Isomers of perfluorooctanesulfonate and perfluorooctanoate and total perfluoroalkyl acids in human serum from two cities in North China

Abstract

The sources and pathways of human exposure to perfluoroalkyl acids (PFAAs) are not well characterized, particularly in China where many perfluorinated substances are now manufactured. Here, isomer-specific PFAA analysis was used for the first time to evaluate exposure sources for Chinese people, by applying the method to 129 serum samples collected in two typical cities (Shijiazhuang and Handan) in North China. Among all samples, total perfluorooctanesulfonate (∑PFOS, mean 33.3 ng/ml) was the predominant PFAA followed by perfluorohexanesulfonate (2.95 ng/ml), total perfluorooctanoate (∑PFOA, 2.38 ng/ml), and perfluorononanoate (0.51 ng/ml). The level of ∑PFOS was higher than in people from North America in recent years. The mean concentrations of ΣPFAAs in the participants living in urban Shijiazhuang (59.0 ng/ml) and urban Handan (35.6 ng/ml) were significantly higher (p < 0.001 and p = 0.041, respectively) than those living in the rural district of Shijiazhuang (24.3 ng/ml). The young female sub-population had the lowest ΣPFAA concentrations compared with older females and all males. On average, the proportion of linear PFOS (n-PFOS) was only 48.1% of ∑PFOS, which is much lower than what was present in technical PFOS from the major historical manufacturer (ca. 70% linear), and which is also lower than data reported from any other countries. Moreover, the proportion of n-PFOS decreased significantly with increasing ∑PFOS concentration in the serum samples (r = − 0.694, p < 0.001). Taken together, the data lend weight to previous suggestions that i) high branched PFOS content in serum is a biomarker of exposure to PFOS-precursors, and ii) that people with the highest ∑PFOS concentrations are exposed disproportionately to high concentrations of PFOS-precursors. On average, linear PFOA (n-PFOA) contributed 96.1% of ∑PFOA, significantly higher than in technical PFOA (ca. 75–80% linear), but lower than in Americans, suggesting higher exposure to electrochemically fluorinated PFOA than in other countries, including the United States.

Introduction

Perfluoroalkyl acids (PFAAs) are a group of chemicals that have been widely used in many industrial and household commercial products for decades, and have been detected in people all over the world (Fromme et al., 2009, Kannan et al., 2004, Kato et al., 2011, Olsen et al., 2012, Pan et al., 2010, Zhang et al., 2010a). Perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) are the most common PFAAs found in humans (Fromme et al., 2009, Kannan et al., 2004, Kato et al., 2011, Olsen et al., 2012, Pan et al., 2010, Zhang et al., 2010a). Some studies show evidence that PFOS or PFOA are associated with negative health effects in humans, such as, on liver function (Gallo et al., 2012), chronic kidney disease (Shankar et al., 2011), later age of puberty (Lopez-Espinosa et al., 2011) and impaired response inhibition in children (Gump et al., 2011). Due to additional concerns about its environmental persistence, and potential to accumulate in foodwebs and in humans, PFOS was listed as a persistent organic pollutant in 2009 by the Stockholm Convention (Wang et al., 2009a).

Historically, two major manufacturing methods have been used to produce PFAAs and their precursors, namely electrochemical fluorination (ECF) and telomerization. The ECF method, which was used by 3M Co. to produce PFOA since 1947 and perfluorooctanesulfonyl derivatives (i.e. PFOS and its precursors) since 1949, leads to a complex mixture of linear and branched isomers in the final products (typically 70–80% linear, and 20–30% branched isomers) (Paul et al., 2009, Prevedouros et al., 2006). The telomerization method was developed by Dupont in the 1970s, and this produces isomerically pure products, typically of linear geometry (Kissa, 2005). After the voluntarily phase out of 3M ECF PFOA in 2002, telomerization became the dominant method for large-scale manufacturing of PFOA in the world (Prevedouros et al., 2006). Since the 3M Co., the largest manufacturer of PFOS, announced to phase out perfluorooctyl-based chemicals in 2000, global production volumes of PFOS initially declined (Paul et al., 2009). However, the manufacturing of perfluorinated chemicals in China has increased since 2002, and the production of PFOS increased up to the peak (246.88 t) in 2006 (Zhang et al., 2012). Moreover, the major manufacturing method(s) for other PFAAs in China, including PFOA, have not been reported to our knowledge. Nonetheless, it has been reported that PFOA, PFOS and PFOS-precursors (PreFOS) continue to be manufactured by the ECF process in Europe and Asia (Benskin et al., 2010a, Martin et al., 2010, Prevedouros et al., 2006, Zhang et al., 2012).

Pharmacokinetic studies in rodents, fish and chicken embryos have demonstrated that linear PFOS (n-PFOS) and linear PFOA (n-PFOA) are preferentially accumulated (Benskin et al., 2009a, De Silva et al., 2009a, De Silva et al., 2009b, O'Brien et al., 2010, Sharpe et al., 2010). In addition, it has been reported that the toxicity of PFAAs can also be isomer-specific. Loveless et al. (2006) found that n-PFOA was generally more toxic than a technical mixture of branched PFOA, whereas in cultured chicken embryonic hepatocytes technical PFOS (65% linear) elicited a greater transcriptional response than n-PFOS alone (O'Brien et al., 2011). It may therefore be assumed that the accumulation and toxicity of PFAAs for humans is also isomer-specific, but to date no isomer-specific data exists, perhaps owing to the fact that concentrated authentic standards are not yet available. It has also been suggested that the isomer patterns of PFAAs in humans may be important biomarkers of exposure source(s), including the manufacturing origin of the PFAAs (De Silva and Mabury, 2006).

There are only a few studies that have used isomer profiling of PFAAs in human samples as a means of assessing exposure source, and these are only for people in the U.S., Canada and Europe (Beesoon et al., 2011, Benskin et al., 2007, De Silva and Mabury, 2006, Kärrman et al., 2007, Riddell et al., 2009). A consistent result in all these studies is that relative to the known compositions of electrochemical technical products, n-PFOS is present in lower proportion, and n-PFOA present in higher proportion than expected, relative to the respective branched isomers of each. For PFOS, it has been suggested that increasing relative quantities of branched PFOS isomers is a biomarker of increasing relative exposure to PFOS-precursors (Martin et al., 2010, Ross et al., 2012, Wang et al., 2009b). For PFOA, it is thought that declining relative proportion n-PFOA is a biomarker of increased relative exposure to ECF PFOA (Benskin et al., 2010b, De Silva and Mabury, 2006). All data in these previous studies are from small sample populations, typically less than 25 people, and only the isomers of PFOA or PFOS were investigated. To our knowledge, there is no existing report of PFAA isomer profiling in people from China, and this is unfortunate because, unlike in North America, both PFOS and PFOA are still being manufactured and used in China. The isomeric profiling in Chinese people could be significantly different from in other populations. Such data may have toxicological relevance, but are also potentially useful for identifying sources of human exposure in China.

In this study, 129 serum samples were collected from two mid-scale industrial cities, Shijiazhuang and Handan, in North China. A previous study (Pan et al., 2010) reported that relatively high PFAAs were found in the people in this region. Twenty-one PFAAs (including PFOS and PFOA isomers) and perfluorooctane sulfonamide (PFOSA) were analyzed in these samples. The objectives were to quantify PFAAs and the isomer profiles of PFOS and PFOA in these Chinese people, to elucidate the impacts of gender and age on the isomer-specific accumulation pattern, and to try to evaluate the sources of PFOS and PFOA exposure in these populations.