DEQ-CFW_00002174

CS Risk Assessment
Basic Information
The chemical name for C8 is Perfluorooctanoic acid (PFOA). It has a CAS number of
335-67-1 and a molecular formula of C8HF1502.One of its salts, ammonium
perfluorooctanoate (APFO; C8F15O2NH4; CAS No.3825-26-1) is the compound that is the
most widely used in industry and most of the animal toxicology studies have been done
with this compound. Once absorbed in the body, APFO disassociates to the PFOA anion.
C8 is a completely fluorinated organic acid, meaning that fluorine atoms completely
replace the hydrogen atoms that are typically attached to organic hydrocarbon molecules.
The typical structure has a linear chain of 8 carbon atoms.
C8 is one of many perfluorinated compounds, in the group of chemicals: the
perfluorocarboxylates or known more simply as perfluorochemicals (PFCs). The PFCs
are inherently stable, nonreactive, and resistant to degradation, due to the very high
strength of the carbon -fluorine bond.
Perfluorooctyl sulfonate (PFOS) is another chemical in the PFCs that has received a lot of
attention. This chemical was discovered to be widespread in the blood of the general
population in the late 1990s.
Background
Production of PFCs began in 1947 using an electrochemical fluorination process. Early
uses of the PFCs were based on the chemical's stability, surface -tension lowering
properties, and ability to form stable foams. Some of the uses included fire -fighting
foams, metal plating and cleaning, coating formulations, and polyurethane production.
C8 was produced in several States from 1947 on, with its major use as a processing agent
in the making of products that resist heat, oil, stains, grease, and water. Some common
uses included the production of nonstick cookware, stain -resistant repellants, such as
Scotch -Gard, surfactants, fire retardants, and fire -fighting foams.
C8 was produced by 3M at its Cottage Grove plant in Minnesota from the late 1940s until
2002, by DuPont near Parkersburg, West Virginia also from the late 1940s until 2003,
and is still being made by DuPont near Fayetteville, North Carolina. The North Carolina
facility is the only plant in the U.S. currently manufacturing C8.
In 2001, a class action lawsuit was filed by Ohio and West Virginia residents whose
drinking water was contaminated with C8. Later in that year, the West Virginia
Department of Environmental Protection and DuPont signed a consent order concerning
the presence of C8 in the Lubeck, WV public water supply which is near the DuPont
facility near Parkersburg, WV. The consent order established two scientific teams that
were tasked with 1) determining the extent and concentration of C8 in both groundwater
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and surface water and 2) investigating the toxicity of C8 and developing provisional risk
factors and health protective screening levels.
In March, 2002 EPA Regions 3 and 5 signed a consent order with DuPont requiring the
provision of alternative water to any resident of West Virginia or Ohio with C8 in
drinking water at levels above 14 ppb. The 14 ppb was an interim value that was in effect
until the water screening level was established under the consent order described in the
above paragraph. The 14 ppb was taken from a report by Environ Corp. (a consulting
firm hired by DuPont).
In December 2004, EPA signed a memorandum of understanding (MOU) with 3M and
Dyneon LLC for monitoring in the vicinity of a fluoropolymer manufacturing facility in
Dacatur, Alabama. In November 2005, EPA signed a similar MOU concerning
monitoring at its plant in Parkersburg, WV. In 2005, the class action lawsuit was settled,
with DuPont agreeing to pay $107 million and agreeing to provide a state-of—the-art
water treatment system designed to reduce the level of C8 in the water supply and to
provide medical monitoring.
In 2003, the Environmental Working Group (EWG) petitioned the EPA to investigate
evidence that DuPont violated TSCA 8(e) that requires immediate reporting of findings
that show a "substantial risk of injury to health or the environment." The EWG had
discovered studies that it said had been withheld by DuPont for decades regarding
developmental effects of C8 in laboratory animals.
In December 2005, DuPont agreed to pay $10.25 million in civil fines and fund $6.25
million in research projects to settle allegations that it failed to report environmental
contamination and high levels of C8 found in blood samples from residents near its
Parkersburg, WA plant, under TSCA and RCRA. The EPA said that this was the largest
administrative civil fine ever obtained by EPA under any federal environmental statute.
One of the research projects ($5 million) that DuPont is funding is designed to investigate
the potential of 9 of DuPont's PFCs to breakdown to form C8. The second project will
foster science laboratory curriculum changes to reduce risks posed by chemicals in
schools ($1.25 million).
On January 25, 2006, EPA announced a global stewardship program on C8 and related
chemicals. Eight U.S. companies were asked to commit to reduce C8 and related
chemicals from facility emissions and product content by 95% no later than 2010, and to
work toward eliminating C8 and related chemical content from emissions and product
content no later than 2015. DuPont and several other chemical companies have agreed to
participate in the program.
U.S. EPA Risk Assessment
In January, 2005, the EPA's Office of Pollution Prevention and Toxics (OPPT) issued its
"Draft Risk Assessment of the Potential Human Health Effects Associated with Exposure
to Perfluorooctanoic Acid and its Salts."
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Markin of Exposure
The risk assessment used a margin of exposure approach to describe the potential for
human health effects associated with C8. The MOE was calculated as the ratio of the
NOAEL or LOAEL from a specific endpoint to the estimated human exposure level. The
MOE does not provide an estimate of population risk, but describes the relative
"distance" between the exposure level and the NOAEL and LOAEL.
In this risk assessment, since there was no information available on sources or pathways
of human exposure, but there was information available on serum levels of C8 from
many human biomonitoring studies and from many of the animal toxicology studies,
internal doses from animal and human studies were compared, instead of the traditional
approach which uses external exposure estimates.
A variety of endpoints from animal toxicology studies were used to calculate MOEs. The
endpoints consisted of different species, gender, and life stages. For adults, 2 sets of
MOEs were calculated as follows:
• Based on a cynomolgus monkey study based on increased liver weight and
possible mortality, using the geometric mean for the human serum level =
16,739 (8,191 for the 90th percentile).
• Based on rat study based on reductions in body weight; for males = 9,158
(4,481 for the 90t percentile); for females = 398 (195 for the 90th percentile).
For developmental effects, MOEs were calculated from a 2-generation reproductive
toxicity study in rats, as follows:
• For the prenatal period, for the pregnant human female; since information on the
serum levels of C8 were not available for this study, calculated an MOE based on
the maximum concentration in serum, C. = 3,095 (1,548 for the 90th percentile);
an MOE based on the Area under Concentration curve in plasma (AUC) = 823
(412 for the 90th percentile).
For the postweaning period, MOEs were calculated for several endpoints including
reductions in body weight, mortality, and delayed sexual maturation.
• Based on the geometric mean for children, ranges from 10,484 — 78,546 (6,044 —
45,279 for the 90th percentile).
Carcinogenicity
The risk assessment examined the mode of action and summary of weight of evidence of
the carcinogenicity for C8. All of the epidemiologic data on C8 were occupational
studies, most of which were routine biomonitoring efforts conducted by 3M. With the
exception of one study, all of the studies were cross -sectional and mostly analyzed males.
The only significantly increased cancer incidence found in these studies was an increase
in prostate cancer for workers in the Chemical Division at 3M in Cottage Grove, MN.
However, an update of this study found no significantly elevated cancer rates.
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There are 2 dietary carcinogenicity studies on C8 in rats. In the first study, 50 male and
50 female Sprague-Dawley rats were fed diets containing 1.3 and 14.2 mg/kg-day (males)
or 1.6 and 16.1 mg/kg-day (females) for 2 years. There was a significant increase in the
incidence of testicular (Leydig) cell adenomas in the high dose males and a significant
increase in the incidence of mammary fibroadenomas in both groups of females.
However, the investigators did not consider mammary fibroadenomas to be treatment
related on the basis of the historical control incidence.
In the fd study, male Sprague Dawley rats were exposed to 300 ppm for 2 years. There
was a significant increase in the incidence of Leydig cell adenomas in the treated rats as
compared to controls and the treated rats had an increase in the incidence of liver
adenomas and pancreatic acinar cell tumors.
EPA concluded that 2 carcinogenicity studies have shown that C8 induced liver
adenomas, Leydig cell adenomas, and pancreatic acinar cell tumors in male Sprague-
Dawley rats. The evidence for mammary fibroadenomas in the female rats was
considered to be equivocal since the incidences were comparable to some background
incidences.
Mode of Action and Weight of Evidence for Carcino enicity
C8 has not been shown to be genotoxic. Strong evidence exists that the liver toxicity and
liver adenomas seen in rats following exposure to C8 result from peroxisome proliferator-
activated receptor (PPAR)a-agonist mode of action. This mode of action involves 4 steps
(see Figure 1):
1. Activation of PPARa (which regulates the transcription of genes involved in
peroxisome proliferation, cell cycle control, apoptosis, and lipid metabolism).
2. This leads to an increase in cell proliferation and a decrease in apoptosis.
3. This further leads to preneoplastic cells and further clonal expansion.
4. Formation of liver tumors.
Only PPARa activation is highly specific for this mode of action. There are also several
associative events that are markers of PPARa agonism but are not directly involved in the
etiology of liver tumors: Peroxisome proliferation and peroxisomal gene expression.
OPPTS issued guidance in 2003 to help establish that a chemical is exhibiting liver
toxicity and tumors via a PPARa agonist mode of action: in vitro evidence of PPARa
agonism, in vivo evidence of an increase in the number and size of peroxisomes, increase
in the activity of acyl CoA oxidase, and hepatic cell proliferation.
There is sufficient evidence to demonstrate the key events for a PPARa agonist mode of
action following exposure to C8 in rats.
Several scientific groups have examined the role of PPARa-induced rodent liver tumors
and its relevance for human carcinogenesis. In 1995, a workgroup convened by IARC
concluded that the mode of action induced in rodents by PPARa agonists is unlikely to be
operative in humans. A workshop held by the International Life Sciences Institute (ILSI)
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Health and Environmental Sciences Institute concluded that although it appeared unlikely
that PPARa agonists could induce liver tumorigenesis in humans, the possibility could
not be ruled out. An analysis by Klaunig et al. (2003) concluded that:
1. The weight of evidence in linking PPARa to the mode of carcinogenic action of
C8 is high for the liver,
2. The PPARa mode of action is plausible in humans since the PPARa is present
in humans and human livers possess PPARa at sufficient levels to mediate the
hypolipidaemic response to therapeutic fibrate drugs, many of which are
PPARa agonists,
3. The weight of evidence, however suggests that this mode of action is unlikely
to occur in humans based on quantitative differences in several of the key
factors, such as human livers have been found to have 10-fold less mRNA for
PPARa compared with rodents.
In 2004, the majority of a FIFRA Science Advisory Panel agreed that that are relevant
data indicating that humans are less sensitive than rodents to the hepatic effects of
PPARa agonists and stated that when liver tumors are established in long term studies in
rats and mice and:
1. the data are sufficient to establish that the liver tumors are a result of PPARa
agonist mode of action, and
2. other potential modes of action have been evaluated and found not to be
operative,
Then the evidence for liver tumor formation in rodents should not be used to characterize
potential human liver cancer risk.
On May 30, 2006, the SAB issued their report reviewing EPA's risk assessment of C8.
One of the issues they examined was the weight of evidence of carcinogenicity and the
adequacy of the data for PPARa agonist induced rodent liver toxicity. The SAB
concluded:
• Evidence to date was consistent with an interpretation that liver tumor induction
likely results from a PPARa-agonist mode of action. However, the panel members
did not agree on whether PPARa is the sole mode of action for rodent liver tumor
induction and toxicity. Most panel members felt, based on current evidence, that it
is possible that PPARc t agonism may not be the sole mode of action for C8, that
not all steps in the pathway of PPARa activation -induced liver tumors have been
demonstrated, that other hepatoproliferative lesions require clarification, and that
extrapolation of the mode of action across the age range in humans is not
supported.
Regarding the weight of evidence of carcinogenicity, the risk assessment reached the
conclusion that C8 exhibited "suggestive" evidence of carcinogenicity but not sufficient
to assess the carcinogenic potential of C8. This was based on the following:
1. A PPARa-agonist mode of action for liver tumors in rodents that was not
considered relevant to humans because of their decreased sensitivity to PPARa-
agonism when compared to rodents,
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2. The absence of hepatic cell proliferation in a 6-month study of C8 in
cynomolgous monkeys, the species considered closest in physiology to humans,
3. The absence of a strong association between C8 exposure and tumors in human
studies,
4. The belief that the Leydig cell tumors and pancreatic acinar cell tumors
produced by C8 in rats were probably not relevant to humans based on lower
levels of certain hormones in humans and differences in quantitative
toxicodynamics between rats and humans,
5. The belief that the mammary fibroadenomas reported in female rats are
equivocal based on their comparable rates of occurrence relative to a historical
control group.
Most panel members of the SAB concluded that the experimental weight of evidence
with respect to the carcinogenicity of C8 was stronger than proposed in the draft
document and suggested that C8 should be considered "likely to be carcinogenic in
humans." This was based on the following:
• While human data are ambiguous, 2 separate feeding studies in rats have
shown cancer in several sites,
• Uncertainties still exist as to whether PPARa agonism is the sole mode
of action for C8 effects on the liver,
• It was inappropriate to exclude mammary tumors in the document based
on comparisons to historical control levels for other laboratories, since
the most appropriate control group is a concurrent control group. Using
that comparison, there was an increase in mammary gland tumors,
• Insufficient data are available to determine the mode of action for the
Leydig cell tumors, pancreatic acinar cell tumors, and mammary gland
tumors. In the absence of a defined mode of action, they must be
presumed relevant to humans.
These panel members were not willing to state an associated probability for C8-induced
carcinogenicity, but most panel members believed that risk assessments for each of the
C8-induced tumors are appropriate at the current time.
A few panel members disagreed and stated that currently available evidence does not
exceed the "suggestive" evidence of carcinogenicity descriptor, based on the belief that
PPARa does serve as the sole mode of action for C8-induced rodent liver tumors and that
mammary tumors were not demonstrated in animals compared to historical controls.
West Virginia Risk Assessment
In August 2002, the WV Department of Environmental Protection issued its "Final
Ammonium Perfluorooctanoate (C8) Assessment of Toxicity Team (CATT) Report".
This report was the result of the consent order between the State of WV and DuPont that
said that a scientific team was to 1) determine risk -based human health protective
screening levels of C8 in air, water, and soil; 2) provide health risk information to the
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public, and 3) determine an ecological health protective screening level for C8 in surface
water.
Noncancer Risk Assessment
The CATT report developed screening levels for C8 in air, water, and soil. The panel
agreed that the human studies were not adequate to be used for quantitative dose -
response determinations. They reviewed the relevant animal studies and determined that
the primary target organ for C8 is the liver. They selected a 2-generation rat study as the
critical study and selected the following:
Key study
Species,
NOAEL
LOAEL
BNWL
Critical
OF
sex
effect
York et al.
Rat, male
None
1
0.42
Liver
100
2002
The uncertainty factor of 100 was selected based on an individual factor of 10 for human
variability and another factor of 10 for interspecies variability.
The RfD = 0.42/100 = 0.0042 mg/kg-day. The value was rounded to 0.004 mg/kg-day.
Cancer Risk Assessment
Liver tumors: The majority of the panel members agreed that peroxisome proliferation is
the mode of action for the liver tumors. Some of the panel members felt that the use of
the liver tumor response data for human health risk assessment cannot be totally
discounted, while others felt that the rodent liver tumors are not relevant at all to humans.
Leydig cell tumors: The panel agreed that these tumors were likely to be caused by a non-
genotoxic mechanism. They also agreed that the Leydig cell tumors are a known tumor
type for other peroxisome proliferators; however they could not reach a conclusion as to
whether this tumor type is relevant to humans.
Pancreatic tumors: The panel agreed that the evidence was not sufficient to demonstrate
the mode of action for pancreatic tumors, but enhanced cell proliferation (hyperplasia)
was likely to be involved. The mode of action appears to be nongenotoxic.
Mammary fibroadenomas: The panel agreed that the data were not adequate to
demonstrate a mode of action. Several panelists were not convinced the data
demonstrated a real carcinogenic effect.
Dose -Response Assessment — The panel members agreed to recommend a dose -response
approach for each tumor type.
Liver tumors: MOE approach. Since the MOE analysis often uses the benchmark
response for a precursor as the basis for deriving a point of departure, the panel judged
the Rf) for liver effects as sufficiently protective for potential liver carcinogenicity.
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Leydig cell tumors: Benchmark dose modeling was conducted. The point of departure for
Leydig cell tumors was chosen by the panel from the BMD modeling output. A BMDL of
0.32 mg/kg-day was selected as the most appropriate basis for deriving the assessment.
An oral cancer slope factor was calculated as follows:
Slope factor = risk/dose = 0.1/0.32 = 0.31 per mg/kg-day.
Risk was expressed as 0.1 because the BMDL is the point that represents a 10% increase
in tumor incidence in accordance with EPA guidance.
ScreeningLevels
evels
The panel agreed that the oral RM for liver toxicity would be the basis for determining
the water and soil screening levels for the following reasons:
• High confidence in the RfD
• The RM would be protective against the quantitatively less sensitive and
questionably relevant peroxisome proliferation -related liver cancer
• Low confidence in the Leydig tumor analysis and questionable relevance to
humans
• Limitations in study design, data quality, and data interpretation made it
difficult to determine whether the increased incidence of pancreatic tumors or
mammary tumors were related to C8 treatment and did not allow for the
modeling of a point of departure to be used for quantitative risk assessment.
The following equations were used to derive screening levels (from EPA Region 9
guidance on deriving risk based concentrations):
Air Screening Level = µg/m3 = THQ x Rf )i x BW x AT x 1000
EF x ED x air IR
With RfDi (mg/kg-day) = RfC x 20 m3/day (IR)
70 kg (BW)
Soil Screening Level = mg/kg = THQ x AT x BW
EF x ED x [soil IR/RID x 10-6 + SA x AF x ABS/RM x 10-6]
Water Screening Level = µg/L = THQ x AT x BW x 1000
EF x ED x [water HUM]
Where:
THQ = Target hazard Quotient, assumed to be 1
Rf )i = The RfC expressed in terms of dose, mg/kg-day
The oral reference dose estimated by the panel, 0.004 mg/kg-day
RfC = The inhalation RfC estimated by the panel
BW = Body weight, assumed to be 70 kg for adults and 15 kg for children
AT = Averaging time, 10950 days, the exposure duration expressed in days
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EF = Exposure frequency, 350 days/year, the average number of years people are
exposed
ED = Exposure duration, 30 years, the average number of years people are
exposed
IR = Inhalation rate for air screening levels, 20 m3/day; Ingestion rate for soil and,
Water Screening levels, 200 mg/day soil ingested based on child exposure and, 2 L/day
ingested based on adult exposure
SA = Surface area of exposed skin, 2800 cm2/day
AF = Adherence factor, 0.2 mg/cm2, the amount of soil that adheres to skin
ABS = Skin absorption factor, specific factor not available for C8, assumed to be
0.1 for semi -volatile chemical per EPA guidance.
The following screening levels were calculated:
Air: 0.1— 6.0 µ9/m3
Soil: 244 mg/kg residential soil, rounded to 240 mg/kg
Water: 146 µg/L, rounded to 150 µg/L.
Minnesota Number
The state of Minnesota has not carried out a risk assessment for C8. However, in 2002
they calculated a health based value (HBV) for C8 and residential and industrial soil
reference values.
MN calculated a HBV as follows:
Study: Thomford et al., 2001 (26 week study in monkeys)
Critical endpoint: Liver effects
LOAEL = 3 mg/kg-day
OF = 3000 (3 for interspecies variability, 10 for intraspecies variability, and 10 for
subchronic to chronic, and 10 for LOAEL to NOAEL).
RfD = 0.001 mg/kg-day
Relative source contribution = 20%
HBV = RfD (m /g_kg-day) (RSC) (1000 M/g_mg)
Intake rate (2 L/day/70 kg)
_ (0.001 m /g_kg-d")(0.2)(1000 µ�Jm�) = 7 µg/L
0.029 L/kg/day
MN calculated the following soil reference values (SRV) for C8:
Residential SRV = 30 mg/kg
Industrial SRV = 200 mg/kg
(The calculations were not provided for these values)
Ohio Number
The state of Ohio has not carried out a risk assessment for C8. However, they have posted
a letter on their website stating that they are relying on the U.S. EPA to study C8 and
cited the West Virginia Preliminary Action Level of 150 ppb. They said that all the
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detections of C8 in public water supplies are below this level and that they will take
whatever action is necessary to be certain that Ohio is not distributing drinking water
with levels of C8 above any level that EPA establishes.
New Jersey Number
The state of New Jersey has adopted an "Interim Guidance Criteria" for C8. In situations
where no specific criteria exists for a synthetic organic chemical, the New Jersey Ground
Water Quality Standards specify the establishment of an interim guidance criteria of 5
ppb for compounds identified as having "evidence of carcinogenicity." Since C8 has been
shown to demonstrate evidence of carcinogenicity in rats, New Jersey set their interim
guidance at 5 ppb.
ATSDR Health Consultation
In February, 2005, ATSDR published a health consultation for C8 and PFOS at the 3M
Cottage Grove facility in Minnesota.
ATSDR summarized the same health studies that were reviewed in the EPA and West
Virginia risk assessments. They cited the Minnesota HBV and SRVs (see above).
ATSDR also summarized the available environmental data, stating that PFOA does not
bioconcentrate through the food chain, while PFOS does. Bald eagles from the Midwest
showed the highest levels of PFOS in plasma (up to 2,570 ng/mL) and mink from the
Midwest showed the highest levels in tissue (in liver, up to 3,680 ng/g). Concentrations
of C8 in wildlife samples are typically approximately 10 times lower and are much less
widely distributed.
This report did not reach any conclusions, "The potential impacts on public health from
perfluorchemical releases at the 3M Cottage Grove facility cannot be fully assessed at
this time, because there are not sufficient environmental data available regarding PFC
impacts from the facility in soil, groundwater, surface water, sediments, and biota. At this
time perfluorochemical releases from the site represent an indeterminate public health
hazard."
C8 and Related Compounds in Blood
Mean C8 Levels in the General Population:
Studies on 3 separate age groups across the U.S. — mean C8 levels = approximately 4-5
ppb C8 in serum (EPA, 2005).
C8 in Workers:
3M biomonitoring in Decatur, Alabama plant, mean C8 levels, 1997 =1,400 ppb; 1998 =
1,540 ppb; 2000 =1,780 ppb; 2002 =1,497 ppb (EPA, 2005).
3M biomonitoring in Cottage Grove, MN plant, mean C8 levels, 1995 = 6,800 ppb; 1997
= 6,400 ppb; 2000 = 4,510 ppb; 2002 = 4,300 ppb (EPA, 2005).
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DuPont biomonitoring in its Washington Works, WV plant, mean C8 levels, 1989-90 =
1,960 ppb; 1995 =1,560 ppb; 2000 =1,530 ppb (EPA, 2005).
DuPont biomonitoring in its Fayetteville, NC plant, mean C8 levels, 2002 =11 ppb;
2003 = 217 ppb (DuPont Biennial Report for the Manufacture of APFO letter, October
26, 2004).
Mean PFOS Levels in the General Population:
Mean serum levels of PFOS in the nonoccupational general population in the U.S. = 30-
40 ppb in serum (Olsen et al., 2005).
PFOS in Workers:
Mean serum levels of PFOS in workers have averaged between 500 and 2,000 ppb in
serum (Olsen et al., 2005).
C8 Levels in the Environment
Concentrations in water
U.S.
Analyzed 16 Great Lakes water samples for C8: Concentrations ranged from 27-50 ng/L
(Boulanger et al., 2004).
Monitored for C8 in surface waters in the Great Lakes, and lakes in Michigan,
Wisconsin, and Minnesota. Found C8 in all samples; levels in remote areas ranged from
0.14 to 0.66 ng/L and levels in urban surface waters ranged from 0.45 to 19 ng/L. The
authors concluded that the primary source of the C8 found in Lake Michigan was most
likely from wastewater treatment effluents, and was not from the air (Simcik and
Dorweiler, 2005).
Outside the U.S.
Japan: Most major rivers and several lakes in Japan have been sampled. Most C8
concentrations were as low as 0.1 ng/L in remote areas and about 2-10 ng/L in urban
areas (Prevedouros et al., in press).
Japan: Analyzed rivers and lakes in Japan with C8 concentrations ranging from a mean of
0.97 — 21.5 ng/L. C8 in drinking water in Osaka City measured at 40 ng/L, significantly
higher than in other cities measured (Saito et al., 2004).
The Orient: Analyzed for C8 in coastal seawaters of Hong Kong, The Pearl River Delta,
and Korea, with concentrations of 0.73-5.5, 0.24-16, and 0.24-320 pg/mL, respectively
(So et al., 2004).
Concentrations in sediment
U.S. and other countries: Sediment samples from a small U.S. city, the Netherlands,
several Scandanavian countries, the San Francisco Bay, and the Niagara River reported
C8 levels of 24 pg/g to 18 ng/g. Samples with concentrations over 1 ng/g were atypical
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with the majority of the reported concentrations in the hundreds pg/g range (Prevedouros
et al., in press).
Concentrations in air from precipitation and in snow
U.S.
C8 was detected as high as 50 ng/L, but generally less than 10 ng/L, in precipitation
samples from 3 different U.S. sites in 1998 (Prevedouros et al., in press).
Outside the U.S.
Finland and Sweden: C8 found in precipitation with a concentration range of 8-17 ng/L
(Prevedouros et al., in press).
High Arctic: C8 found in snow and ice caps at 2-3 ng/L (Prevedouros et al., in press).
Concentrations in wildlife
U.S.
C8 found in loggerhead turtles (mean conc. = 3.20 ng/mL) and Kemp's ridley turtles
(mean conc. = 3.57 ng/mL) in inshore waters of Core Sound, North Carolina and offshore
waters of South Carolina, Georgia, and Florida (Keller et al., 2005).
C8 detected in some samples (PFOS found in all samples) of the livers of mink and river
otters collected across the U.S., with a maximum concentration of 27 ng/g (Kannan et al.,
2002a).
Outside the U.S.
South America: C8 found in bile of fish (mullets) in Colombia at concentrations ranging
from 1.27 — 713 ng/mL (Olivero-Verbel et al., 2005).
Japan and Korea: C8 detected in 5-10% samples of livers of birds, with a maximum
concentration of 21 ng/g (Kannan et al., 2002b).
Baltic and Mediterranean Seas and coast: C8 detected sporadically (PFOS detected in all
samples) in liver and blood of fish, dolphins, seals, whales, and eagles. Highest
concentration of 95 g/g reported (Kannan et al., 2002c).
Concentrations in house dust
Canada: C8 found in house dust in Ottawa (Kubwabo et al., 2005).
Japan: C8 detected in vacuum cleaner dust in all homes sampled at 69 — 3,700 ng/g
(Moriwaki et al., 2003).
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Figure 1
Key Events in the Mode of Action for PPARa Agonist Induced Rodent Liver
Tumors
PPARa Agonist ->
Causative Events
Activation of PPARa Associative Events —
I Expression of Peroxisomal genes
Increase in Peroxisomes (number
and size)
Cell Proliferation
Decreased Apoptosis
y
Preneoplastic foci
Clonal expansion
Liver tumors
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