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Review Paper
Human detoxification of perfluorinated compounds
S.J. Genuis
a,
*, D. Birkholz
a
, M. Ralitsch
b
, N. Thibault
b
a
University of Alberta, Canada
b
A.L.S. Laboratory Group
article info
Article history:
Received 24 August 2009
Received in revised form
10 February 2010
Accepted 2 March 2010
Available online 19 June 2010
Keywords:
Bile acid sequestrants
Cholestyramine
Detoxification
Enterohepatic circulation
Perfluorinated compounds
Public health
Saponin compounds
Sauna therapy
Toxicology
Zeolites
summary
There has been no proven method thus far to accelerate the clearance of potentially toxic
perfluorinated compounds (PFCs) in humans. PFCs are a family of commonly used synthetic
compounds with many applications, including repelling oil and stains on furniture, clothing,
carpetsand food packaging, as wellas in the manufacturing of polytetrafluoroethylene– a non-
stick surfacingoften used in cookware (e.g. Teflon(r)). Some PFCs remain persistent within the
environment dueto their inherent chemical stability, and are very slowly eliminated from the
human body due, in part, to enterohepatic recirculation. Exposure to PFCs is widespread and
some subpopulations, living in proximity to or working in fluorochemical manufacturing
plants, arehighly contaminated. PFC bioaccumulation has becomean increasing public health
concern as emerging evidence suggests reproductive toxicity, neurotoxicity and hepatotox-
icity, andsome PFCs are consideredto be likely human carcinogens.A case history ispresented
where an individual with high concentrations of PFCs in serum provided: (1) sweat samples
after use of a sauna; and (2) stool samples before and after oral administration of each of two
bile acid sequestrants – cholestyramine (CSM) and saponin compounds (SPCs). Stool samples
before andafter use of a cation-exchangezeolite compoundwere also examined.PFCs found in
serum were not detected in substantial quantities in sweat or in stool prior to treatment.
Minimal amounts of perfluorooctanoicacid, but no other PFCs, were detectedin stool after SPC
use; minimal amounts of perfluorooctanesulfonate, but no other PFCs, were detected in stool
after zeoliteuse. All PFC congeners foundin serum were detected in stoolafter CSM use. Serum
levels of all PFCs subsequently declined after regular use of CSM. Further study is required but
this report suggests that CSM therapy may facilitate gastrointestinalelimination of some PFCs
from the human body.
ª2010 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
Introduction
Over the last two decades, there has been increasing discussion
in the scientific and public health literature about adverse effects
of bioaccumulative toxicant exposure.
1,2
A family of chemical
agents which has garnered increasing attention in toxicological
and environmental literature is the perfluorinated compounds
(PFCs), both parent compounds and their metabolites. Concern
has arisen because the ultimate breakdown products of per-
fluorinated parent chemicals are perfluorinated acids (PFAs),
some of which are persistent in the environment and can accu-
mulate in the human body and in food chains. Emerging
evidence in animal research and in preliminary human
epidemiology studies suggests the potential for toxicity with
*Corresponding author. 2935-66 Street, Edmonton, Alberta T6K 4C1, Canada. Tel.: þ1 780 450 3504; fax: þ1 780 490 1803.
E-mail address: sgenuis@ualberta.ca (S.J. Genuis).
available at www.sciencedirect.com
Public Health
journal homepage: www.elsevier.com/puhe
public health 124 (2010) 367–375
0033-3506/$ – see front matter ª2010 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.puhe.2010.03.002
Author's personal copy
exposure and accrual of PFAs. The recently released ‘Fourth
National Report on Human Exposure to Environmental Chem-
icals’ from the Centers for Disease Control and Prevention
confirms that most Americans have bioaccumulated per-
fluorochemicals in their bodies.
1
In this paper, a brief overview of
the current understanding of the significance of PFC toxicant
exposure is followed by a discussion of PFC elimination and
a case report involving human PFC excretion after therapeutic
intervention.
Perfluorinated compounds
PFCs are a family of man-made compounds which have been
manufactured over the last 60 years and have been used in
various commercial applications. Structurally, these chem-
ical agents consist of a linear or branched carbon backbone
that is entirely substituted by strong bonds to fluorine atoms.
The fluorine component of PFCs provides extremely low
surface tension and accounts for their unique hydrophobic
(water repelling) and lipophobic (lipid repelling) nature.
3
These compounds differ markedly from most other chem-
ical surfactants in that they are very stable, non-reactive and
effective at low concentrations. With such unique properties,
selected PFCs have been used to make commercial products
that are resistant to both water and oil, and can also with-
stand the extremes of temperature, pH and oxidizing
conditions.
PFCs have primarily been used in domestic and industrial
contexts specifically for their repellant properties. With the
propensity to deter stains and prevent adhesion, these
compounds have been utilized in clothing, cookware, furniture,
carpeting and with various other applications to prevent stains
and sticking. Animalstudies suggest that PFCsare generally well
absorbed by oral intake and inhalation. As a result, in domestic
and commercial settings, many people have regular exposure to
PFCs through inhalation, ingestion and, perhaps, dermal
contact. In addition, accidental spills of PFCs have recently
occurred where individuals have beenexposed to elevated levels
of theseagents throughavenues suchas the water supply.
4
With
increasing presence of these agents in the environment and
bioaccumulation in some individuals, research to understand
PFC toxicokinetics and modes of action is currently underway.
4,5
Toxicokinetics
There is significant chemical variation within the family of PFCs
that accounts for marked differences in behaviour and potential
toxicity between specific perfluorinated molecules. Some
compounds such as perfluorobutyrate, for example, appear to
be readily excreted with a low potential for bioaccumulation.
6
Other PFCs, however, are persistent, non-biodegradable and
bioaccumulative within the human body.
1,3,7
The three most
widely known PFCs – perfluorooctanoic acid (PFOA), per-
fluorooctanesulfonate (PFOS) and perfluorohexansulfonate
(PFHxS)– have significant potentialfor endogenous accrualafter
exposure. Although initially thought to be biologically inactive,
the persistence of these agents within the human organism has
generatedincreasing concern about the potential for some PFCs
to disrupt physiological processes.
PFCs appear to be primarily excreted by the liverand possibly
the kidney. Although they often enter the intestine as a compo-
nent of bile, it appears that most PFCs may be re-absorbed and
returned to the liver through the enterohepatic circulation
3
where the cycle of biliary excretion and re-absorption recom-
mences repeatedly.
8
In addition, there is increasing evidence in
the literature that persistence in the body may also result from
impaired renal excretion of some PFCs due to renal tubular re-
absorption mediated through organic anion transporters.
9–12
Although there has been discussion of the impact of pH
changeson renal re-absorption of some toxicants, determinants
of renal excretion are not completely understood and there is no
known clinical intervention at this juncture to preclude PFC re-
absorption in the kidney.
In review, certain precursor PFCs can be metabolized in the
body to PFAs, these acids are not further metabolized and are
eliminated at a slow rate, they tend to accrue in the organism,
and they distribute mainly to the serum, liver and kidney,
13
with hepatic levels reaching values much higher than serum
concentrations in some animals.
14,15
It is uncertain, however,
what the relative concentrations for various PFAs are between
blood and various tissues in humans as there appears to be
variance of tissue distribution between species and between
different PFA compounds.
13,16
After PFC parent compounds
are metabolized to PFAs, however, it appears that these
persistent compounds in serum are highly bound to protein
and are repeatedly shunted to the liver and kidney en route to
attempted clearance and subsequent re-absorption, resulting
in prolonged circulating levels of some PFAs after exposure
has occurred.
Individual chain-length homologues within families of PFCs
have a considerable range of elimination rates and half-lives
but, as discussed, some PFAs tend to be very persistent in the
human body. The median human serum half-lives for common
PFAs are: PFHxS, 8.8 years (range 2.8–27); PFOS, 5.4 years (range
2.4–21.7); and PFOA, 3.8 years (range 1.5–9.1).
17
Between indi-
viduals, there may be variation in biological breakdown of
precursors and elimination of PFAs due to differences in indi-
vidual biochemistry and physiology based on genomic and
metabolic variation. A gender difference in elimination of PFCs
in humans has not been observed thus far.
7
Due to the bio-
accumulative nature of some PFCs, there is increasing concern
about adverse health sequelae; an apprehension which has
recently spawned much international attention and increasing
research.
Potential toxicity
Most PFC toxicity work thus far has been done on animals. In
animal research, common PFCs such as PFOA and PFOS appear
to be potentially carcinogenic,
18
induce functional alteration in
cellular organelles,
19–21
and cause neurotoxicity and hepato-
toxicity.
18,22,23
The literature also confirms significant PFC
adverse effects on immune system function,
24
cell membrane
potential,
25
neuroendocrine function,
26
and gestational and
developmental processes.
27,28
In summary, animal research
evidence to date confirms that some PFCs have potential for
hepatotoxicity, developmental toxicity, immunotoxicity,
hormonal disruption, and genomic and biochemical impact.
3
Although the aforementioned effects often occur at higher
public health 124 (2010) 367–375368
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doses than those which most humans are exposedto, potential
human thresholds for harm are currently unknown. With
increasing recognition of verified toxicity in short-term animal
studies, researchon the short- and long-term impact of PFAs on
human health has increased.
In-vitro studies on cells derived from humans have demon-
strated that some PFCs may be genotoxic,
29
somehave impact on
intracellular organelles,
30
and some demonstrate oestrogenic
effects.
31
In population studies, there is recent evidence that
human fecundity is affected by some PFCs, with the suggestion
that some of these compounds may act as hormone disruptors.
32
In addition, a large Danish cohort study recently demonstrated
that fetal birth weight is impaired by background exposure to
PFOA.
33
Although findings are not yet conclusive, the Science
Advisory Board of the Environmental Protection Agency from
the US Government has found that there is sufficient evidence
to consider PFOA to be a likely carcinogen in humans.
34
In
addition, there has been vigilant observation of a large pop-
ulation of people in West Virginia (approximately 100,000)
who sustained substantial exposure and bioaccumulation of
PFCs due to drinking water contamination at an industrial
site. Preliminary findings in studies on exposed individuals
suggest a number of adverse sequelae including altered
hepatic function, immune function, thyroid function and
cholesterol physiology.
5
Therapeutic interventions
There is very limited information in the literature about
interventions to facilitate elimination of PFCs.
35
One report in
the scientific literature assessed the use of a bile acid
sequestrant (BAS) cholestyramine (CSM) to facilitate excretion
of some PFCs in rats: CSM enhanced PFOS and PFOA excretion
by approximately 9.5–10 fold.
36
The researchers also found
that levels of retained PFCs in liver and plasma after CSM
treatment were significantly diminished as a result of
enhanced excretion.
36
It has also been noted in some
preliminary unpublished work that intervention with non-
absorbable fats may hasten the removal of PFCs in animals.
Jandacek assessed the 48-h excretion of PFOA in animals 7
days after dosing with Olestra (an agent acting as a lipophilic
sink to impair fat absorption); excretion of PFOA was doubled
in the treated group.
37
Researchers at 3M, a major producer of PFCs, claim to
have investigated the effectiveness of colesevelam HCL
(another BAS noted for its preferred tolerability) in lowering
blood levels of PFOA in cynomolgus monkeys.
38
Under
conditions of a preliminary study, they report that colese-
velam HCL did not appear to be highly effective in dimin-
ishing serum PFOA values, but investigations for PFOS or
PFHxS elimination were not performed. As sulfonate
compounds may bind more strongly than PFOA, it is unclear
if colesevelam HCL might have a more pronounced effect
with PFOS and PFHxS.
To summarize, there is minimal to no research to be found
on successful therapeutic interventions to remove persistent
PFCs from the human body. This paper is the first to report on
therapeutic measures to facilitate human excretion of PFCs in
an individual noted to have high levels of PFCs in serum testing.
Case history
Patient description
A 51-year-old asymptomatic male medical researcher, who
volunteered to be a control participant in an institutional
review board (Health Ethics and Research Board at the
University of Alberta) approved research study on toxicant
bioaccumulation and excretion in chronically ill patients, was
unexpectedly found to have markedly elevated serum levels
of selected PFCs. Assorted other chemicals were explored in
this study including blood, urine and sweat levels of poly-
brominated diphenyl ethers, phthalates, bisphenol A,
solvents, heavy metals, organochlorine pesticides and poly-
chlorinated biphenyls. No elevated levels of toxicants other
than serum PFCs were found in the blood, sweat or urine of
the volunteer (hereinafter referred to as the ‘patient’).
Upon receiving the results, the patient requested that all
family members who had lived in the same residence be
tested for PFCs. Approval by the University of Alberta Health
Ethics and Research Board was also received for a subsequent
pilot study to test and provide ongoing follow-up for the
patient and his family, and to assess the potential source of
the exposure by retrieving various samples from within their
household. All other individuals living in the same household
were eventually found to have a profile of elevated PFCs,
including one child with a serum PFHxS level of 423 ng/g and
a PFOS level of 108 ng/g [the 95th percentile from the NHANES
study (2003/2004) was 8.3 for PFHxS and 54.6 for PFOS
39
].
Information gathered through personal interviews
revealed that the family lived in Edmonton, Alberta, Canada –
a locale with latitude of 53300N and a climate of long, cold
winters. Their place of residence was a house heated by in-
floor heating, made up of water-filled rubber tubing running
immediately beneath the sub-floor. The in-floor heating was
turned off in the summer months but was used routinely
between September and May each year. On inspection, their
home was found to have poor ventilation and air exchange.
Most of the house, including all the bedrooms, was floored
with carpeting, which had been treated intermittently for
stain and soil repellence since 1989. No apparent occupational
exposure or unusual dietary habits were discovered for the
patient or any members of the household. Samples of dust
and carpet collected from the family’s home eventually
confirmed high levels of PFCs, particularly PFHxS.
Within his clinical medical practice, the first author has
repeatedly found markedly elevated PFC levels (usually PFHxS
and PFOS) in serum samples of residents (unrelated to the
patient in this case report) living in carpeted homes with in-
floor heating, but not in residents of carpeted homes without
in-floor heating systems (including homes with carpets
receiving intermittent Scotchgard treatments). The reasons
for elevated PFC exposure in this patient are the subject of
ongoing investigation, but the preliminary hypothesis (which
received additional support from the findings of noteworthy
PFC levels in the carpets and air in all the carpeted rooms
within his home) was that off-gassing from heated carpets
which had been intermittently treated with Scotchgard (tm)
for carpet stain resistance and protection, released PFCs into
public health 124 (2010) 367–375 369
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the air which were inhaled by the patient and members of his
family. The carpets were completely removed from the home
in January 2009.
There was discussion about the health history of the family, as
the patient’s spouse had sustained two consecutive mid-term
pregnancy losses shortly after moving into this home, whereas
her previous obstetrical and health history had been unremark-
able. With concern about the well-being of his family and wishing
to preclude potential health problems associated with elevated
PFCs, the patient researched the scientific literature extensively
with regards to the potential sequelae associated with PFC bio-
accumulation. As independent emerging evidence found in the
scientific literature demonstrated potential adverse biological
effects,
32,33,40
the participant was eager to consider options to
diminish PFC levels with the objective of minimizing associated
health risks. Over many months, he sought advice and counsel
from individuals involved in environmental health sciences and
toxicological research on possible interventions in order to reduce
the levels of PFCs for him and his family. He also contacted a major
manufacturer of PFCs and, contrary to information from other
sources, was adamantly told that there were absolutely no risks
associated with elevated PFC concentrations in people, in food
webs or in the environment, and was also informed that there was
no known intervention to hasten human excretion of PFCs.
The patient explored and accumulated information
relating to assorted possible therapies that might facilitate
and hasten excretion of bioaccumulative compounds,
including use of BASs,
41–44
pancreatic lipase inhibitors,
8
non-
absorbable lipids,
45–47
sauna depuration,
48–50
serial phle-
botomy (as is used in haemochromatosis) and therapeutic
apheresis. He also sought advice about assorted complemen-
tary and alternative therapies, including the use of herbal
agents such as zeolites
51–53
and saponin compounds (SPCs).
SPCs-originating from soy or the yucca plant are alleged to
have a BAS mechanism of action.
54–57
After consultation with various researchers including
toxicologists and environmental health scientists, the patient
chose to try the BAS CSM for various reasons:
ease of use, ready availability of medication, and absence of
invasive intervention;
long-term CSM has been employed for other indications
(including treatment of elevated lipids) and has an excellent
track record of safety;
CSM is not absorbed into the body, but binds strongly to
selected adverse compounds and is excreted along with the
toxicant. With lack of absorption, CSM is considered by
some clinicians to be less potentially toxic than many over-
the-counter medicaments in common usage;
animal work has confirmed that CSM may facilitate excre-
tion of some PFCs
36
;
the side-effect profile of CSM is very tolerable (although long-
term use of CSM may cause a deficiency of fat-soluble nutri-
ents including vitamins A, D, E and K, and coenzyme Q10,
nutrient supplementation ingested a few hours away from
medication intake can be used to maintain nutrient levels); and
repeated and long-term administration of CSM (more than 3
years) has reportedly been used by some clinicians for
mould- and mycotoxin-exposed ill patients with good
results and without noticeable adverse effects.
58–60
It is important to note that the self-directed treatment plan
using CSM by the individual in this case history was under-
taken of his own volition.
As well as deciding to embark on a trial of treatment with
CSM, the patient decided to explore the potential efficacy of
sauna depuration as a measure to facilitate elimination of his
accumulated PFCs. To determine the potential for success, he
initially decided to use CSM for 1 week and to have post-
treatment stool PFC levels measured. At a later point, he
repeated the same procedure with SPCs and zeolites to
determine if these non-pharmaceutical agents might also
facilitate PFC elimination. The PFC results from each of the
family members and the household contents will be discussed
in subsequent papers after adequate analysis is completed;
this paper provides a case history to report the results of self-
directed CSM use in this individual patient.
Sample collection
Prior to commencing CSM treatment, the patient collected
blood, sweat, urine and stool samples for PFC assessment.
Three independent blood draws were taken in the year prior to
commencing treatment in order to confirm and follow levels
of PFCs. Recognizing that induced perspiration can be an
effective means to excrete some chemical toxicants,
48–50
sweat was collected during three sessions in an infra-red dry
sauna. The patient showered prior to using the sauna and
brushed off the area of skin from the trunk and axillae area
where perspiration was to be collected. A stainless steel
spatula was used to collect the sweat, and the body fluid was
placed into a glass jar and delivered to the laboratory for
assessment. The urine and faecal samples were collected
directly into glass collection jars provided by the laboratory.
In June 2008, the patient commenced CSM (4 g, three times
per day, for 1 week); stool testing was performed on the 1-week
post-treatment samples. Levels of PFCs in serum, urine, sweat
and stool prior to and after treatment with CSM can be found in
Table 1.
After results were reviewed, it was felt that the PFC levels
from stool samples post-CSM intake provided justification for
a trial of ongoing treatment with CSM. Continuing after the 1-
week trial, the patient continued to take CSM (4 g, three times
per day) for approximately 20 consecutive weeks in order to
diminishhis body burden of PFCs. In December 2008, the patient
decided to try SPCs (from Yucca Schidigera Saponin: ‘Optimum
D-Tox’ brand; 8 drops, twice a day, for 1 week) and repeated the
stool sample in the same fashion. The carpets were removed
from the house on 20 January 2009, and subsequent testing
confirmed that the target PFCs found in the individual and
family members were isolatedfrom the air samples and carpet
in their home. After reading in the scientific literature that
another classof agents called zeolites hasthe ability to facilitate
removal of selected toxicant compounds by cation
exchange,
51,61,62
the patientalso elected in November2009 to try
a zeolite compound (zeolite-containing clinoptilolite: ‘Waiora’
brand; 3 drops, three times a day, for 1 week), and repeated the
stool sample before and after using the zeolite compound. No
other medications were being used at the time when SPCs or
zeolites were used. The patient and his family members intend
to pursue therapeutic intervention to eliminate accrued PFCs,
public health 124 (2010) 367–375370
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and to be followed to assess PFC levels in the months and years
to come.
PFC analysis
Formic acid (0.1 M) and a mixture of isotopically labelled PFCs
(Wellington Laboratories, Guelph, Ontario, Canada) were
added to 1.0 ml of serum, urine or sweat. The mixture was
vortexed, sonicated and subjected to solid-phase extraction.
The extract was concentrated to 100 ml and an instrument
performance internal standard was added along with 200 mlof
90% 20 mM acetic acid/10% methanol. For faecal PFC analysis,
methanol along with a mixture of isotopically labelled PFCs
was added to 1.0 g of freeze-dried stool. The mixture was
vortexed, sonicated and centrifuged. A known amount of the
extract was collected and concentrated to 100 ml on a nitrogen
evaporator; 200 ml of 90% 20 mM acetic acid/10% methanol and
instrument performance internal standard were added to the
vial. Analysis for each sample was performed by liquid chro-
matograph tandem mass spectrometry using multiple reac-
tion monitoring. Detection limits were 0.5 ng/ml for each
analyte, based on the lowest standard in the standard curve.
Procedural blanks were run with each set of samples, and
blanks were always below 0.5 ng/ml.
As mentioned, the extracts were concentrated to 100 ml.
To secure precision, the laboratory staff added 100 mlof
methanol and carefully marked the meniscus. When the
sample was concentrated, it was brought to the meniscus line
previously marked in order to keep the volumes reproducible.
The isotopically labelled standards used were: (i)
13
C
4
-PFOS,
sodium perfluoro-1-[1,2,3,4-
13
C
4
]octanesulfonate; (ii)
13
C
4
-PFOA,
perfluoro-n-[1,2,3,4-
13
C
4
]octanoic acid; (iii)
13
C
5
-PFNA, per-
fuloro-n-[1,2,3,4,5-
13
C
5
]nonanoic acid; and (iv)
13
C
2
-PFDA,
perfluoro-n-[1,2-
13
C
2
]decanoic acid. All of the standard calibra-
tion curves were linear.The standard concentrations usedwere:
(i) 0.5 ppb; (ii)2.0 ppb;(iii) 10.0 ppb; (iv) 30.0 ppb;and (v) 50.0 ppb.
Results and discussion
The PFC results for serum, urine, sweat and stool samples are
providedin Tables 1 and 2. The results of this case study suggest
that PFOA wasthe only PFC readily excretedin urine prior to any
therapeutic intervention. Only miniscule amounts of PFHxS
were detected in the sweat sample; no other PFCs were found in
sweat, thus PFCs did not appear to be excreted readily into
perspiration after sauna therapy and this was not investigated
further. Following SPC treatment, only miniscule amounts of
PFOA were detected in the faecal sample. No other PFCs were
detected, thus SPCs did not appear to facilitate considerable
excretion of PFCs into stool. Following zeolite treatment, only
minusculeamounts of PFOS were detected in the faecal sample;
no other PFCs weredetected, thus the type of zeolite used in this
case did not appear to facilitate considerable excretion of PFCs
into stool.
Prior to treatment by CSM, no PFCs were detected in stool.
Following CSM treatment, however, PFHxS, PFOS, PFOA and
PFNA were identified in both post-treatment faecal samples.
Serum levels repeated after 12 and after 20 weeks of CSM
treatment demonstrated an apparent decline in PFHxS, PFOS,
Table 1 – Level of perfluorinated compounds in serum, urine, sweat and stool prior to and after treatment withcholestyramine (CSM) and after treatment with zeolite
a
and
saponins.
a
Analyte Serum
(ng/g)
June 2007
Centile of serum
level according
to CDC reference
range data
39
Urine
(ng/ml)
June 2007
Sweat
(ng/g)
June 2007
Stool – no
treatment
(ng/g)
June 2008
Stool – after
treatment with
CSM – Sample
1 (ng/g)
June 2008
Stool – after
treatment with
CSM – Sample
2 (ng/g)
June 2008
Stool – after
treatment
with saponins –
Sample 1 (ng/g)
Feb 2009
Stool – after
treatment with
saponins –
Sample 2 (ng/g)
Feb 2009
Stool – after
treatment
with zeolite
(ng/g)
Nov 2009
PFHxS 60.00 >>95 centile <0.50 1.74 <0.50 5.73 5.62 <1.00 <1.00 <1.00
PFOS 26.00 50–75 centile <0.50 <0.50 <0.50 9.06 7.94 <1.00 <1.00 1.40
PFDS <0.50 – <0.50 <0.50 <0.50 <0.50 <0.50 <1.00 <1.00 <1.00
PFOA 6.80 75–90 centile 3.72 <0.50 <0.50 0.96 0.96 1.03 1.19 <1.00
PFNA 0.93 25–50 centile <0.50 <0.50 <0.50 0.55 0.54 <1.00 <1.00 <1.00
PFDA <0.50 – <0.50 <0.50 <0.50 <0.50 <0.50 <1.00 <1.00 <1.00
PFUA <0.50 – <0.50 <0.50 <0.50 <0.50 <0.50 <1.00 <1.00 <1.00
PFDoA <0.50 –<0.50 <0.50 <0.50 <0.50 <0.50 <1.00 <1.00 <1.00
PFHxS, perfluorohexansulfonate; PFOS, perfluorooctanesulfonate; PFOA, perfluorooctanoic acid; CDC, Centers for Disease Control and Prevention; PFDS, perfluorodecane sulfonate; PFNA, per-
fluorononanoic acid; PFDA, perfluorodecanoic acid; PFUA, perfluoro-n-undecanoic acid; PFDoA, perfluorododecanoic acid.
a The Limit of detection (LOD) for the urine, sweat and stool samples (other than the post-treatment stool with saponins) is 0.50 ng/g. The LOD for the stool samples after treatment with saponins and
zeolite is 1.00 ng/g. While the post-CSM stool sample was freeze-dried, the post-saponin and post-zeolite samples were extracted as wet samples and calculations were based on dry weight. As
a result, a lower extraction weight determined that the LOD had to go up slightly. Both methods worked well with the matrix spikes.
public health 124 (2010) 367–375 371
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PFOA and PFNA levels (Table 2). Use of CSM in this patient,
therefore, appears to be associated with and may facilitate
excretion of some bioaccumulated PFCs, most notably PFHxS,
PFOS and (perhaps) PFOA. Stool samples taken from another
family member using CSM for elevated serum PFCs also
showed significant excretion of these compounds into feces. As
PFCs are surfactants like endogenous bile acids, it is not
surprising that the CSM acts as a resin and interrupts recycling
of these compounds. Further study is required, however, to
determine the generalized applicability of these preliminary
findings to other PFC contaminated individuals.
With emerging evidence about the potential health sequelae
associated with human PFC accrual juxtaposed with (i) wide-
spread exposure to bioaccumulative PFCs in the general pop-
ulation, and (ii) select subgroups with sizeable exposures to
PFCs,
4
it behooves the medical and public health community to
delineate potential interventions which diminish the accumu-
lated load of these persistent toxicants. Although conclusive
generalized information cannot be gleaned from an individual
case history, the findings in this case report suggest that selected
bile acid sequestrants may have therapeutic value in the elimi-
nation of certain persistent PFCs within the human body. In order
to verify this, a carefully designed prospective research study
involving several PFC-contaminated participants is required.
In review, the question arises as to whether the CSM treat-
ment translated into significant reductions in the body burden
of PFCs. Accor ding to Table2, three consecutive values spanning
theyearfromJune2007toJune2008showednosubstantial
decline in serum levels of PFHxS and PFOS. However, within 3
months of BAS use, the levels of all elevated PFCs declined
steadily and consistently, despite ongoing exposure (as the
carpets were not yet removed). Accordingly, the treatment may
have been responsible for the reduction in serum levels. The
most compelling finding in this case, however, is that faecal
levels of PFCswere present with use of CSM.
Concluding thoughts
There is increasing global attention to the problem of persis-
tent pollutants and their sequelae, both in the environment
and within the human body.
1,63
Emerging research suggests
that accrued toxicants may lead to illness and increased
health risk throughout the life cycle.
3,63–65
With the 21st
century reality of escalating toxicant exposure and
bioaccumulation among individuals and population groups,
1
research is now underway to find potential interventions to
facilitate excretion of persistent toxicants in order to diminish
the body burden and to preclude or overcome associated
health problems (See Box 1).
66
Furthermore, some health
providers and researchers involved in molecular medicine
and environmental health sciences are recommending clin-
ical and laboratory assessment for individuals with possible
toxicant bioaccumulation,
67–69
and are exploring and
employing interventions to preclude and address such bio-
accumulation when possible.
41–43,48,49,66,70–79
As PFC human health research is a relatively new under-
taking, it remains to be seen to what extent these compounds
contribute to adverse health outcomes and human suffering.
While there is increasing evidence suggesting health sequelae
associated with PFC bioaccumulation, there are some authors
and publications that have minimized concern about the
accrual of these chemical agents. It is imperative to recognize
that much of the research related to potentially toxic
compounds, including PFCs, is undertaken or funded by the
specific companies, industry-supported organizations and
affiliated scientists involved with the production of the chem-
icals being studied. Furthermore, some toxicology journals
routinely use reviewers fromchemical companies to scrutinize
and review manuscript submissions about the compounds
their company manufactures.
With increasing attention to conflict of interest concerns,
80–84
the ongoing debate about how to approach the issue of patients’
health versus company profits,
81
and increasing awareness of
numerous egregiousviolations by some scientists and lobbyists
working to conceal industry culpability,
80
it is sometimes diffi-
cult to discern the credibility of research which has received
commercial funding from companies producing potentially
toxic agents. It is also problematic when credible papers high-
lighting potential sequelae of toxicant exposures are dismissed
because of commercial influence in the journal review process.
Therefore, it is recommended that regulatory intervention
be enacted whereby: (i) scientific journals require that
research be registered and funded through arms-length
independent research bodies where researchers, study
design, reporting and publication of evidence are not in
a conflict position, and are not acquiescent to the sway of
commercial power and influence; and (ii) scientists working
for industry be excluded from the peer review process of
papers related to their company’s products.
Table 2 – Serum levels of perfluorinated compounds prior to and after treatment with cholestyramine (CSM).
Analyte Serum
(ng/g)
June 2007
Prior to
treatment
Serum
(ng/g)
March 2008
Prior to
treatment
Serum
(ng/g)
June 2008
Immediately prior
to treatment
Serum (ng/g)
September
2008
After approx.
12 weeks
of CSM
treatment
Serum (ng/g)
November 2008
After approx.
20 weeks
of CSM
treatment
Carpets removed
from home
in January 2009
PFHxS 60.0 59.1 58.0 50.4 46.8 –
PFOS 26.0 27.4 23.0 15.6 14.4 –
PFOA 6.8 5.5 5.9 4.4 4.1 –
PFNA 0.9 0.7 0.5 <0.5 <0.5 –
PFHxS, perfluorohexansulfonate; PFOS, perfluorooctanesulfonate; PFOA, perfluorooctanoic acid; PFNA, perfluorononanoic acid.
public health 124 (2010) 367–375372
Author's personal copy
In the literature, there are no reported studies of successful
interventions to remove PFCs from the human body. Exposure
to these commonly used non-stick and stain-resistant
compounds is widespread, but excretion from the body is
impaired as a result of the chemical nature of some of these
agents and their propensity to be re-absorbed in the kidney and
the enterohepatic circulation. With emerging evidence about
the possible toxicity associated with accrual of PFCs, inter-
ventions to hasten removal in individuals with high levels may
be indicated. This paper presents a case history suggesting that
treatment with CSM may facilitate elimination of commonly
encountered PFCs, including PFOA, PFOS and PFHxS. Sauna
depuration, treatment with SPCs and use of zeolites do not
appear to be effective means of facilitating the excretion of
PFCs. Other interventions, such as therapeutic apheresis,
which have the ability to remove protein-bound toxicants
warrant investigation as potentially rapid methods of elimi-
nating PFCs.
66
Further study is required, but the use of selected
BASs such as CSM shows promise as one type of possible
intervention for facilitating the elimination of PFCs in humans.
Acknowledgements
The authors wish to thank Dr. Jonathan W. Martin from the
Department of Laboratory Medicine and Pathology at the
University of Alberta for providing important suggestions on
the preparation of this manuscript.
Ethical approval
Details of institutional review board approval discussed in the
text.
Competing interests
None declared.
Funding
None declared.
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