Perfluorinated compounds (PFCs) are a group of anthropogenic chemicals with many useful applications, including repelling stains on furniture/carpets/clothing as well as securing nonadherence in food packaging and nonstick cooking surfaces. Structurally, these compounds consist of a linear or branched carbon backbone, that is, entirely substituted by strong bonds fluorine atoms. The fluorine component of PFCs provides extremely low surface tension and accounts for their unique hydrophobic (water repelling) and lipophobic (lipid repelling) natures [
With a number of useful applications, PFC compounds have come into common use in western culture. Human exposure in domestic and commercial settings has occurred as a result of processes such as inhalation of contaminated air, ingestion of tainted dust and foodstuffs, and dermal absorption in treated clothing. With inherent chemical stability and slow elimination from the human body, accrual of these persistent compounds continues in the population at large [
Relatively high levels of PFCs have also been found in the Greenlandic Inuit and other circumpolar populations who consume large quantities of fish and marine mammals contaminated with PFCs [
Some human studies have reported significantly higher mean levels of serum PFC in males versus females (NHANES) [
Some of the various subtypes within the PFC family include (i) PFHxS (perfluorohexane sulfonate), (ii) PFOS (perflurooctane sulfonate), (iii) PFOA (perfluorooctanoic acid) and (iv) PFNA (perfluorononanoic acid). Each of the individual PFCs has unique properties pertaining to toxicokinetics and bio-elimination. In general, PFCs are eliminated very slowly in humans. Various human studies have estimated plasma half-lives of PFCs to be about 8.5 to 8.8 years for PFHxS (range 2.8–27 years), 5.4 years for PFOS (range 2.4 to 21.7 years), and 2.3 to 3.8 years for PFOA (range 1.5 to 9.1 years) [
Unlike fat-soluble lipophilic compounds such as organochlorine pesticides and polychorinated biphenyls (PCBs) which tend to accumulate in adipose tissue, perfluorinated compounds tend to persist in bile as well as in lean human tissue including muscle, liver, and kidney [
Recent research has uncovered assorted health concerns related to exposure and accrual of PFCs, including issues related to gestational and prenatal contamination. In addition, animal and human studies have now linked PFC exposure with developmental toxicity, neurotoxicity, hepatotoxicity, carcinogenicity, metabolic dysregulation, immunotoxicity, and endocrine disruption.
High serum PFC levels in women, for example, have been linked to significantly lower fertility rates in a large Norwegian study [
Exposure to perfluorinated compounds may be associated with adverse cardiovascular outcomes and dysregulation of body weight. A confounder adjusted study of 1,216 US adults reported significantly higher levels of cardiovascular disease (including heart diseases, stroke and peripheral vascular disease) in subjects with higher serum PFOA concentrations [
Several animal studies have reported that higher exposure to PFCs is associated with neurotoxicity [
A recent case-control study among the Greenlandic Inuit reported that higher serum PFC levels were linked to significantly higher risk of breast cancer [
A number of experimental studies have reported that bioaccumulation of PFCs at levels comparable to highly exposed humans can reduce immune function in rats and mice [
Furthermore, a recent paper discusses the impact of PFCs on the functioning of sex hormone receptors. PFHxS, PFOS, and PFOA all significantly impact estrogen receptors, and antagonize androgen receptors in a concentration-dependent manner [
While there has been little attention in scientific research to clinical detoxification [
CSM and other bile acid sequestrants like colestipol and colesevelam are positively charged nondigestible resins that bind to enterohepatic bile acids in the intestines, forming an insoluble complex excreted in feces. CSM is primarily used for reducing serum LDL-cholesterol levels; various studies have reported that CSM lowers LDL-cholesterol levels by 12–20% [
CSM has also been hypothesized to reduce body burdens of fat-soluble toxins via the binding of lipophilic compounds to prevent reabsorption through the enterohepatic pathway, although published data is rather scarce. In 1984, the use of oral CSM in lab rats was reported to significantly increase levels of PFOA and PFOS in feces by about 10-fold [
CSM has also been demonstrated to reduce zearalenone (a mycotoxin produced mainly by the fungi
Other potential detoxification modalities remain untested in relation to PFC elimination. Oral clay has been reported to reduce body burdens of mycotoxins such as aflatoxins and fumonisins in lab animals and humans [
As part of their clinical assessments, individuals presenting to an environmental health clinic in Edmonton, Alberta, Canada, are assessed for evidence of toxicant exposure and bioaccumulation of potentially toxic compounds. If individuals have a history of potential exposure, PFC testing is undertaken. If a patient is found to have bioaccumulated high PFC levels, PFC testing is also discussed and offered to family members who have sustained similar exposure. Eight individuals with elevated PFC burdens were thus identified—4 females and 4 males were included in the study. This recruitment was a selection of convenience as these individuals were found to have elevated levels and all were keen to participate. As part of the effort to diminish their PFC burden, two unrelated detoxification agents—CSM and CP—were offered as potential therapeutic clinical modalities to possibly facilitate elimination of their PFC burden It was difficult to anticipate efficacy of such interventions as PFCs tend to repel both lipophilic and hydrophilic compounds in their function as stain-resistant compounds.
All 8 individuals were completely informed of the available information in the literature about known risks of PFCs, the lack of known interventions to facilitate PFC removal, and the experience discussed in the literature in relation to CSM and Chlorella. After considering the potential health concerns associated with PFHxS, each patient was very keen to participate. There was a particular unease about potential neurotoxic effects as each of the women with elevated PFHxS indicated concern about the possibility of vertical transmission in future pregnancies [
Stool collection was obtained from each participant prior to any intervention and analyzed for levels of 4 common PFCs: PFHxS, PFOA PFOS, and PFNA. Each participant was then treated with CSM (4 grams once per day for one week). A break of three weeks ensued and then each participant was subsequently treated with CP (9 grams three times per day for one week). Stool samples were collected from all 8 patients on three occasions: (i) before the start of any therapy, (ii) while taking CSM but after using it for at least 5 consecutive days, and (iii) while taking CP but after using it for at least 5 consecutive days. Serum PFC levels were assessed prior to and subsequent to the stool testing to confirm that each PFC compound found in stool was present in each patient’s serum both prior to, and following the interventions.
Stool samples were collected in a 500 mL glass jar obtained from ALS Laboratories. Samples were provided directly into the glass jars. Each of the glass bottles used for sampling was provided by ALS Laboratories and had undergone extensive cleaning and rinsing. The containers were deemed appropriate for collection with negligible risk of contamination: laboratory-grade phosphate-free detergent wash, acid rinse, multiple hot and cold deionized water rinses, oven-dried, and capping and packing in quality controlled conditions. Samples were delivered to the physician who provided them to ALS Laboratories for testing.
For fecal PFC analysis, methanol along with a mixture of isotopically labeled 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
Detection limits were 0.5 ng/g 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/g. As mentioned, the extracts were concentrated to 100
PFC results prior to and after treatment are given in Tables
Removal of persistent perfluorinated compounds with cholestyramine (CSM) and
Subject | Type of test | PFHxS | PFOS | PFOA | PFNA |
---|---|---|---|---|---|
#1 female 48 | Serum | 16.3** | 5.67 | 1.27 | 0 |
Pretreatment stool | 1.0 | <1.0 | <1.0 | <1.0 | |
Post-CSM stool | 3.4 | 1.0 | 1.1 | <1.0 | |
Post-CP stool | <1.0 | <1.0 | <1.0 | <1.0 | |
| |||||
#2 female 24 | Serum | 35.8** | 26.5 | 2.17 | 0 |
Pretreatment stool | <1.0 | <1.0 | <1.0 | <1.0 | |
Post-CSM stool | 460 | 2.1 | 2.1 | <1.0 | |
Post-CP stool | <1.0 | <1.0 | <1.0 | <1.0 | |
| |||||
#3 female 22 | Serum | 44.1** | 27.3 | 2.33 | 0.74 |
Pretreatment stool | <1.0 | 1.4 | <1.0 | <1.0 | |
Post-CSM stool | 16 | 5.3 | <1.0 | <1.0 | |
Post-Chlorella stool | <1.0 | 1.1 | <1.0 | <1.0 | |
| |||||
#4 female 20 | Serum | 97.5** | 44.7 | 5.04 | 0.62 |
Pretreatment stool | 1.7 | 1.5 | <1.0 | <1.0 | |
Post-CSM stool | 26.6 | 36.9 | 2 | <1.0 | |
Post-CP stool | 1.1 | <1.0 | <1.0 | <1.0 |
Removal of persistent perfluorinated compounds with cholestyramine and chlorella—male Subjects.
Subject | Type of test | PFHxS | PFOS | PFOA | PFNA |
---|---|---|---|---|---|
#5 male 54 | Serum | 34.5** | 8.58 | 1.97 | 0 |
Pretreatment stool | <1.0 | <1.0 | <1.0 | <1.0 | |
Post-CSM stool | 59.4 | 4.1 | <1.0 | <1.0 | |
Post-CP stool | <1.0 | <1.0 | <1.0 | <1.0 | |
| |||||
#6 male 25 | Serum | 30.3** | 11.3 | 3.99 | 0.89 |
Pretreatment stool | 1 | 1.3 | <1.0 | 1.1 | |
Post-CSM Stool | 13.7 | <1.0 | 1.4 | <1.0 | |
Post-CP Stool | <1.0 | <1.0 | <1.0 | <1.0 | |
| |||||
#7 male 19 | Serum | 92.1** | 58.8 | 5.13 | 0.54 |
Pretreatment stool | 1.1 | <1.0 | <1.0 | <1.0 | |
Post-CSM Stool | 30.1 | 23.4 | 1.2 | <1.0 | |
Post-CP Stool | <1.0 | <1.0 | <1.0 | <1.0 | |
| |||||
#8 male 17 | Serum | 46.5** | 37.5 | 3.99 | 0 |
Pretreatment stool | 1.8 | <1.0 | <1.0 | <1.0 | |
Post-CSM Stool | 24.7 | 4.5 | 1.3 | <1.0 | |
Post-CP Stool | 1.2 | <1.0 | <1.0 | <1.0 |
Mean levels of PFCs in serum prior to treatment and stool after CSM treatment.
PFC species |
Pretreatment serum PFC species in ng/g |
Stool PFC post-CSM in ng/g |
| |||
---|---|---|---|---|---|---|
Female | Male | Female | Male | Female | Male | |
PFHxS | 48.4 (34.7) | 50.8 (28.3) | 126 (222) | 32 (19.5) | 2.60 | 0.63 |
PFOS | 26 (23.7) | 29 (23.7) | 11.3 (17.1) | 8.2 (10.2) | 0.43 | 0.28 |
PFOA | 2.7 (1.6) | 3.8 (1.3) | 1.4 (0.76) | 1.1 (0.41) | 0.52 | 0.29 |
PFNA | 0.34 (0.40) | 0.36 (0.44) | 0.5* | 0.5* | N/A | N/A |
NHANES serum levels—all ages—2009 to 2010 [
PFHxS | PFOS | PFOA | PFNA | |||||
---|---|---|---|---|---|---|---|---|
Female | Male | Female | Male | Female | Male | Female | Male | |
Geometric mean | 1.72 | 2.17 | 18.4 | 23.2 | 3.50 | 4.47 | 0.861 | 1.09 |
50% percentile | 1.60 | 2.10 | 18.2 | 23.9 | 3.60 | 4.60 | 0.900 | 1.10 |
75% percentile | 2.90 | 3.40 | 27.4 | 32.2 | 5.20 | 6.30 | 1.30 | 1.60 |
90% percentile | 5.80 | 6.10 | 39.8 | 45.3 | 7.10 | 8.40 | 2.20 | 2.40 |
95% percentile | 8.20 | 8.50 | 46.6 | 62.7 | 8.60 | 10.7 | 3.00 | 4.00 |
As reported in Tables
The reason why the study population has such high PFHxS levels relative to the NHANES population may be related to ongoing exposure to carpet repeatedly treated with stain-resistant treatment with in-floor radiant heating under the carpeted floor in each case. Beesoon et al. [
Despite abundant PFCs in serum, none of the participants showed evidence of noteworthy gastrointestinal elimination of any of the PFCs tested prior to treatment, with all levels in fecal samples below or just above the detection limits. After treatment with CSM, significant levels of PFHxS were found in the stools of all 8 patients, with patient #2 having a stool concentration of 460 ng/g PFHxS. Significant post-CSM stool levels of PFOS and PFOA were also seen in most of the patients, while no detectable PFNA was seen in the stools of any of the patients. Perhaps the effectiveness of the CSM was limited by the low initial concentrations of PFNA. The effectiveness of PFC removal by CSM varied from patient to patient, but each showed evidence of noteworthy PFC elimination when treated with CSM.
Figure
Ratio of PFCs in stool following CSM treatment versus pre-treatment serum.
Table
Despite the suggestive evidence that CSM is effective at facilitating the release of PFCs, this retrospective analysis has limitations. One limitation might involve the potential nonhomogeneity of stool samples, as PFC concentrations may vary from site to site within any given stool sample, which may alter numerical results. Furthermore, without precise knowledge of the preexisting body burden, it is not possible to determine the rate of decline by analyzing the concentration in stool. Thus, the total amount or rate of PFC excretion following CSM therapy is not quantified.
Ongoing serum PFC levels for each patient were not presented in this report. Consecutive serum PFC levels taken over a short period of time do not correlate precisely with changes in body burden for several reasons. Toxicokinetics of most adverse chemical compounds are not completely understood and PFC levels within a given body compartment can fluctuate. Tissue and serum levels do not maintain a steady equilibrium, with a potential for rapid mobilization of toxicants from one compartment to another. Levels of some compounds within a single compartment can multiply quickly in response to various determinants potentially including fever, exercise, or a shift in caloric status [
PFCs accumulate in human blood and tissues, have long elimination half-lives, and are increasingly linked to assorted health concerns. Recent evidence confirms that many people within the general population have had exposure to, and bioaccumulation of PFCs within their body. Interventions are needed to facilitate removal of PFCs in order to preclude the development of health sequelae related to accrual of these toxicant compounds, including outcomes resulting from gestational exposures in reproductive-aged women. Thus far, there is minimal research on interventions to facilitate elimination of these compounds. Although the scale of elimination in relation to the accumulated PFC body burden cannot be quantified by this preliminary study, these findings provide compelling evidence that oral cholestyramine is effective at hastening elimination of various PFCs from the human body, particularly PFHxS. Oral
Cholestyramine (CSM) appears to be an effective agent for facilitating the gastrointestinal excretion of PFHxS, PFOA, and PFOS.
The authors declare that there is no conflict of interests. No funding has been received for any part of this work.
Sincere thanks to Daniel Eriksson for his assistance in preparing the final draft for publication.