Polyfluoroalkyl and perfluoroalkyl substances (PFAS) are large family of organofluorinated compounds that contain carbon chains with stable carbon-fluorine (C-F) bonds, and they have been gaining attention in recent years due to their toxicity. The PFAS family is estimated to exceed 4,000 synthetic fluorinated compounds (Bolan et al., 2021) with Perfluorooctanesulfonate (PFOS) and perfluorooctanoic acid (PFOA) being the most frequently encountered PFAS (Ateia et al., 2019; Singh et al., 2019; Cui et al., 2020; Stoiber et al., 2020). PFAS can be classified by their polar group, a group that gives PFAS high solubility in water and is non-volatile. PFAS contain at least one perfluoroalkyl moiety in the chemical structure, including groups of perfluorinated phosphonic acids (PFPA), perfluorinated carboxylic acids (PFCA) and perfluorinated carboxylic acids (PFCA), while polyfluorinated groups include sulfonic acids, fluorotelomers (FTS), polyfluorinated alkyl phosphates (PAP), fluorotelomer alcohols (FTOH), perfluorooctane sulfonamine (PFOSA) and their derivatives, Figure 1. Anionic PFAS with sulfonate or carboxylate polar groups are the group with the greatest focus from public and regulatory entities, however, PFAS with cationic and zwitterionic polar groups are also beginning to generate environmental concern.

They have a high thermal and chemical stability due to their carbon fluorine bonds and may possess hydrophobic or lipophobic moieties making them impermeable to water and oil and resistant to friction. Thanks to these advantageous properties, they have an extended life and durability (Lenka et al., 2021). PFAS have been widely used in industrial and commercial applications since the 1940s with some of their uses including fire-fighting foams as surfactants, waterproofing treatment for textiles, personal care products, cleaning products, food packaging, photos films, and many automotive, medical, and aerospace products.

Their strong C-F bonds, their possession of a fluoroalkyl tail, high chemical, and thermal stability, as well as their resistance to chemical and biological degradation also makes them hard to break down and extremely persistent in the environment (Ateia et al., 2019; Gagliano et al., 2020; Zhang et al., 2022). PFAS high persistence, widespread use and bioaccumulation potential has resulted in an environmental problem of high global concern, derived from the rapid distribution of these compounds in surface and groundwater, and many drinking water supplies in concentrations reported as highly toxic for different ecosystems and human health (Singh et al., 2019). The United States Environmental Protection Agency (EPA) recommends that PFOS and PFOA do not exceed 70 parts per trillion (70 ng L⁻¹), while the European Union introduced drinking water regulations at parts per billion levels (Gobelius et al., 2018). The monitoring of PFAS in the environment is essential to protect human health and safety. In recent years biotechnology has made exponential progress in the development of new technologies for PFAS sensors, allowing the effective in field monitoring at lower costs in comparison to standard technologies such as HPLC (Menger et al., 2021). Conventional wastewater treatment processes in wastewater treatment plants (WWTPs) are ineffective at degrading emerging pollutants such as PFAS, mainly due to their low concentrations and high hydrophilicity. The mostly commonly used processes are anaerobic or aerobic biological treatments only break carbon chains (C-C), producing short-chain PFAS. This often results in higher concentrations of PFAS in treated water than untreated water (Gagliano et al., 2020). PFAS are also resistant to other common WWTP processes such as ultraviolet radiation, disinfection with free chlorine, oxidation by ozone and hydroxyl free radicals. They show some degradation with advanced oxidation but often degrade into shorter chain PFAS (Nzeribe et al., 2019). Adsorption, high pressure nanofiltration and reverse osmosis membrane processes have shown substantial effectiveness in removing PFAS (Kucharzyk et al., 2017). However, there are other problems inherent to the removal of PFAS by the most advanced techniques, which are the influence of the water matrix and its frequent regeneration, and the removal of concentrates with a high content of PFAS (Gagliano et al., 2020).

The review highlights the environmental problem posed by PFAS, focusing on their sources, occurrence and transport in water, their negative effects on human health as well as in the environment, the most recent technologies for the detection and degradation of PFAS, as well as their regulations of use, release, and monitoring in the environment.

PFAS are a class of synthetic organic chemicals containing fluorinated carbon chains with different functional groups initially long chain and more recently, short chain PFAS have been developed (Kwiatkowski et al., 2020). Some of the functional groups include alcohols (-OH), amines (-NH₂), halogens (-F, -Cl, -Br, -I), esters (-CO₂R), ethers (-O-), thiols (-SH), carboxylic acids (-CO₂H), sulfonic acids (-SO₃H), sulfinic acids (-SO₂H), sulfones (-SO₂R), phosphate acids (-PO(OH)₂), phosphinic acids (-PO(OH)), polymers, salts and derivatives. In the past decade, the number of PFAS has increased considerably due to its extensive applications. From 2015 to 2018 the number increased from 3,000 to 4,700 registered PFAS (KemI, 2015; OECD, 2018). Most PFAS substances have only one identified application or have been patented for only one use. Many potential uses of different PFAS have not been explored yet. Contrary to single-use substances, some PFAS have many applications associated with them (Glüge et al., 2020). Figure 2 shows 12 PFAS that are assigned 10 or more uses.

The PFAS lifecycle consists of four steps: PFAS production, product manufacture, product use and waste management. In each step PFAS are released to the environment (Wahlström et al., 2021). Recent works have highlighted the mechanisms of environmental occurrence and transport by which they reach different water bodies causing pollution and health associated risks. PFAS reach most freshwater bodies, such as rivers, lakes and groundwater (Guelfo et al., 2018; Chambers et al., 2021).

The production of PFAS starts with the mining of Fluorspar. In 2017, 63% of this material was extracted from China and 26% from Mexico (Raichl and Schatz, 2019) causing associated problems elsewhere (Jha and Tripathi, 2021; Solanki et al., 2022). The mineral processing needed to generate PFAS is a Global Warming Potential and Ozone Depletion Potential as it emits unquantified amounts of halogenated substances into the environment. PFAS production generates monomers of volatile and ionic compounds which also generate unquantified emissions that contaminate environment surrounding the production facilities and affect local communities (Kwiatkowski et al., 2020; Wahlström et al., 2021). Some of the activities of production include tetrafluoroethylene synthesis, polymerization, initiators, solvents and carriers, dispersants, and chain transfer agents. Moreover, some PFAS form part of products such as coatings, textiles, biomedical utensils, implants and orthopedic devices, foams and additives. Once the products have been used, they generate waste and mainly make their way to landfills or get treated thermally, by wastewater treatment plants, and less often, by recycling (Wahlström et al., 2021).

Due to their characteristics, PFAS have been suitable for multiple applications such as fire-fighting foams, defoaming additives, adhesives, cosmetics, cleaners, coating, among others, due to their properties such as surface activity and repellence to water, oil, and stains (Guo et al., 2020). The concern about PFAS is associated with their persistence, bio accumulative potential, and possible adverse effects on human health which are difficult to determine due to the complexity of environmental exposure. Animal models do not always reflect human toxicokinetics accurately, in addition to the fact that exposure to PFAS often occurs from mixtures which might act synergistically. Public attention has increased in the last years, positioning perfluorooctane sulfonate (PFOS) and its precursors in the list of persistent organic pollutants (POPs) from the Stockholm convention in 2009 (Boone et al., 2019; Guo et al., 2020).

Studies have associated the presence of PFAS in water to specific sources and daily activities, such as fire training facilities (Ahrens et al., 2014), the textile industry, domestic sewage and household garbage (Guo et al., 2020), as shown in Table 1. The presence of these compounds in water even after regulation does not show significant changes. Furthermore, their persistence has been detected up to 60 km away from an associated source (Boiteux et al., 2017). There is an association between seasons and PFAS water concentrations, with an elevated PFAS concentration observed during summer, mainly attributed to droughts. Nevertheless, during a specific study by Chen et al. (2017) no clear association was made between seasons and PFAS concentrations in different points of a river. At some sampling points PFAS concentrations increase with water flow, in others the opposite effect was observed. A possible explanation for this can be the different contamination sources, while for some the source could constantly discharge some untreated wastewater with a high concentration of PFAS, in other cases the water flow could affect the dilution factor, and in other cases the contamination source could be PFAS accumulated in soil where water flow increases compounds dragged to the river (Chen et al., 2017).

Due to PFAS transport phenomena, Figure 3, the presence of these substances in soil poses a long-term threat to water sources. The migration of PFAS from soil to groundwater could take from 3 to 20 years depending on the transport phenomena (Brusseau and Guo, 2021). These results are interesting as they suggest that even if regulation decreases the amount of PFAS discharged, the actual accumulation of these substances in soil would still impact water quality over the next 20 years. The major problem with PFAS and their transport to water is that conventional drinking water treatments did not efficiently remove it. In fact, different studies have shown the persistence of different PFAS in water, reporting no significant difference in the concentration before and after the treatment, even finding that some advanced treatment as ozonation could increase PFAS concentrations (Boiteux et al., 2017; Boone et al., 2019).

PFAS persist in a variety of different matrices, increasing the possibility of interaction with humans. PFAS contact mainly derives from activities during their production or contact with their subproducts. Diverse studies demonstrate that regardless of if people have been directly exposed or not, most people end up with PFAS in their system (Kato et al., 2018; Calafat et al., 2019; Li et al., 2021; Peng et al., 2022). The United States developed the National Health and Nutrition Examination Survey (NHANES) in the early 2000’s which included information of the presence of PFAS paired samples in serum and urine in people above 6 years of age. The study found a presence of long chain PFAS in urine and short chain PFAS in serum. These findings were not associated to specific activities or a clear exposure to PFAS (Kato et al., 2018; Calafat et al., 2019). On the other hand, the association between demographic factors and PFAS exposure was assessed in waste recycling workers. The study found concentrations up to 66 ngL⁻¹ in urine samples and 33 ngL⁻¹ in serum (Peng et al., 2022). Finally, Li et al. (2021) associated the presence of PFAS not only to carrying out activities that favor contact with these substances, but also to environments where they had detected PFAS in air and drinking water samples. The study was carried out on children 4–6 years old and detected the presence of PFAS in hair and urine samples. These studies show that the correct management of PFAS and the development of technologies that allow for their removal are needed.

Due to their chemical nature, characterized by strong C-F bonds along their backbone, PFAS are highly resistant to thermal, and biochemical degradation which leads to their accumulation in the environment and in human tissues (Buck et al., 2011). The physicochemical properties of PFAS are strictly related to the size of the chain and functional groups, resulting in two theories about their bioaccumulation and/or biomagnification mechanisms: PFAS bind to proteins such as serum albumin, fatty acid binding proteins and organic anion carriers; PFAS are divided into membrane phospholipids due to their greater affinity to charged species, which could result in greater bioaccumulation and distribution, as well as greater difficulty in elimination (Chen et al., 2021). The main way of exposure to PFAS is through polluted drinking water or food, which could be contaminated by cookware, food packing or from remnant sources of PFAS in the environment (Domingo and Nadal, 2019). Although there is still controversy about the degree of toxicity in the human body, several PFAS have been associated to diabetes, obesity, high cholesterol, certain types of cancer, and some effects during pregnancy such as neurodevelopment, and immunomodulation (Corsini et al., 2014; Sunderland et al., 2019). Figure 4 remarks the principal effects on human health.

Since their implementation was suspended in the early 2000s, the toxicity of PFAS has been rigorously tested. The U.S. Department of Health and Human Services, through the National Toxicology Program, has issued a series of technical reports about the toxicological effects caused by chronic exposure to perfluorinated sulfonated and carboxylated substances in rodents (National Toxicology Program (NTP), 2020). The results showed that the exposure to perfluorooctanoic acid (PFOA) has been associated with toxicity in liver, kidney, and thyroid gland, and with certain cancerogenic activity. After gavage administration the time of PFAS clearance increases with chain length (Huang et al., 2019a) from a half-life time of a few hours for perfluorobutane sulfonate (PFBS) to nearly 20 days for perfluorooctane sulfonate (PFOS), which increases their toxicity. Similar analyses were performed, with similar results, for 8:2 fluorotelomer alcohol (8:2-FTOH), perfluorohexane-1 sulfonic acid (PFHxS), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), and perfluorodecanoic acid (PFDA)) (Huang et al., 2019a, 2019b; Dzierlenga et al., 2020). Toxicity studies of perfluorobutane sulfonic acid, perfluorohexane sulfonate potassium salt, perfluorooctane sulfonic acid, perfluorohexanoic acid, perfluorononanoic acid, and perfluorodecanoic acid have also been performed (National Toxicology Program (NTP), 2021a; National Toxicology Program (NTP), 2021b).

Several PFAS act as endocrine disrupting chemicals, increasing the risk of neurodevelopmental disorders, and obesity (Braun, 2017). PFOA and PFOS promote the activity of peroxisome proliferator-activated receptor-α (PPARα), and -γ (PPARγ) in humans, mice, and rats (vanden Heuvel et al., 2006). This impairment in PPARα activity affects adipocytic differentiation, increasing body fat, and the immunotoxicity of PFOA, presumably through modifications in antibody production (Bastos Sales et al., 2013; Corsini et al., 2014; Sunderland et al., 2019). PPARα impairment directly alters the cytokine production and human immune cell activation, throughout the inhibition of NF-κB activity. PFOA and PFOS toxicity reduces p65 phosphorylation which is crucial for the genetic transcription induced by NF-κB (Corsini et al., 2011, 2012).

It is still too soon to understand the effects of PFAS exposition completely. PFAS can also promote hepatocyte necrosis, hepatomegaly, splenic atrophy (Frawley et al., 2018), and interfere with mitochondrial respiration (Wallace et al., 2013). Some PFAs move evenly across the placental passage which exposes the fetus to PFAS (Gützkow et al., 2012). Maternal exposition to PFOS, PFOA and PFNA have been associated to lower birth weight (Verner et al., 2015), an impaired immune response in early childhood (Pennings et al., 2016), the risk of miscarriage and preeclampsia (Gao et al., 2021).

The findings of PFAS exposure during pregnancy have been inconsistent. Gao et al. (2021) carried out a statistical study of recent reports where the direct link between the effects of PFAS in pregnancy at concentrations greater than 1 ng/ml, showing that exposure to PFOS was directly associated with the risk of premature birth, exposure to PFNA and PFOA showed a relationship in the inverted U-shaped with risk of preterm birth, and exposure to PFDA and PFOS were directly associated with risks of miscarriage and preeclampsia, respectively. In vitro and in vivo studies have shown that exposure to PFAS has negative effects essential biological processes of the ovary, such as folliculogenesis and steroidogenesis which are the development of oocytes and follicles, as well as the consequent decrease in ovarian reserve, which are also linked to irregular and longer menstrual cycles, late menarche, and early menopause. These effects are associated with some alterations such as the activation of the peroxisome proliferator-activated receptor (PPAR), oxidative stress, interruption of thyroid hormone and interruption of gap junction intercellular communication. These studies were limited to ranges of human exposure to PFAS, PFOA from 3 to 220 ng/kg and PFOS from 1 to 130 ng/kg of body weight (Ding et al., 2020).

Grandjean et al. (2012) studied the effect of PFAS on the production of antibodies in children after the tetanus and diphtheria vaccines. The doubling of serum concentrations of PFAS such as PFOA, PFOS and PFHxS in children aged 5, led to a 50% loss of serum antibody concentrations by the time the children turned 7 years old.

PFAS exposition is not only a problem for human health. Poly- and per-fluorinated substances have are of great concern to the environment too. Several PFAS have been detected in many organisms across the globe and their toxic response varies in a species dependent manner (Fitzgerald et al., 2019; Hitchcock et al., 2019; Niu et al., 2019; Gaballah et al., 2020; Abercrombie et al., 2021; Ask et al., 2021; Death et al., 2021; Liu et al., 2022). Ankley et al. (2021) made an exhaustive revision of the myriad of PFAS-induced alterations on relevant members of animalia kingdom such as invertebrates, fish, amphibians, birds, reptiles, and mammalian wildlife. Invertebrate organisms only have an innate immune system that is based on protection by hemocytes or coelomocytes, which have an important role in non-specific cellular immunity, which, contrary to vertebrate organisms, have an adaptive immune system that offers them greater protection. Several PFAS have been shown to have negative effects on the cell viability of the innate immune system of earthworms, bivalves, and crustaceans (Ankley et al., 2021).

An extensive study on the effect of PFAS on zebrafish included the in vivo analysis of 139 PFAS at 10 concentrations in water between 0.015 and 100 µM from 6 to 120 h after fertilization, analyzing the larval photomotor response (LPR), the embryonic photomotor response (EPR) and 13 morphological endpoints as study response variables. The study showed that 49 PFAS exhibited bioactivity in one or more assays, with 25 induced altered LPR, 11 altered EPR, and 31 altered morphologies. Perfluorooctanesulfonamide (FOSA) was the only substance with activity in the 3 assays and perfluorodecanoic acid (PFDA) was the one that showed the highest bioactivity (Truong et al., 2022).

Similarly, the study carried out by Rericha et al. (2021) showed that 21 PFAS out of 58 studied induced aberrant larval behavior in zebrafish, without significant mortality. Already in larval development studies with concentrations of 0–100 μM of different PFCA with chain sizes between 4 and 12 carbons, they demonstrated an abnormal LPR, without significant alterations of the EPR or significant mortality.

The bioassay on the effect of PFOA and PFOS on Daphnia carinata carried out by Logeshwaran et al. (2021) demonstrated an LD50 at 48 h of 78.2 (54.9–105) mg L⁻¹and 8.8 (6.4–11.6) mg L⁻¹, respectively. Chronic exposure for 21 days showed effects on reproduction, with an increase in days to generate the first offspring and a reduction in the number of offspring and an increase in offspring mortality at concentrations from 0.001 mg L⁻¹. The genotoxicity study using the comet assay at concentrations of 1–10 g L⁻¹ showed significant damage to the genetic composition of D. carinata.

This environmental crisis urges the development of public policies, methodologies and technologies focused on the proper management and disposal of these highly durable substances that are having a great impact on ecosystems and human health. Despite the existence of several data regarding the neurotoxicity and its effects of PFAS, there is still a lack of research and development of new tests to evaluate all the possible effects of PFAS.

As the detection methods show, the concentration of PFAS in the environment has increased with the human activities. One common migration pathway of the contaminants to the environment is through the sewage, as most of the WWTPs are not capable of removing efficiently PFAS. Traditional WWTPs have primary and secondary treatments focused on the removal of solids and disinfection to eliminate biological pathogens, and in some cases a tertiary treatment for the removal of other contaminants (Rout et al., 2021). However, persistent contaminants like PFAS are not efficiently removed during these treatments (Lenka et al., 2021).

In this way several approaches have been evaluated to reduce the leakage of these contaminants to the environment. Nevertheless, some of the technologies employed with other contaminants, like chlorination, flocculation or precipitation, may produce toxic by-products or are less efficient with PFAS (Mazhar et al., 2020; McCord et al., 2020; Rout et al., 2021). Due to this, most of the studies have been focused on the application of adsorption, advanced filtration, advanced oxidation and biodegradation processes (Phong Vo et al., 2020).

Nevertheless, the high harmful impacts of PFAS on human health, the international treaties to reduce the production of PFAS were signed in the early 2000 s. The implemented regulations have specific restrictions based on national, state and territory-level, even though there are differences within countries. The US EPA released limits for the use of PFOS and PFOA in 2016. After that, a rapid increase in the number of states following the policies to prevent the PFAS pollution and their effects (Brennan, et al., 2021).

Some PFAS have been regulated in Europe. PFOA and PFOS and another long chain (PFHxS) were listed in the Stockholm Convention on Persistent Organic Pollutants (POPs) and restricted under the EU. Alternatives were developed to substitute long-chain PFAS, however they still trigger adverse effects in human health and the environment. Due to these concerns the short-chains PFAS are starting to be regulated under EU (European Commission, 2020).

The PFOA regulations in Asian countries are moving to strengthen the decision of the use of chemical substances. In April 2021, PFOA was added to the list of Chemical Substances Control Act, but related substances are excluded from that. Also, PFOA use was restricted in China in 2020. Other countries such as Taiwan and Singapore the use of PFOA is partially regulated (Enviliance ASIA, 2021).

Challenges derived from PFAS are complex, making it difficult to develop policies. The lack of funding supporting PFAS legislation, the variable monitoring of their impact on the environmental and human health worldwide, the limited release of scientific evidence, and restricted cultural understanding of the prioritization of environmental issues. Furthermore, substitutes need to keep their advantageous properties while avoiding their negative properties in order to propel their widespread adoption.

PFAS are very stable chemical substances of low biodegradability that do not hydrolyze or photolyze under ambient conditions, resulting in persistent and bioaccumulative substances in the environment that are extremely difficult to remedy. The wide distribution in aquatic environments derived from its physicochemical properties and high solubility in water, which have generated concern about possible negative effects on human and animal health. The increasing concentration of PFAS in the environment, especially in water, has become an important problem gaining the scientific communities’ attention particularly with a focus on the detection and removal of these contaminants.

The study of the distribution and ecological risks of PFAS in the environment is a multidisciplinary challenge that requires collaboration between experts from many areas from the field of chemistry, biotechnology, environmental toxicology, health, among many others to solve lack of information and problems associated with the distribution of PFAS. The PFAS family is made up of chemical compounds with highly variable physicochemical properties, which depending on the destination or exposure to these compounds, their effects may vary.

The real time analysis of influents and effluents of WWTPs is needed to ensure the quality of the water treatment to avoid the discharge of PFAS back to the environment. This will be a challenge, particularly when coupled with traditional detection methods. In this way, spectroscopic methods for detection are a promising alternative that requires more attention to go beyond the proof-of-concept stage.

Regarding the removal technologies, membrane technologies have shown high efficiency of removal compared to other methods, however their operational costs hinder their applications in most WWTPs, making technologies like RO more suitable for its application in drinking water treatment. Due to this, adsorption and advanced oxidation processes represent an attractive alternative for wastewater treatment, especially for their implementation in developing countries. Adsorption has already showed high potential in the removal of several emerging contaminants, mainly due to the wide variety of adsorbents, its relative low cost, ease of operation and competitive removal rates. However, for its application for PFASs removal it is necessary further research to understand better the adsorption mechanisms and to improve the selectivity, the major challenges of this technology. On the other hand, diverse AOPs have been already tested at pilot scale with good PFASs removal rate, being photocatalytic degradation and Fenton-based the ones with better results. Despite the great performance of AOPs, it is necessary to improve their energetic efficiency and selectivity for being applied in real urban and industrial effluents.

As knowledge of the different types and physicochemical behavior of PFAS grows, more efficient and economic strategies as well as technologies for detection and degradation are created. These advances aim to fulfill current global regulations as well as inspire new ones to control the excessive use of products with PFAS as well as generate public knowledge about PFAS environmental and human health impact.

Current reports on the study of PFAS continue to generate new information on damage to health and the environment, however, more information on compounds as well as their combinations are needed, as it difficult to obtain all information on each PFAS. In recent years, different effective bio-based technologies have been developed that remove PFAS. As they because they still lack information regarding efficacy in complex samples, different WWTP flows, and generation studies. degradation compounds and their effects approval and implementation. Some effective actions to manage the risks surrounding PFAS and their continuous accumulation in the environment would be to regulate the production and use of these compounds, emphasizing the importance of eliminating non-essential uses of PFAS, as well as developing of biodegradable compounds with similar properties, as well as the continuous study of strategies and technologies for the detection and safe elimination of PFAS in the environment.