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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
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