Hindawi Publishing Corporation ISRN Toxicology Volume 2013, Article ID 657849, 8 pages http://dx.doi.org/10.1155/2013/657849 Research Article Gastrointestinal Elimination of Perfluorinated Compounds Using Cholestyramine and Chlorella pyrenoidosa Stephen J. Genuis,1 Luke Curtis,2 and Detlef Birkholz3 1 Faculty of Medicine, University of Alberta, 2935-66 Street, Edmonton, AB, Canada T6K 4C1 2 Forest Hills, NY 11375, USA 3 ALS Laboratory Group, University of Alberta and Environmental Division, Edmonton, AB, Canada T6E 5C1 Correspondence should be addressed to Stephen J. Genuis; [email protected] Received 8 June 2013; Accepted 4 August 2013 Academic Editors: Y. C. Hseu and T. E. Stoker Copyright © 2013 Stephen J. Genuis et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. While perfluorinated compounds (PFCs) are a family of commonly used synthetic compounds with many applications, some PFCs remain persistent within the human body due, in part, to enterohepatic recirculation and renal tubular reabsorption. With increasing recognition of potential harm to human health associated with PFC bioaccumulation, interventions to facilitate elimination of these toxicants are welcome in order to potentially preclude or overcome illness. Minimal research has been undertaken thus far on methods to accelerate human clearance of PFCs. Methods. To test for possible oral treatments to hasten PFC elimination, a group of individuals with elevated PFC levels was treated with cholestyramine (CSM) and, after a break, was subsequently treated with Chlorella pyrenoidosa (CP).Stoolsampleswerecollectedfromallparticipants(i)priortoanytreatment, (ii) during treatment with CSM, and (iii) during treatment with CP. Results. With CSM treatment, significant levels of three distinct PFCs were found in all stools, while levels were mostly undetectable prior to treatment. Following treatment with oral CP, undetectable or very low levels of all PFCs were noted in each sample tested. Conclusion. CSM appears to facilitate elimination of some common PFCs and may have some role in the clinical management of patients with accrued PFCs. 1. Introduction and Background withstand the extremes of temperature, pH, and oxidizing conditions. Perfluorinated compounds (PFCs) are a group of anthro- pogenic chemicals with many useful applications, includ- 1.1. Human PFC Exposure. With a number of useful appli- ing repelling stains on furniture/carpets/clothing as well cations, PFC compounds have come into common use in as securing nonadherence in food packaging and nonstick western culture. Human exposure in domestic and com- cooking surfaces. Structurally, these compounds consist of mercial settings has occurred as a result of processes such a linear or branched carbon backbone, that is, entirely as inhalation of contaminated air, ingestion of tainted dust substituted by strong bonds fluorine atoms. The fluorine and foodstuffs, and dermal absorption in treated clothing. component of PFCs provides extremely low surface tension With inherent chemical stability and slow elimination from and accounts for their unique hydrophobic (water repelling) the human body, accrual of these persistent compounds andlipophobic(lipidrepelling)natures[1]. These compounds continues in the population at large [2]. In addition, spills of differ markedly from most other chemical surfactants in PFCs have occurred where individuals have been exposed to that they are very stable, nonreactive, and effective at low elevated levels of these agents through avenues such as the concentrations. With these unique properties, selected PFCs water supply [3]. Furthermore, high levels of PFC exposures have been used to make commercial products that are have been reported in drinking water sources located near resistant to both water and oil, are stain resistant, and can also plants manufacturing PFCs [4]. 2 ISRN Toxicology Relatively high levels of PFCs have also been found in PFOA [16]. A recent case-control study reported the finding the Greenlandic Inuit and other circumpolar populations of significantly higher PFOA and PFOS serum levels in who consume large quantities of fish and marine mam- women with surgically treated endometriosis as compared to mals contaminated with PFCs [5]. In the general western matchedcontrolwomen[17]. Studies examining associations population, it is estimated that diet provides most (∼91% between serum PFC levels and human semen studies have Perfluorooctane sulfonate (PFOS); ∼99% Perfluorooctanoic been inconsistent, with some studies reporting significantly acid (PFOA)) of the total PFC intake. In some groups, lower levels of morphologically normal sperm cells in men however, drinking water as well as indoor air and house with higher serum PFC levels and other studies showing dust can also provide significant PFC exposure [6]. Human little relationship [18]. A study of 169 young Danish men studies have also reported that PFCs can cross the placenta (aged19to21years)fromapregnancycohortreported and are present in breast milk [7, 8]. One study reported that higher in-utero exposure to PFOA (as measured by significant declines in serum PFOS in breastfeeding mothers maternal serum samples at the 30th week of pregnancy) [8], presumably due to vertical transmission of some PFCs was associated with significantly lower sperm counts and into the infant via breast milk. significantly higher levels of luteinizing hormone and follicle- Some human studies have reported significantly stimulating hormone [19]. Exposure to certain PFCs has also higher mean levels of serum PFC in males versus females been linked to reproductive and developmental problems in (NHANES) [2]. The precise reason for the variance has not animal studies [1]. been confirmed but may be due, in part, to PFC losses with Exposure to perfluorinated compounds may be associ- regular menstrual bleeding and through breast feeding. ated with adverse cardiovascular outcomes and dysregulation These routes of bioelimination likely account for the finding of body weight. A confounder adjusted study of 1,216 US that, in postmenopausal women, a Japanese study reported adults reported significantly higher levels of cardiovascular that serum levels of PFOA and PFOS were higher compared disease (including heart diseases, stroke and peripheral vas- to menstruating premenopausal women [9]. cular disease) in subjects with higher serum PFOA concen- trations [20]. A study of 664 young subjects (aged 12 to 1.2. PFC Persistence in Humans. Some of the various subtypes 30 years) reported that higher serum levels of PFOS were within the PFC family include (i) PFHxS (perfluorohexane associated with significantly thickened carotid artery intima- sulfonate), (ii) PFOS (perflurooctane sulfonate), (iii) PFOA media thickness (CIM) [21]. A study with lab mice reported (perfluorooctanoic acid) and (iv) PFNA (perfluorononanoic that low-level oral PFOA exposure was associated with acid). Each of the individual PFCs has unique properties significantly higher body weights and significantly higher pertaining to toxicokinetics and bio-elimination. In general, levels of leptin and insulin as compared to unexposed mice PFCs are eliminated very slowly in humans. Various human [22]. More recently, newly published research has suggested studies have estimated plasma half-lives of PFCs to be about a link between human serum concentrations of PFOS, and 8.5to8.8yearsforPFHxS(range2.8–27years),5.4yearsfor PFOA and the development of osteoarthritis [23]. PFOS (range 2.4 to 21.7 years), and 2.3 to 3.8 years for PFOA Several animal studies have reported that higher exposure (range 1.5 to 9.1 years) [10, 11]. to PFCs is associated with neurotoxicity [24]. A study of 10,546 children in the Ohio Valley reported that higher serum Unlike fat-soluble lipophilic compounds such as levels of PFHxS were associated with significantly higher risk organochlorine pesticides and polychorinated biphenyls of attention deficit hyperactivity disorder (ADHD), while (PCBs) which tend to accumulate in adipose tissue, higher serum levels of PFOA, PFOS or PFNA were not perfluorinated compounds tend to persist in bile as well as in associatedwithhigherratesofADHD[25]. Another study of lean human tissue including muscle, liver, and kidney [12]. 571childrenaged12to15yearsreportedthathigherserum Much of the total body burden of PFCs remains in blood levels of PFOA, PFOA, and PFHxS were all individually bound to plasma proteins [12]. associated with significantly higher rates of ADHD [26]. A cross-sectional study of 1,766 US adults aged 60 to 85 years 1.3. Emerging PFC Health Concerns. Recent research has reported that higher levels of PFOS, PFOA, PFNA and PFHxS uncovered assorted health concerns related to exposure and were associated with modest yet nonsignificantly lower rates accrual of PFCs, including issues related to gestational and of cognitive limitation [27]. prenatal contamination. In addition, animal and human stud- A recent case-control study among the Greenlandic Inuit ies have now linked PFC exposure with developmental toxi- reported that higher serum PFC levels were linked to signif- city, neurotoxicity, hepatotoxicity, carcinogenicity, metabolic icantly higher risk of breast cancer [1]. Studies on chemical dysregulation, immunotoxicity, and endocrine disruption. industry workers have reported that occupational