Rational
Per- and polyfluoroalkyl substances (PFAS, also spelled PFASs) are a group of 5,000 to 10,000 organic chemicals commonly used in numerous industrial and commercial applications worldwide [1]. PFAS are exclusively synthetic, and thus do not naturally occur in the environment [2]. They are water and oil repellent and have a high persistence. These chemical properties have made them favourable additives to many different products and industrial applications. Some of the best-known and widely distributed of those are the fluoropolymer Teflon, the stain-resistant coating Scotchguard and aqueous film-forming foam (AFFF) [2–5]. One of the downsides of PFAS is their extreme persistence, high mobility, and ubiquitous distribution throughout the environment. PFAS accumulate in the environment and bind to human and animal blood proteins [6–9]. Some studies have also presented evidence for a link between PFAS exposure and health effects in humans [10] and wildlife [11, 12].
PFAS include per- and polyfluoroalkyl substances. In perfluoroalkyl acids (PFAA), every hydrogen atom on the carbon chain has been replaced by fluorine, whereas in the polyfluoroalkyl acids this is not the case, as only some hydrogen atoms have been replaced here.
PFAS can be divided into long-chain and short-chain substances. Perfluoroalkyl carboxylic acids (PFCA) – with seven or more fully fluorinated carbon atoms (CnF2n + 1COOH; n ≥ 7; e.g., PFOA) – and perfluoroalkane sulfonic acids (PFSA) – with six or more (CnF2n + 1SO3H; n ≥ 6; e.g., PFHxS) – are considered long-chain PFAS and tend to accumulate in biota and the environment more than their short-chain counterparts (see Table 1 for a list and abbreviations of common PFAS) [13–15]. In addition, PFSAs accumulate to a larger extent than PFCAs of the same perfluoroalkyl chain length. This is thought to be due to their ability to bind to serum proteins more strongly [16, 17].
Table 1
Types of PFAS included in the systematic map. PFAS are listed in their acidic form.
Name of PFAs group | Abbreviation | Full name | CAS Registry No. |
Perfluoroalkyl carboxylic acids (PFCA) | PFBA | Perfluorobutanoic/ perfluorobutyric acid | 375-22-4 |
| PFPeA | Perfluoro-n-pentanoic acid | 2706-90-3 |
| PFHxA | Perfluorohexanoic acid | 307-24-4 |
| PFHpA | Perfluoroheptanoic acid | 375-85-9 |
| PFOA | Perfluorooctanoic acid | 335-67-1 Perfluorooctanoic acid 95 % | 335-67-1 Perfluorooctanoic acid 95 % | 335-67-1 |
| PFNA | Perfluorononanoic acid | 375-95-1 |
| PFDA/ PFDeA/ PFDcA | Perfluorodecanoic acid | 335-76-2 |
| PFUnDA/PFUnA/ PFUA/ PFUdA | Perfluoroundecanoic acid | 2058-94-8 |
| PFDoA/PFDoDA | Perfluorododecanoic acid | 307-55-1 |
| PFTrDA/ PFTriDA/ PFTrA | Perfluorotridecanoic acid | 72629-94-8 |
| PFTA/ PFTeDA | Perfluorotetradecanoic acid | 376-06-7 |
Perfluoroalkane sulfonic acids (PFSA) | PFBS/ PFBuS | Perfluorobutane sulfonic acid | 375-73-5 |
| PFPeS | Perfluoropentane sulfonic acid | 2706-91-4 |
| PFHxS | Perfluorohexane sulfonic acid | 355-46-4 |
| PFHpS | Perfluoroheptane sulfonic acid | 375-92-8 |
| PFOS | Perfluorooctane sulfonic acid | 1763-23-1 |
| PFNS | Perfluorononane sulfonic acid | 68259-12-1 |
| PFDS | Perfluorodecane sulfonic acid | 335-77-3 |
| PFECHS | Perfluoroethylcyclohexane sulfonic acid | 335-24-0 |
Polyfluoroalkyl substances derivates | ADONA | 4,8-dioxa-3H-perfluorononanoic acid | 958445-44-8 |
Perfluoroalkyl ether sulfonic acids | 6:2Cl-PFESA (F-53B) | 6:2 Chlorinated polyfluoroalkyl ether sulfonate | 73606-19-6 |
| 8:2 Cl-PFESA | 8:2 Chlorinated polyfluorinated ether sulfonate | 83329-89-9 |
| Nafion BP2 | Nafion Byproduct 2 | 749836-20-2 |
Fluorinated polymers | Hydro-Eve | 2,2,3,3-Tetrafluoro-3-((1,1,1,2,3,3-hexafluoro-3-(1,2,2,2-tetrafluoroethoxy)propan-2-yl)oxy) propanoic acid | 773804-62-9 |
Perfluoroether alkane carboxylic acids | PFO4DA | Perfluoro-3,5,7,9-tetraoxadecanoic acid | 39492-90-5 |
| PFO5DoDA | Perfluoro-3,5,7,9,11-pentaoxadodecanoic acid | 39492-91-6 |
| HFPO-DA (GenX) | Hexafluoropropylene Oxide (HFPO) Dimer Acid | 13252–13–6 |
| HFPO-TA | Hexafluoropropylene Oxide (HFPO) Trimer Acid | 13252-14-7 |
Fluorotelomer Sulfonates (FTSs) | 6:2 FTS/FTSA | h,1 h,2h,2 h-Perfluorooctane sulfonic acid | 27619-97-2 |
| 8:2 FTS/FTSA | 2-(Perfluorooctyl)ethane-1-sulfonic acid | 39108-34-4 |
While the US-based company DuPont accidentally developed the first PFAS compound in 1938 (Lyons 1994), the company 3M, also US-based, grew into the biggest PFAS producer worldwide and started the commercial manufacturing process of PFOA, PFOS and many other PFAS in the 1950s [19]. Since then, PFOS and PFOA have become the most produced, distributed and researched members of the PFAS family [20, 21]. One of the main applications of PFAS is in AFFF products which included a wide range of different PFAS as active ingredients including PFOS, PFOA, and PFHxS. Due to the effectiveness of AFFF products in controlling hydrocarbon fires, these products have been broadly deployed for training or disaster management across military sites, civilian airports and firefighting training centres since the 1970s [22]. In the 1980s, China joined the growing number of PFAS-producing countries [23, 24]. Thus, as early as 1968 research suggested that PFAS accumulated in the human bloodstream [25]. Ubel et al. [26], Belisle [27], and Yamamoto et al. [28] eventually confirmed Taves’ [25] suspicion. Nevertheless, it took until the early 2000s before a large number of studies left no doubt that PFAS had not only made it into the human body, but also into wildlife [6], the oceans [29], and drinking water [30]. The unique chemical properties of PFAS prevented an earlier detection in the environment, as measurements required specific and particularly sensitive analytical methods that were beyond the capabilities of most laboratories until recent times [6].
In the early 2000s, it also became evident that PFAS had indeed a compromising effect on human and animal health [31, 32]. In the light of such findings, in 2002, the company 3M voluntarily phased out most of its production of long-chain PFAS substances, including PFHxS, PFOS, PFOA and FOSA [33]. As the demand for PFAS still existed, countries like China, Russia and India increased their production [34], whereupon the OECD [35] hypothesized that these countries’ PFAS production might have offset the phase out by 3M. In addition, the worldwide production of other PFAS, like PFUnDA, that were of lesser public concern, increased [36]. 3M and DuPont introduced PFBS and GenX as two new short-chain PFAS to replace PFOA [37] and PFOS [38], in 2003 and in 2009, respectively. In the meantime, national and international initiatives began attempts to restrict production and use of the most common long-chain PFAS. Among the most extensive programmes was the 2010/2015 PFOA Stewardship Program, initiated by the US Environmental Protection Agency in 2006, that aimed to eliminate PFOA emissions and production by the eight leading US manufacturers by 2015 [39]. Furthermore, the UN Stockholm Convention on Persistent Organic Pollutants (POPs) was signed by 152 countries in 2000, and vowed to strictly limit the use of PFOS to certain purposes [33]. However, the list of these exempted purposes included most of the common usages, such as photoimaging, firefighting foams, insect baits, metal plating and surface treatment of leather [33]. Moreover, the speed of the implementation of the Stockholm Convention differed significantly across countries. In 2017, China was the only known producer of PFOS, despite having ratified the Stockholm Convention [23]. While PFHxS is currently under review, PFOA was added to the convention as a harmful environmental pollutant to be eliminated by 2019 [23]. Figure 1 shows a short timeline of important events in PFAS-related history of production, use and legal restrictions, since the discovery of these chemicals.
After all, PFAS substances have truly earned their infamous reputation as ‘forever chemicals’. However, questions remain as to whether conventions and restrictions are actually reducing PFAS burdens in the humans, animals and the environment, and if so, when this effect will become apparent. In 2018, the UN Environment Programme declared PFOS, PFOA, PFHxS and PFNA as the most frequently detected PFAS worldwide [40]. In the same year, Land et al. [41] published a large systematic review on PFAS concentrations in humans and showed that exposures to PFOS, PFOA and PFHxS, were in decline in North America and Europe, potentially reflecting the impacts of legislated restrictions towards some types of PFAS. On the other hand, in China people are increasingly exposed to PFAS, like PFOS and PFOA, which was presumably due to the recent local peak in production [42]. However, PFAS contamination trends affect not only humans, but also non-human biota. Wildlife is constantly exposed to contaminants in the natural environment. Thus, PFAS burdens in wildlife are expected to reflect those of their habitat, however there is some uncertainty in these patterns (compared to patterns in humans). Depending on the geographical region and species, longitudinal studies have provided conflicting reports on trends in PFAS abundance in wildlife and the natural environment over the past 20 years [43–45].
PFAS concentrations in wildlife are also relevant in other ways than just reflecting the contamination of our natural environment. Many wildlife species, particularly fish, are an essential part of the diet of people in many different cultures [46]. The assessment of PFAS concentrations in such species is therefore of relevance to public health. Finally, assessing PFAS burdens in wildlife also serves the purpose of conservation management, especially for those species that have already been impacted by anthropogenic threats, such as loss of habitat and climate change. Exposure to ubiquitous PFAS in the environment could be another potential driver of population decline and extinction [11, 12].