Review
Perfluorinated compounds – Exposure assessment for the general population in western countries

https://doi.org/10.1016/j.ijheh.2008.04.007Get rights and content

Abstract

Perfluorinated compounds (PFCs) can currently be detected in many environmental media and biota, as well as in humans. Because of their persistence and their potential to accumulate they are of toxicological concern. The present review presents the current knowledge of PFC monitoring data in environmental media relevant for human exposure. In this context, PFC concentrations in indoor and ambient air, house dust, drinking water and food are outlined. Furthermore, we summarize human biomonitoring data of PFC levels in blood, breast milk, and human tissues. An estimate of the overall exposure of the general adult population is provided and compared with tolerable intake values.

Using a simplified model, the average (and upper) level of daily exposure including all potential routes amounts to 1.6 ng/kgbody weight (8.8 ng/kgbody weight) for PFOS and 2.9 ng/kgbody weight (12.6 ng/kgbody weight) for PFOA in adults in the general population. The majority of exposure can be attributed to the oral route, mainly to diet. Overall, the contribution of PFOS and PFOA precursors to total exposure seems to be limited.

Besides this background exposure of the general population, a specific additional exposure may occur which causes an increased PFC body burden. This has been observed in populations living near PFC production facilities or in areas with environmental contamination of PFCs. The consumption of highly contaminated fish products may also cause an increase in PFC body burdens.

Introduction

Perfluorinated compounds (PFCs) represent a large group of chemicals which are characterized by a fully fluorinated hydrophobic linear carbon chain attached to various hydrophilic heads. The chemical structures of some important PFCs are given in Fig. 1. PFCs have been produced since the 1950s and are widely used for many industrial purposes and consumer-related applications. This is due to their unique physico-chemical characteristics such as chemical and thermal stability, low surface free energy and surface active properties (Hekster et al., 2003; Lehmler, 2005). The C–F bond is particularly strong, and is resistant to various modes of degradation, including reaction with acids and bases, oxidation, and reduction (Kissa, 2001). This resistance contributes to the extraordinary stability of PFCs. While some PFCs undergo chemical transformations, these reactions occur mainly at the hydrophilic portions of the molecule, as opposed to the perfluorinated alkyl chains. The most commonly studied PFC substances are the perfluorinated sulfonates and the perfluorinated carboxylates. Among these, perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) are of greatest concern. Both persist in humans and the environment.

PFOS, its precursors, and related compounds are used in many applications ranging from oil and water repellant coatings for carpets, textiles, leather, paper, cardboard, and food packing materials; electronic and photographic devices; and surfactants in diverse cleaning agents, cosmetics, and fire-fighting foams (OECD, 2002; Kissa 2001). PFOA, as its ammonium salt, is mainly used as an essential processing aid in the manufacture of certain fluoropolymers such as polytetrafluoroethylene (PTFE) and to a lesser extent in industrial applications as an antistatic additive and in the electronic industry (OECD, 2005).

There are two main processes used to commercially synthesize PFCs. PFOS, along with some other PFCs, are commercially synthesized by a process known as electrochemical fluorination (ECF), which uses an electric current to fully fluorinate organic feedstock dispersed in liquid hydrogen fluoride. During this non-selective process, the predominant perfluorinated alkyl chain length produced corresponds to the alkyl chain length of the organic feedstock used. However, other perfluoroalkyl homologues are also formed during ECF. For example, ECF of octanesulfonyl fluoride produces perfluorooctanesulfonyl fluoride (PFOSF) plus homologous sulfonyl fluorides and related fluorocarbons containing between 4 and 13 carbon atoms. Reaction by-products also include branched chain isomers. The resulting substances derived from various reactions with PFOSF, mainly perfluorooctane sulfonamides and perfluorooctane sulfonamide derivatives, are building blocks for different commercial perfluoroalkyl substances.

The other major commercially important process for PFC synthesis is telomerization. In this process, tetrafluoroethylene reacts with intermediate perfluoroalkyl iodides to form key compounds like fluoroalkyl silanes, carboxylates, acrylates and methacrylate polymers (Schultz et al., 2003). Branched chain isomers are not observed in the products formed by telomerization (Kissa, 2001).

The more persistent PFCs, such as PFOS and PFOA, can also be formed in the environment from abiotic and biotic transformation of commercially synthesized precursors. During ECF and subsequent commercial reactions, numerous substances such as perfluoroalkylsulfonamide alcohols were unintentionally produced, or remained as by-products in commercial products. Most of these substances can be converted in the ecosystem and in living organisms to persistent PFCs. For example, it has been demonstrated that perfluorooctane sulfonamides can be metabolized to PFOS (Xu et al., 2004; Tomy et al., 2004). It has to be noted that PFOS may therefore be the final degradation or metabolic product of many perfluorooctylsulfonyl substances (Hekster et al., 2003).

In addition, some precursors like fluorotelomer alcohols (FTOH) will be subsequently transformed into PFOA under environmental degradation processes (Ellis et al., 2004; Dinglasan et al., 2004; Wang et al., 2005). Furthermore, there is growing evidence from some studies that 8:2 FTOH is converted to PFOA after oral uptake in mice (Kudo et al., 2005; Henderson and Smith, 2007) and rats (Fasano et al., 2006; D’eon and Mabury, 2007). These findings were confirmed by in vitro studies using rat hepatocytes (Martin et al., 2005) and hepatocytes and microsomes from various species (Nabb et al., 2007) to study the metabolism of 8:2 FTOH.

From a regulatory point of view, PFOS is classified as very persistent, very bioaccumulative and toxic, thus fulfilling the criteria for being considered as a persistent organic pollutant under the Stockholm Convention (EU, 2006). In the European Union, the use of PFOS has been restricted and the PFOS Directive aims to end the use of all PFOS as soon as practical (EU, 2006). In particular, fire-fighting foams that have been placed on the market before 27 December 2006 can be used until 27 June 2011. Similar regulatory action has been taken in North America. In Canada, PFOS, its precursors, and salts are are being considered for addition to the list of Toxic Substances under the Canadian Environmental Protection Act 1999 (Government of Canada, 2006). This action would prohibit the manufacture, use, sale, offer for sale and import of PFOS, as well as manufactured items containing the perfluorooctylsulfonyl moiety. The United States Environmental Protection Agency (US EPA) has adopted federal Significant New Use Rules for PFOS and related substances for new manufacturers and new uses of these substances. These rules will allow the US EPA to evaluate any intended new uses, and subsequently restrict or prohibit these new uses.

In addition, one of the primary manufacturers of fluorinated chemicals in North America announced a cease in production of perfluorooctanesulfonyl compounds in 2000. It was projected that from 2000 to 2002, the production of C8F17SO2-containing compounds for US Food and Drug Administration-approved uses would decrease from 1,520,000 to 0 kg (US EPA 2002).

The toxicity of PFOS and PFOA has been studied extensively, mainly in rodents. Several reviews are available that discuss results from these studies (OECD, 2002; Kennedy et al., 2004; US EPA, 2005; Harada et al., 2005b; Andersen et al., 2008; Lau et al., 2007). Hepatotoxicity, developmental toxicity, immunotoxicity, hormonal effects and a carcinogenic potency are the effects of main concern. In contrast, epidemiologic data related to PFC exposure are limited. The data were collected mainly among PFC production plant workers and have not found consistent effects on morbidity and mortality in humans.

The persistence of PFCs in the environment, plus their potential to accumulate in organisms and to biomagnificate in the food chain is of particular toxicological concern. Several PFCs have been detected in nearly all environmental media and biota reflecting the widespread global pollution in all parts of the ecosystem (Giesy and Kannan, 2001). PFCs have also been detected in human blood and tissue samples from occupationally and non-occupationally exposed humans throughout the world. The persistence of certain PFCs may be a more relevant issue for humans versus other species. In contrast to investigations carried out in laboratory animals in which short half-lives of PFCs were observed, studies in retirees from PFC production facilities showed a mean elimination half-life of 3.8 years (PFOA) and 5.4 years (PFOS) (Olsen et al., 2007b). A widespread distribution of various PFCs and their corresponding degradation and metabolism products results in a very complex exposure situation. The contribution of single sources and pathways to the total exposure is currently not well defined.

The aim of this review was to compile in detail the current data available to define the environmental media responsible for human exposure to PFCs. For this purpose we used the results of different Medline inquiries to get an overwiew of the current scientific literature. We also included papers presented at conferences, reports from governmental, scientific and other institutions, and where possible, unpublished reports and other gray literature. In this context PFC concentrations in indoor and ambient air, house dust, drinking water, and food are outlined. Furthermore, we will summarize human biomonitoring data in blood, breast milk and human tissues. Current estimates of the overall exposure of the adult general population will also be addressed. All these data will be discussed in relation to present benchmark values used for risk assessment.

Section snippets

Environmental monitoring

For the assessment of human exposure to PFCs, different pathways have to be considered. Exposure via inhalation may result from outdoor air and indoor air PFC pollution, and from PFC in house dust. Oral exposure is mainly determined by contamination of food and drinking water. Ingestion of dust and soil due to hand-to-mouth activities may also contribute to the internal exposure for children. However, this paper will focus mainly on exposure pathways of adults. Data from PFC monitoring in

Contamination of food and drinking water

Although dietary intake is assumed to be a major route of exposure for the general population, only few systematic data on PFC levels in foods are available. Often ecological or ecotoxicological questions are the focus of investigations on animals, so that information on the contamination of edible parts cannot be deduced. More detailed data are only available for PFC levels in fish, mainly in the context of surveys of fish caught in PFC-contaminated waters.

Human biomonitoring

Usually the internal exposure of PFCs is estimated based on concentrations in plasma, serum, or whole blood. Validation studies have shown that serum and plasma samples yield comparable results regarding PFOS, PFOA, and PFHxS concentrations (Ehresman et al., 2007). As yet, it was assumed that levels in whole blood are 50% below levels in serum or plasma, although the current results are not consistent. Samples with widely differing concentrations were analyzed by Ehresman et al. (2007) and a

Breast milk

The mechanism by which perfluorinated substances are transferred from mother's blood to breast milk is not clear. But it is well known that PFCs are strongly bound to the protein fraction in blood (Han et al., 2003). The possibility of PFCs entering the milk and accumulating to levels observed in maternal plasma is therefore limited.

Up to now, PFOS and PFOA levels during lactation have been studied in two animal studies (Kuklenyik et al., 2004; Hinderliter et al., 2005). Testing an analytical

Overall exposure assessment for adults

The widespread exposure of children and adults all over the world to PFCs suggests that the observed human body burdens are due to a ubiquitous source. With regard to the chemical and physical properties of PFCs, there are different possible routes for the assimilation of PFCs into the body. One set of routes is direct exposure to these substances via inhalation of air, ingestion of house dust, drinking water and food. With regard to the latter, we have to keep in mind that PFCs could be

Conclusion

For risk assessment purposes our exposure estimates could be compared to tolerable lifetime intake levels at which no appreciable health risks would be expected over a lifetime. Beyond this we compared our data to the tolerable daily intakes (TDI) recommended by scientific institutions.

A recent evaluation of PFOS was performed by the UK Committee on Toxicity of Chemicals in Food, Consumer Products and the Environment (COT (Committee on Toxicity of Chemicals in Food and Consumer Products and The

Acknowledgment

We greatly thank Martin Schlummer and Jan Ungewiß (Fraunhofer-Institute for Process Engineering and Packaging, Freising, Germany) and Annika Jahnke (Department of Applied Environmental Sciences ITM, Stockholm, Sweden) for their important support.

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