FOCUS ON Per-and Poly-Fluoroalkyl Substances (PFAS)

The concentrations of per- and polyfluoroalkyl substances (PFAS) were determined in raw influent, final effluent, and treated biosolids at Canadian wastewater treatment plants (WWTPs) to evaluate the fate of PFAS through liquid and solids trains of typical treatment process types used in Canada and to assess time trends of PFAS in wastewater between 2009 and 2021. Data for 42 PFAS in samples collected from 27 WWTP across Canada were used to assess current concentrations and 48 WWTPs were included in the time trends analysis. Although regulated and phased-out of production by industry since the early 2000s and late 2000s/early2010s, respectively, perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and other long-chain PFAS continue to be widely detected in Canadian wastewater and biosolids. Short-chain PFAS that are not currently regulated in Canada were also widely detected. In general, elevated concentrations of several PFAS were observed at WWTPs that receive landfill leachate. Except for PFOS, concentrations of long-chain perfluoroalkyl carboxylates (PFCAs) and perfluoroalkane sulfonates (PFSAs) generally decreased over time in influent, effluent, and biosolids, which is attributable to industrial production phase-outs and regulations. Concentrations of PFOS did not decrease over time in wastewater media. This indicates that regulatory action and industrial phase-outs of PFOS are slow to be reflected in wastewater. Concentrations of short-chain PFCAs in wastewater influent and effluent consistently increased between 2009 and 2021, which reflect the use of short-chain PFAS as replacements for phased-out and regulated longer-chained PFAS. Short-chain PFAS were infrequently detected in biosolids. Continued periodic monitoring of PFAS in wastewater matrices in Canada and throughout the world is recommended to track the effectiveness of regulatory actions, particularly activities to address the broad class of PFAS.

Introduction PFAS (per-and poly-fluoroalkyl substances) are a group of human-made chemicals that have been used in a wide variety of industrial and consumer products since the 1940s. However, interest and scientific understanding of how they behave in the environment and their potential human health effects has been increasing more recently and is now a rapidly evolving area. This Focus On does not provide a comprehensive review of PFAS, but rather a general overview to support public health practitioners. This document summarizes the following:  general description, known sources and concentrations in the environment,  exposures,  potential health effects,  actions that can be taken to reduce exposures, and  current regulations in Ontario and Canada.

Methods
A rapid grey literature search of public health, environmental health and toxicology resources was conducted to identify information on PFAS, environmental sources, how individuals are exposed to PFAS, how their use is regulated in Canada and Ontario, and practical advice for reducing exposures. Information was generally sourced from reviews of PFAS from regulatory authorities.
A peer-reviewed published literature search was also conducted to obtain recent evidence summaries on human health effects associated with PFAS. Specifically, PHO Library Services conducted a search on September 1, 2022 for systematic reviews and meta-analyses in the Embase and MEDLINE databases on articles related to PFAS and human health. The library search excluded animal studies and limited results to English language articles published between 2012 and 2022, with results screened to identify systematic reviews and meta-analyses published in the last two years. The full library search strategy is available upon request.
What are PFAS?
PFAS are a group of synthetic chemicals with unique chemical properties such as resistance to extreme temperatures, resistance to breakdown/degradation, water and oil repellency and non-stick characteristics. [1][2][3][4] These unique properties resulted in their widespread use in a variety of industry and consumer products since the 1940s. There are thousands of PFAS chemicals which can be found in paper and cardboard coatings, leather products, stain-resistant carpet, upholstery, clothing, non-stick coatings on cookware, food packaging, paints, varnishes, sealants, cleaning products, personal care products and cosmetics, aqueous film-forming foam (AFFF) for fire-fighting, and in the production of electronics, plastics and metals. 1,2,[4][5][6][7][8][9][10][11]

PFAS IN THE ENVIRONMENT
Given their widespread use and chemical stability, PFAS have been widely detected in the environment. Major sources of PFAS in the environment include household waste (e.g., landfills), industrial sites where PFAS containing materials have been produced or applied, as well as AFFF firefighting events and training sites. [23][24][25] These sources contribute PFAS to soil, air and water by leaching into groundwater, discharging to surface water, as well as releases to air and soil through spills and emissions. Once released into the environment, PFAS can remain for prolonged periods either within the water table or partitioning into sediment with a fraction of AFFF becoming airborne during fires as aerosols and diffuse chemicals. 23,25 PFAS persist in the environment and the body relatively unchanged due to their chemical structures. 1,[3][4][5]7 PFAS are unlikely to degrade or transform under ambient environmental conditions, but laboratory experiments have demonstrated that some physical, chemical and biological processes can change the chemical structure of PFAS under specific conditions. These transformations can result in changes in the form of PFAS within a mixture (e.g. alcohol to aldehyde), or the size of the molecules, potentially changing the toxicity of original mixture. 24,25 At this time, limited Canadian data with varying trends are available on PFAS concentrations in environmental media. According to Environment and Climate Change Canada, PFOS concentrations in fish (lake trout) showed an overall increase from 1979 to 2000, concentrations then stabilized for a few years before beginning to decrease. 26 This is consistent with a 2022 study that showed that Canadian freshwater concentrations of legacy PFAS (PFOS and PFOA) decreased between 2013 to 2020, while the concentration of other PFAS substances such as perfluoropentanoic acid (PFPeA) and PFBA increased during that timeframe (possibly due to their use as replacement PFAS in consumer products in lieu of PFOS and PFOA). 27 However, trends in specific environmental media and by PFAS chemical may vary, as shown by Gewurtz et al. for certain wildlife, sediment and water samples collected in and around Lake Ontario between the late 1970s and late 2000s. 28 In general, there is not enough information to predict PFAS trends in concentrations for water, sediment and air, but environmental concentrations, combined with PFAS stability and persistence, can result in bioaccumulation and biomagnification in the ecosystem.

PFAS EXPOSURES
All Canadians are exposed to some PFAS due to their persistence in the environment. Exposure to PFAS can occur through food and consumer products, soil, indoor dust and drinking water. 4,9,10,20,29,30 PFAS exposure from drinking water may increase if consuming contaminated drinking water. 10,20,29 The primary route of exposure may also be age-dependent, with oral exposure (via hand-to-mouth activity) to consumer products (e.g., treated fabrics and carpets) as the primary route of exposure for infants, toddlers and children. 4,10,30

Dietary (Food and Water)
Diet is one way Canadians are exposed to PFOA, PFOS and other PFAS. 3,15,31,32 Food can become contaminated through the growing environment or processing equipment, through animal feed or water, or from food packaging material. 33 PFAS contamination in the growing environment does not necessarily indicate the grown foods will contain detectable levels of PFAS, as this will depend on the amount of PFAS in the growing environment, the type of PFAS present and the type of food/plant species. 33,34 In general, most foods not grown or produced in specific areas with known PFAS contamination do not have detectable levels of PFAS. 34 An analysis of food samples collected between 1992 to 2004 conducted by Tittlemier et al. estimated an average daily dietary exposure of 250 ng/day using a subset of samples collected as part of the Canadian Total Diet Study. 35 More recent data on PFAS levels in Canadian food are not available, but an ongoing dietary exposure assessment study conducted by the US FDA shows that the majority of food samples analyzed since 2019 do not have measurable concentrations of PFAS. 36 PFAS have been used in non-stick cookware and in food packaging materials (e.g., fast-food wrappers, microwave popcorn bags, and paperboard take-out containers such as pizza boxes). 21 However, the US FDA indicates the non-stick coating on cookware contains a negligible amount of PFAS capable of migrating into food and Health Canada's Food Research Division found food packaging was not a significant source of PFOA and PFOS. 21,37 Using an estimated average adult intake rate of 1.4 L/day, Tittlemier et al. (2007) used mean tap water concentrations from Calgary and Vancouver from another study to estimate 0.3 ng/day exposure to total PFAS via drinking water for the general Canadian population. 31,35 A more recent analysis of 226 treated drinking water samples provides drinking water concentrations from 25 drinking water systems in Ontario using river, lake and groundwater sources between 2012 and 2016. 38 Mean and maximum concentrations of a group of ten PFAS were 6.1 ng/L and 20.0 ng/L, respectively. Detection of individual PFAS chemicals was variable, with percent detection ranging from 0 to 73%. Drinking water exposures can be higher in areas where water with elevated PFAS concentrations is relied upon as a drinking water source. Exposures from water during common household activities such as bathing, showering, washing dishes, brushing teeth and laundry are expected to be negligible. 20,29,39 According to the United States Centers for Disease Control and Prevention (CDC) and the Agency for Toxic Substances and Disease Registry (ATSDR), PFAS can be found in breast milk and the level of exposure to an infant through breastfeeding depends on a number of factors (e.g., level of PFAS in the mother, the amount of PFAS that transfers through milk, the duration of breastfeeding). 5,10,30,40,41 A 2022 study of 664 Canadian breast milk samples found that total PFAS concentrations (sum of seven PFAS) ranged from 3.1 to 603 ng/L, with a median concentration of 106 ng/L. 42 PFOA was the most frequently detected compound and generally contributed the most to the measured PFAS concentrations (approximately 30%). 42 While further research on this potential route of exposure is needed, the CDC/ATSDR and the American Academy of Pediatrics state the benefits of breastfeeding outweigh any potential risks of PFAS exposure through breast milk. 40

Other
Other potential routes of exposure may include the ingestion of contaminated soil or household dust as well as the inhalation of aerosolized water. 10,30,[43][44][45] However, Health Canada reports that PFAS remain in water, they do not preferentially partition to air (i.e., it does not volatilize) and the primary mechanism for exposure to PFAS in drinking water is via ingestion. 20,29,39 While Health Canada and the United States Environmental Protection Agency (US EPA) recognize that exposures to PFAS by inhaling water aerosols contaminated with PFAS can occur, the total mass of aerosolized water is low and due to its low volatility, PFAS will not concentrate in air, making this route of exposure negligible. 20,29,43 PFAS exposure can also come from use of consumer products such as personal care products, leather products, carpets, upholstery and clothing. 9,10,46,47

PFAS LEVELS IN THE HUMAN BODY
Population-based biomonitoring data for select PFAS concentrations in human blood plasma are available via the Canadian Health Measures Survey (CHMS). Table 1 summarizes PFAS biomonitoring data from the most recent round of survey data (Cycle 6, 2018-2019) for the Canadian population aged 3-79 years. 46 Complete CHMS biomonitoring results by age group, sex and survey cycle are also available online. Human Health Effects Health Canada reports some PFAS are well absorbed in the body, poorly excreted and not extensively metabolized. 3,4 The potential health risks from exposure to PFAS depends on the level and duration of exposure (i.e., how much and for how long). 39 Toxicological studies involving laboratory animals have found high levels of PFAS are associated with reproductive, developmental, endocrine, liver, kidney and immunological effects. 3,10,50 However, effects observed in animals do not necessarily translate to humans.
The majority of systematic reviews and meta-analyses focused on epidemiological (human) studies published in the last two years have examined human health effects associated with exposure to PFOS and PFOA. As a result, the strength of the evidence for health effects is highest for PFOS and PFOA, as few studies have considered other types of PFAS.
Overall, epidemiological data from cross-sectional studies demonstrate sufficient evidence that elevated exposures to certain PFAS, particularly PFOS and PFOA are associated with increased liver enzymes which may indicate the presence of liver disease or damage. 51 There is also limited evidence that elevated exposures to certain PFAS are associated with increased risk of select adverse pregnancy outcomes including low birthweight and preterm birth; 52-55 kidney and testicular cancer (particularly with high exposure to PFOA); 56,57 and allergic outcomes in children including exposure to PFOS and atopic dermatitis, and exposure to PFOA and allergic rhinitis. 58 There is limited evidence that PFAS is associated with decreased immune response to diphtheria, tetanus, measles, mumps, and influenza vaccines based on a recent systematic review and meta-analysis. 59 Studies do not consistently show an association between PFAS and other pregnancy outcomes including small for gestational age, 52,55,59 miscarriage, 53-55 pregnancy induced hypertension, 55 as well as reproductive hormones (e.g., testosterone, estradiol) 60 and prostate cancer. 57 Overall, the clinical significance of the epidemiologic findings need further study.
Based on the evidence associated with PFAS exposure, agencies such as the ATSDR and Health Canada have identified that individuals with pre-existing conditions affecting the same systems (e.g., those with compromised liver function or immune systems), pregnant women and young children may be at a higher risk of health effects. 10,31,32 Our literature search did not identify systematic reviews or meta-analyses that examined the relationship between potential human health effects and PFAS mixtures. The gap in scientific research on how PFAS chemicals behave in mixtures is a challenge for evaluating the potential health effects associated with the mixtures people are actually exposed to.
In 2017, the International Agency for Research on Cancer (IARC) classified PFOA as possibly carcinogenic to humans (Group 2B) due to limited evidence in humans, including the associations observed with cancers of the kidney and testis, and animal studies. 61 A similar evaluation for PFOS has not been completed by IARC. 20

PFAS Guidelines, Regulations and Exposure Reduction Measures
While the following guidelines and regulations may not be directly applicable to all Ontario settings, they provide context for interpreting environmental measurements and may help indicate when further investigation of potential PFAS contamination could be useful. Many jurisdictions have derived PFAS guidelines for drinking water, while some guidelines for soil and groundwater are also available. Although PFAS are not specifically regulated in food and consumer products, the Prohibition of Certain Toxic Substances Regulations, 2012 has prohibited the manufacture, use, sale and import of PFAS and PFAS-containing products (with some exceptions). 14 In general, environmental guidelines are developed to be protective of populations and are based on an assumption of lifetime of exposure to a substance (i.e., protective of chronic exposures). During the guideline development process, it is common to factor in a margin of safety or uncertainty factors such that they are protective of sensitive populations and life stages that may be more susceptible to chemical exposures (e.g., those with chronic conditions or young children). 12,31,32 Derivation of guidelines may also take into account other potential sources of exposure to PFAS (e.g., consideration of total exposures from food, water, air, consumer products). 12 Therefore, short-term exposures to PFAS at concentrations above guideline levels are typically not expected to result in health effects. The potential for health risks resulting from prolonged exposures to high levels of PFAS depend on how much and how long a person was exposed.
Different jurisdictions may also take different approaches in deriving guidelines for chemicals in the environment. These approaches may consider, to varying degrees, different factors such as benchmark studies, weight of evidence, technical feasibility, background concentrations, and for certain similar chemicals whether to address them individually or as a group. 18,62

DRINKING WATER
Drinking water guidelines relevant for Ontario and Canada are included in Table B in the Appendix.

Ontario Ministry of the Environment, Conservation and Park's (MECP) interim drinking water guideline
In 2017, following the identification of a 'widespread PFAS release' from firefighting foam that impacted groundwater, the MECP recommended that private drinking water well owners consider treatment if the sum of 11 different PFAS was above 70 ng/L. 63,64

Health Canada Drinking Water Guidelines
Health Canada has developed maximum acceptable concentration (MAC) guideline values for two PFAS; PFOA (200 ng/L) and PFOS (600 ng/L) which are both based on liver effects observed in laboratory studies involving rats. 31,32 The sum of the ratios of the concentrations of PFOS and PFOA relative to their MACs should not exceed 1 to account for the similar mechanism for toxicological effects of PFOA and PFOS. Drinking water screening values for a number of other PFAS are also available from Health Canada. 39 MACs and screening values are designed to protect the health of the general public (including children) from lifetime exposures to the substance (i.e., chronic exposures) in drinking water. 39 As substancespecific information is lacking for most PFAS, future development of guideline values may factor in a grouping approach to consider PFAS as a class of chemicals rather than conducting separate evaluations of individual substances.
In April 2021, Health Canada announced their intention to revisit drinking water guidelines for PFAS. 17 Following this announcement, Health Canada released a proposed objective value for total PFAS for public consultation in February 2023. 65 The proposed objective value is 30 ng/L for the sum of total PFAS in drinking water, with total PFAS defined as the full list of substances analyzed under either US EPA Method 533 (25 PFAS) or US EPA Method 537.1 (18 PFAS), or both. 66,67 As an alternative to using US EPA methodology, jurisdictions can also validate and apply an alternate analytical method for total PFAS with a minimum of 18 PFAS included in the validated method.
The proposed objective value takes into consideration the technical feasibility of drinking water treatment using current technologies, the limit of quantification using recognized analytical methods, and environmental concentrations of PFAS reported by Canadian monitoring data. 65 The proposed objective value is not health-based but Health Canada considers available PFAS toxicity data as generally supportive of the proposed objective. The proposed objective value is intended to serve as an interim guideline while a revision of Health Canada's drinking water guidelines for PFAS is underway. This revision is expected to include a comprehensive review of toxicological data and PFAS risk assessments, a review of new analytical and treatment methods for PFAS, and information on how to manage treatment residuals. 65

United States Environmental Protection Agency Water Health Advisories
The US EPA recently updated their interim drinking water health advisories for PFOA (0.004 ng/L) and PFOS (0.02 ng/L), and also released final drinking water health advisories for PFBS (2000 ng/L) and hexafluoropropylene oxide (HFPO) dimer acid and its ammonium salt (known as "GenX" chemicals, 10 ng/L). 68,69 The drinking water health advisories for PFOA and PFOS are based on a developmental immune health outcome (suppression of tetanus and diphtheria vaccine response, respectively) observed in epidemiological studies. 7 The drinking water health advisories for PFBS and HFPO are based on laboratory studies where thyroid effects were observed in newborn mice following gestational exposures in mothers, and liver effects (lesions) were observed in mice, respectively. 7 The US EPA's health advisories are developed to protect people at all life stages from lifetime (chronic) exposures while accounting for potential exposure sources other than drinking water (e.g., from food, air, consumer products). US EPA's health advisories are not legally enforceable federal standards, but primarily serve to inform drinking water system operators. 70 It is anticipated that the US EPA will be publishing a set of enforceable National Primary Drinking Water Regulations (NPDWRs) for PFAS by the end of 2023. The proposal includes both a non-enforceable Maximum Contaminant Level Goal (MCLG, or the maximum level of a contaminant at which no known or anticipated adverse health effect would occur) and an enforceable standard, or Maximum Contaminant Level (MCL) or Treatment Technique for PFOA and PFOS. While the MCL is set as close as feasible to the MCLG, considerations for the ability to measure and treat a contaminant and related costs/benefits are incorporated into setting the enforceable standard. The MCLG proposed by US EPA is zero nanograms per litre (0 ng/L) for both PFOA and PFOS while the proposed MCL is 4.0 ng/L for both. [71][72][73] In addition, PFNA, PFHxS, PFBS and HFPO dimer acid are addressed as a group. 74 Under the proposed regulation, the measured concentrations of these chemicals will be compared against healthbased concentrations for each chemical and the sum of the four ratios must not exceed 1.0. 74 A select number of individual US states have also enacted their own drinking water regulations for PFAS. Currently, a total of 20 states have established drinking water guidelines for PFOS and/or PFOA with some also having guidelines for other PFAS chemicals. 75

Exposure Reduction Measures for Drinking Water
PFAS are not regularly monitored in drinking water in Canada, but levels are generally expected to be low. 31,32 If a drinking water source is known to be contaminated with PFAS, drinking water system owners can reduce overall exposure by using water treatment, or an alternative water source for drinking, cooking and preparing infant formula. Options can be explored with professionals specialized in water treatment, but examples of treatment processes effective at removing PFAS include adsorption by granular activated carbon (GAC), ion exchange (IX) resin, or high pressure membranes (i.e., nanofilters (NF) and reverse osmosis (RO)). 20,29,76 These can be adapted to suit all sizes of treatment systems. NSF International lists specific water treatment products that have been independently verified to reduce PFOS and PFOA to below 70 ng/L. 77 These will be listed as certified to NSF 53, and/or NSF 58 to specifically include PFOS and PFOA reduction. 77 It is important to follow the manufacturer's recommendations for operation and maintenance of a treatment system (e.g., replacement of filter media).

SOIL
Canadian soil quality guidelines for PFOS are available from the Canadian Council of Ministers of the Environment (CCME). The PFOS soil quality guideline for protection of human health is 0.01 mg/kg for all land uses (agricultural, residential/parkland, commercial and industrial). 78 Although CCME did not develop soil guidelines for PFOA, they note that the health effects associated with PFOS and PFOA are similar and additive effects need to be taken into consideration. Similar to the approach taken by Health Canada, the sum of the ratios of the concentrations of PFOS and PFOA relative to the PFOS soil quality guideline should not exceed 1 to account for additive toxicological effects. 78 Given that the CCME soil guidelines were derived using Health Canada's assessment of health effects, these guidelines may be affected following Health Canada's review of PFAS drinking water guidelines.

GROUNDWATER
The CCME has also developed groundwater quality guidelines for PFOS. CCME groundwater quality guidelines are intended to represent concentrations of contaminants in groundwater below which no appreciable human health risk are expected from long-term (chronic) exposure. 79 The PFOS groundwater guideline for the protection of human health is 0.0006 mg/L (equivalent to 0.6 ng/L) and the sum of the ratios of the concentrations of PFOS and PFOA relative to the PFOS groundwater quality guideline should not exceed 1 to account for the additive toxicological effects of PFOA and PFOS. 78 Given that the CCME groundwater guidelines were derived using Health Canada's assessment of health effects, these guidelines may be affected following Health Canada's review of PFAS drinking water guidelines.

Discussion and Conclusions
The unique physical properties of PFAS have resulted in their widespread use in many consumer products and industrial processes such as paper and cardboard coatings, stain-resistant carpet, non-stick coatings on cookware, and aqueous film-forming foam (AFFF) for fire-fighting. However, the same physical properties have also allowed PFAS to persist in the environment raising public and scientific attention in recent years.
Studies have identified landfills, industrial sites and areas where firefighting activities have occurred as sources of PFAS in the environment. Once in the environment, PFAS can enter groundwater and surface water, and may eventually enter the food chain providing multiple sources of potential exposure for the general public. The sources of exposure may include diet, soil, indoor dust and drinking water, in addition to consumer goods and textiles.
Guidelines for PFAS are most commonly available for drinking water though there are some for soil and groundwater. These guidelines are typically developed to protect populations from chronic exposures to PFAS and incorporate margins of safety. Some drinking water regulatory guidelines have recently been lowered as evidence is emerging on potential health effects.
Animal studies on PFAS exposure show an association with increased liver, reproductive, endocrine, kidney and immunological effects. This is supported by an association with elevated liver enzymes particularly for PFOS and PFOA in cross-sectional epidemiological studies, but human data are otherwise limited and further studies are needed on their clinical significance.
Currently, all Canadians are exposed to some PFAS however health effects cannot be clearly attributed.
Where individuals are exposed to elevated levels of PFAS over an extended period, actions to reduce exposures can be taken. For example, elevated concentrations above applicable guidelines may result from living in areas of known PFAS contamination, or from occupational exposures in a workplace (e.g., individuals working with AFFF). In these situations, efforts to reduce PFAS exposures are generally recommended by various organizations. Measures such as drinking water treatment systems for homeowners with impacted drinking water wells, making informed consumer choices such as purchasing PFAS free products as indicated and following fish consumption guidance in Ontario can reduce overall exposures until more evidence on the health effects of PFAS are established. [80][81][82][83][84]   Maximum concentration of 0.010 µg/g dry-weight from Lake Ontario