groups died. Death occurred between days 13-25 and days 18-28 for the males and females, respectively, in the 300 ppm group...
The rats in all groups showed signs of toxicity including emaciation, convulsions following
handling, hunched back, red material around the eyes, yellow material around the anogenital
region, increased sensitivity to external stimuli, reduced activity and moist red material around
the mouth or nose. Three males and two females in the 100 ppm group died prior to scheduled sacrifice. Two of the males and the two females died during week 5 and the third male died during week 11 of the study... All rats in the 30 ppm group survived until the end of the study... Histologic examination also showed lesions in all treated groups. Centrilobular to midzonal cytoplasmic hypertrophy of hepatocytes and focal necrosis was observed in the liver; the incidence and relative severity were greater in the males. In addition, especially among rats in the 300, 1000 and 3000 ppm groups, treatment related histologic lesions were noted in the primary (thymus, bone marrow) and secondary (spleen, mesenteric lymph nodes) lymphoid organs, stomach, intestines, muscle and skin. In the thymus, this consisted of depletion in the number and size of the lymphoid follicles and in the bone marrow hypocellularity was noted. The spleen was slightly atrophied with a corresponding
decrease in the size and number of lymphoid follicles and cells
and a similar depletion was noted in the mesenteric lymph nodes.
Ref: August 31, 2000. MEMORANDUM. SUBJECT: Hazard Assessment of PFOS. FROM: Jennifer Seed, Branch Chief, Existing Chemical Assessment Branch, Risk Assessment Division (7403). THRU: Oscar Hernandez , Division Director, Risk Assessment Division (7403). TO: Charlie Auer, Division Director, Chemical Control Division (7405).

Teratogenic (click on for all fluorinated pesticides)

" DuPont tested for and found PFOA in the blood of female plant workers in Parkersburg. The company followed and documented pregnancy outcomes in exposed workers. Two of seven children born to female plant workers between 1979 and 1981 had birth defects, one an “unconfirmed” eye and tear duct defect, and one a nostril and eye defect. [Dupont Document] In 1981 fifty women were reassigned in the plant."
Ref: Environmental Working Group.
2003 report: PFCs: a family of chemicals that contaminate the planet. Part 4: PFC Health Concerns

Abstract: 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.
Ref: Toxicol Sci 2003 May 28; Exposure to Perfluorooctane Sulfonate During Pregnancy in Rat and Mouse. I. Maternal and Prenatal Evaluations; by 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, North Carolina 27711, USA.)

• Note from FAN:

Anasarca refers to generalized edema, in its most severe form. There is an accumulation of fluid in subcutaneous tissues, internal organs, and body cavities. It typically occurs during the course of nephrotic syndrome, but severe cardiac failure could result in anasarca.
Ref: http://www.kumc.edu/instruction/medicine/pathology/ed/keywords/kw_anasarca.html

The nephrotic syndrome is caused by a massive loss of protein in the urine, due to an abnormality of the glomerulus (see page 456, Rubin). The losss of protein, particularly albumin, leads to a decreased oncotic pressure of plasma, and subsequent non-inflammatory edema. The edema is usually generalized, and effusions may also occur.
Ref:
http://www.kumc.edu/instruction/medicine/pathology/ed/keywords/kw_nephroti.html

3.6 Developmental Toxicity. Three prenatal developmental toxicity studies of PFOS have been conducted, two studies in rats and one study in rabbits. In addition, preliminary results are available for developmental toxicity studies in rats and mice. The first study administered four groups of 22 time-mated Sprague-Dawley rats 0, 1, 5, and 10 mg/kg/day PFOS in corn oil by gavage on gestation days (GD) 6-15 (Gortner, 1980). Doses were adjusted according to body weight. Dams were monitored on GD 3-20 for clinical signs of toxicity. Individual body weights were recorded on GD 3, 6, 9, 12, 15, and 20. Animals were sacrificed on GD 20 by cervical dislocation and the ovaries, uteri and contents were examined for the number of corpora lutea, number of viable and non-viable fetuses, number of resorption sites, and number of implantation sites... The most notable sign of developmental toxicity observed in all dose groups consisted of abnormalities of the lens of the eye, which was not seen in controls. The proportion of fetuses with the lens abnormality in one or both lenses was significantly higher in the high dose group. All eye abnormalities appeared to be localized to the area of the embryonal lens nucleus, although a variety of morphological appearances were present within that location. According to the authors, this abnormality appeared to be an arrest in development of the primary lens fibers forming the embryonal lens nucleus. Secondary lens fiber development progressed normally except immediately surrounding the abnormal embryonal nucleus. Under the conditions of the study, a LOAEL for developmental toxicity of 1 mg/kg/day was indicated; a developmental NOAEL could not be established.
Ref: November 21, 2002 report:
Hazard Assessment of Perfluorooctane sulfonate (PFOS) and its salts. Organisation for Economic Co-operation and Development. ENV/JM/RD(2002)17/FINAL.
http://www.fluorideaction.org/pesticides/pfos.final.report.nov.2002.pdf

Environmental - Due to length, click here for effects page

Class Action Suit - Due to length, click here

 
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