As described in the companion Currents in One Health by Brake et al, JAVMA, July 2023, the discovery of per- and polyfluoroalkyl substances (PFAS) was by accident. Roy Plunkett1 was working to develop safer chemical refrigerants when he discovered polytetrafluoroethylene (PTFE) lining a metal cylinder he and his assistant were using. PTFE appeared as a waxy white powder and was initially thought to be a useless inert polymer. The unique structure of the polymer, a carbon-fluorine chain, was stable at high temperatures, resistant to degradation, and able to repel oil and water.
PTFE was the first of many in the family of PFAS. PFAS are organic fluorinated polymers, which means that they are a material made up of large numbers of carbon-fluorine subunits chained together (Figure 1) typically with a polar “head.” The individual species of PFAS are differentiated from one another by the number of carbons in their chain and the type of head group. Historically PFAS polymers were formed through an electrochemical fluorination process2 where the alkyl chains are joined together and cross-linked in the presence of electricity. As time and technology progressed, additional methods have been developed for manufacturing PFAS. The Environmental Protection Agency’s (EPA’s) CompTox Chemicals Dashboard3 currently reports over 14,000 types of PFAS in their database.
PFOA and PFOS are 2 well-known species of PFAS that were used in the manufacture of nonstick pans and stain repellents, respectively. PFOA is a perfluorocarboxylic acid (PFCA) and PFOS is a type of perfluorosulfonic acid (PFSA). The molecules that make up the polar “head” of the PFAS structure lead to its classification. Note the sulfur molecule on PFOS.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
PFOA and PFOS are 2 well-known species of PFAS that were used in the manufacture of nonstick pans and stain repellents, respectively. PFOA is a perfluorocarboxylic acid (PFCA) and PFOS is a type of perfluorosulfonic acid (PFSA). The molecules that make up the polar “head” of the PFAS structure lead to its classification. Note the sulfur molecule on PFOS.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
PFOA and PFOS are 2 well-known species of PFAS that were used in the manufacture of nonstick pans and stain repellents, respectively. PFOA is a perfluorocarboxylic acid (PFCA) and PFOS is a type of perfluorosulfonic acid (PFSA). The molecules that make up the polar “head” of the PFAS structure lead to its classification. Note the sulfur molecule on PFOS.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
PFAS was first used by the US military to protect metal from radioisotopes in the atomic bomb.4 Following World War II, the chemical’s use greatly expanded. Manufacturers began using the chemical and its derivatives to coat wires, reduce friction on gears, seals, and gaskets, protect fabrics, and as a component of ski bindings. One of the most notable uses of PFAS is as the principal component of nonstick surfaces for cookware. Perfluorooctanoic acid (PFOA) was introduced to help smooth out the coatings. Another common use of PFAS is as a surfactant in aqueous fire-fighting foams (AFFF). From the point of its development until 2001, perfluorooctane sulphonate (PFOS) was a major component of AFFF.5,6 PFOS served as a surfactant, allowing the foams to spread and effectively cover and put out fires. PFOS-containing foams have been, and in some places continue to be, used in military bases and airports for training exercises. Frequent use of AFFF on these facilities is responsible for some of the highest levels of PFAS contamination found in drinking water systems today7 and is the recent focus of Agency for Toxic Substances and Disease Registry (ATSDR) human exposure studies.7,8
Prevedouros et al2 estimated that the amount of long-chain perfluoroalkyl carboxylic acids (PFCA) produced and emitted into the environment between 1951 and 2004 is between 3,200 and 6,900 tons with a smaller amount being residual impurities or degradation products.2 However, the 2 most commonly produced PFAS chemicals were PFOA and PFOS (Figure 2).
Tetrafluoroethylene has 2 carbon atoms and 4 fluorine atoms. It binds together in chains and cross-links in a process called polymerization. The result is polytetrafluoroethylene (PTFE). a—Chemical structure of tetrafluoroethylene and its polymerized form, PTFE. b—Simplified schematic of PTFE cross-linked together.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
Tetrafluoroethylene has 2 carbon atoms and 4 fluorine atoms. It binds together in chains and cross-links in a process called polymerization. The result is polytetrafluoroethylene (PTFE). a—Chemical structure of tetrafluoroethylene and its polymerized form, PTFE. b—Simplified schematic of PTFE cross-linked together.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
Tetrafluoroethylene has 2 carbon atoms and 4 fluorine atoms. It binds together in chains and cross-links in a process called polymerization. The result is polytetrafluoroethylene (PTFE). a—Chemical structure of tetrafluoroethylene and its polymerized form, PTFE. b—Simplified schematic of PTFE cross-linked together.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
PFOA, PFOS, and a handful of others are referred to as “legacy PFAS.” Legacy PFAS have long carbon chains (≥ 8 carbons for perfluoroalkyl carboxylate acids such as PFOA and ≥ 6 carbons for perfluoroalkyl sulfonic acids such as PFOS). In the early 2000s, because of the risks to human and animal health, major chemical companies in the United States made a commitment to change the structure of PFAS,9 shortening the chain while still maintaining its desired properties. As a result, worldwide production of the long-chain legacy PFAS, PFOA, and PFOS decreased significantly. Epidemiological studies have shown a corresponding steady decline of the legacy PFAS in human and animal samples and an increase in the newer short-chain PFAS. Short-chain PFAS do not bioaccumulate as much as their long-chain counterparts but persist in the environment and still pose a risk to human and animal health.
Importance of a One-Health Approach to PFAS
The desirable properties of PFAS have led to increased use in manufacturing over the last century.6 Although the introduction and use of these chemicals have improved many aspects of our lives, exposure to this family of chemicals is considered a significant public health threat.
As mentioned in the companion Currents in One Health by Brake et al, JAVMA, July 2023, PFAS are ubiquitous in low levels within soil and water around the world.10 Dust and water can be carried long distances from PFAS contamination sites, making it difficult to pinpoint specific exposure sources for wildlife and other animal groups. Consequently, both long- and short-chain PFAS are present in blood, tissue, and environmental samples11 in areas where there is no known source of contamination. PFAS bioaccumulates in plants and animals and has been linked to altered liver and thyroid function, decreased immune response, and some cancers in humans following exposure. Mounting evidence demonstrates that the adverse health outcomes seen in humans also apply to the animal population.
People and their pets often share drinking water sources, air, and sometimes food—leading to similar sources and levels of exposure.12 The US Geological Survey13 has found PFAS in surface and groundwater in numerous sites across the United States. Contaminated water not only affects drinking water supplies but also affects aquatic fish and plants, which ultimately may be eaten by humans or animals. Elevated PFAS levels in indoor dust and air play a role in PFAS exposures among pets and people.14,15 Additionally, certain textiles produced for pets and children (eg, beds, toys) likely contain PFAS due to the wide usage of PFAS-containing-stain resistant treatments in fabrics and plastics.6,16 The emerging reports of PFAS in marine life, the rapid absorption into plants,17 and the ability to bioaccumulate mean that indirect exposure to PFAS through diet is also an emerging threat.
Due to indoor dogs and cats being exposed to the same environment as their owners, an argument could be made for their use as a sentinel species for PFAS contamination. However, there are gaps in the body of literature regarding primary routes of exposure, the biomarkers of exposure and biomarkers of biological effect, lowest observed adverse effect levels, and half-lives following PFAS exposure in companion animals. Understanding these parameters may alert veterinary clinicians to potential sources of contamination in the home and ultimately protect human and animal lives.
Evaluation of Exposure
What are the primary sources of PFAS for dogs and cats?
Sources of PFAS exposure can be direct, or indirect, meaning that pets and people can be exposed to PFAS precursors or their degradation products. Within a typical household, PFAS exposure most likely occurs through a combination of contaminated water, food, and dust for both humans and animals.18 Children, especially toddlers, are thought to be exposed primarily through mouthing behaviors, such as crawling on carpets and furniture and then putting their hands or toys into their mouths.19 The proximity of small children and household pets to PFAS-treated carpets and floors where dust accumulates, in addition to their mouthing behaviors, potentially places children and pets at similar exposure risk.15,20
Dust—In studying samples from > 2,500 sites around the world, Brusseau et al10 found that background levels of PFAS in soils ranged from 0.001 to 237 µg/kg in areas with no known contamination, whereas PFAS levels in soils from contaminated sites ranged from 0.4 to 460,000 µg/kg. Proximity to industrialized and urban areas factor into animal exposure to long-chain PFAS.11,14 In a study of outdoor air within Korea, Kim et al21 found up to 500 times higher concentrations of volatile PFAS (fluorotelomer alcohols) compounds in urban and industrialized sites compared to their background site. A corresponding study22 investigating PFAS burdens in Oriental Magpies in Korea found that birds living in more urbanized areas had significantly higher PFAS in their livers compared to birds from suburban and rural locations.
Studies in Europe and North America have demonstrated that indoor air and dust have been a greater source of PFAS contamination than outdoor air. The companion Currents in One Health by Brake et al, JAVMA, July 2023, addresses the magnitude of differences between PFAS concentrations in indoor and outdoor air. Although PFAS can be detected outside, Shoeib et al23 demonstrated PFAS concentrations inside could be 100 times greater. Similar findings were reported following a 2013 study of dust in homes across the United States, Canada, and the Czech Republic.
When considering dust exposure in pets or children, it may be better to measure whole house dust rather than vacuum individual pet beds or pieces of furniture. It would be challenging to correlate individual sample results with the many brands of furniture, carpets, or pet beds that are commercially available, much less the infinite combinations of fabric and flooring types. Trudel et al19 have developed an estimated daily intake (EDI) formula for children, which may be appropriate for application to pets.
Water—Drinking water and food are considered the primary routes of exposure in adults, particularly when living in an area with known water contamination. Analyzing data from EPA’s third Unregulated Contaminant Monitoring Rule (UCMR)7 conducted between 2013 and 2015, Hu et al5 estimated that the drinking water of approximately 6 million people serviced by public water systems within the United States was contaminated with PFAS above EPA’s 2016 health advisory recommendations of 70 ppt.24 PFAS levels were highest in public water systems located near military sites and airports that used AFFF in fire-fighting training exercises, manufacturing facilities that produced or used PFAS, and wastewater treatment plants.5
Although most of the water systems denoted as having high PFAS concentrations during the third UCMR have been remediated, serum PFAS levels in the people living in those areas are still elevated. In 2022, ATSDR published the results7,8 of an exposure assessment conducted in 10 sites with high levels of contamination as reported by the third UCMR. The 10 sites chosen were located near current or former US military bases with known use of AFFF in military training exercises. ATSDR reported maximum PFAS in drinking water as high as 3,100 ppt of PFOS in Moose Creek, AK; 2,900 ppt of PFOA in Lubbock County, TX; and 1,500 ppt of perfluorohexanoic acid (PFHxA) in Airway Heights, WA,8 which correlated with serum PFAS levels of residents.
We know PFAS in drinking water is a risk for animals. PFAS runoff from facilities using AFFF in Australia had contaminated the drinking water of nearby farms and resulted in increased serum PFAS levels of the livestock raised there.11,25 Within the United States, at least 1 dairy farm has been depopulated due to exposure to PFAS-contaminated water26 directly linked to a nearby military base. It is important to look at the drinking water sources, as well as PFAS use in nearby facilities when considering drinking water exposure.
Diet—Untangling the potential exposures through diet is particularly challenging because of the variety of foods and sources of foods that are eaten by pets. In his assessment of the amount of PFAS produced and its disposition, Prevedouros et al2 suggested that perfluorooctanoate accumulated in sediments and in the oceans, where currents transport PFAS around the world. Aquatic plants and animals near the bottom of the food chain absorb the substances and serve as sources of PFAS for higher trophic levels. Consequently, concentrations of PFAS have been found in both marine mammals and fish.27,28 As addressed in the companion Currents in One Health by Brake et al, JAVMA, July 2023, PFAS was found in nearly 99% of commercial fishmeal with total concentrations ranging from 0.65 to 85.5 μg/kg.29 Fish and fish byproducts, such as fishmeal, are frequently used in animal feeds, which could put both our large and small veterinary patients at risk.30,31
Run-off from contaminated ground, rain, and the injection of biosolids into the ground as fertilizer are all sources of PFAS for terrestrial flora.17 The uptake of PFAS in plants differs by chain length and plant species, but there is a direct correlation between the amount of contamination and plant uptake.3 In reviewing studies related to PFAS exposure from agricultural plants, Ghisi17 and Felizeter32 surmised that small-chain PFAS accumulate in leaves and fruits, whereas the longer chain PFAS seemed to concentrate in the roots. Blaine et al33 found this to be true when comparing PFAS distribution to various pant compartments of edible crops exposed to PFAS. The highest concentrations of long-chain PFAS were found in radish roots, celery shoots, and in pea fruit, respectively. Stahl et al34 found that absorption of PFAS into plants decreased significantly with chain length and that PFAS tended to accumulate more in the stalks or “straw” of wheat, rye, barley, and canola rather than the kernels. Absorption of PFAS into plants is particularly important since these crops are critical components of silage fed to livestock and can make up a significant portion of commercial pet food ingredients.
The idea that animal feeds could be a contributor to PFAS exposure in cattle was demonstrated by Vestergren et al.35 In his study of a Swedish dairy farm with no known sources of PFAS contamination, the researchers found that of all the food and water the cattle consumed, silage made from crops grown on the farm was the primary route of PFAS exposure. In 2016, a dairy farm in Maine, US, was depopulated due to PFAS-contaminated feed. Although the producer had installed a water treatment system and purchased new cows after discovering PFAS contamination on his farm, PFAS turned up again in the milk and manure of his animals. The recurring presence of PFAS was attributed to feeding hay grown on soil contaminated by years of fertilizing with sewage sludge (biosolids).26 PFAS contamination of soil and crops is also responsible for shuttering a cattle company in Michigan. In January 2022, the Michigan Department of Agriculture and Rural Development issued a consumption advisory following discovery of PFOS in beef samples. The farm in question used biosolids from a waste treatment plant as fertilizer for their fields.36
Fish, grains, meat, and dairy products are all important components of human and animal diets and may be a significant source of PFAS exposure.28,35,37,38 Dietary studies16,38 conducted within Europe, Canada, and the United States have determined that the amount of PFAS consumed through food was less than EPA’s reference dose for adults. In contrast, studies among Inuit people living in Nunavik, the northernmost region of Quebec, Canada, found long-chain PFAS levels at 4 to 7 times greater than the Canadian population.39 This corresponds directly to the PFAS levels found in “natural foods” of the population, marine mammals, and seafood.
Just as with human diets,24,38 the risks of PFAS exposure among pets consuming commercial pet foods are not well understood. An exploratory study40 conducted by Chinthakindi et al using 11 different brands of popular dog and cat food sold within the United States demonstrated that nearly 30% of the samples contained PFCAs with total PFCA concentrations ranging from less than the limit of detection to 3.67 ng/g. Four of the 9 PFCAs were measurable: perfluorobutanoic acid (PFBA), PFHxA, perfluoroheptanoic acid (PFHpA), and PFOA. Of these, PFBA was found in the highest concentrations.
Chinthakindi et al40 then conducted oxidation studies on the pet foods to determine whether the presence of fluorotelomer alcohols (which are PFAS pre-cursers and used in pet food packaging) could degrade into the PFCAs of interest. After subjecting the samples to the total oxidizable precursor assay, the laboratory found detectable levels for 8 of the 9 PFCAs analyzed.
Chinthakindi et al40 used data before and after oxidation to calculate the EDI of PFAS that can be attributed to pet foods. Before oxidation, the EDI was 14.2 ng/kg body weight/day for cats and 14.1 ng/kg body weight/day for dogs.40 This value is lower than the EPA’s reference dose in humans (20 ng/kg body weight/day).24 However, when inputting the oxidized sample into the equation, the EDI of cats and dogs is 95.2 ng/kg body weight/day and 125 ng/kg body weight/day, respectively, which exceeds the human reference dose. There is no reference dose for PFAS in dogs and cats. Chinthakindi et al40 concluded that pet food itself may not be a significant risk in pets but that pet food packaging, which includes precursors to several PFCAs, may be a larger problem.
As addressed in the companion Currents in One Health by Brake et al, JAVMA, July 2023, PFAS has been authorized by FDA for use in food contact surfaces since the 1960s. It is a well-known coating for the inside of microwave popcorn bags, pizza boxes, and fast-food wrappers. Small amounts of PFAS do leak from coated food-contact surfaces into human-grade food, particularly into oils or emulsified foods like butter,41 and it is likely that coatings on pet food packaging do the same.
Maternal transfer—Evidence of maternal transfer of PFAS to the fetus and through lactation has been documented in humans and animals. Kim et al42 collected maternal blood, umbilical cord serum, and breast milk from 20 volunteers in Seoul, Korea in 2007. Six PFCAs were detected in all maternal and cord serum samples, while 3 were found in breast milk. Of all the PFCAs, PFOS was found in highest concentration across the 3 tissues sampled—making up 94% of the total PFCA concentration in breast milk. Kim et al concluded that the transfer of PFCAs between maternal serum and umbilical cord depended on the length of the carbon chain and the type of PFAS. Regardless of which type of PFAS was found, breast milk concentrations were several orders of magnitude less than maternal serum. Hinderliter et al43 discovered a similar phenomenon when conducting pharmacokinetic studies of PFOA on pregnant rats. After dividing the rats into subgroups, Hinderliter et al administered a daily dose of 3, 10, or 30 mg/kg/day starting on gestation day 4. PFOA was found in the amniotic fluid, placentas, fetuses, and milk of the rats at rates proportional to the dose. The concentration of PFAS in milk was steady state throughout the lactation period and represented about 10% of the concentration found in maternal plasma. Maternal transfer of PFAS has been documented in multiple other species including birds, fish, cattle,30,37 and marine mammals.11,30,44,45 Based on these observations, maternal transfer likely occurs in pets as well and could be an area of future study.
Dermal exposure—Dermal exposure in pets has not been well described. Besides contact with floors and furniture treated with PFAS-containing products, dogs and cats may also be at risk from popular flea and tick prevention. The environmental watchdog, Public Employees for Environmental Responsibility (PEER), commissioned laboratory analysis of a flea and tick collar and a topical flea and tick preventative.46 Four types of PFAS, PFHxA, PFHpA, perfluoroheptane sulfonate (PFHpS), and hexafluoropropylene oxide dimer acid (GenX), were measured in the topical product for a total of 2,390 ng/L. The collar contained 0.25 ng/g perfluorododecane sulfonate.47
In addition to the flea and tick products mentioned, researchers have found that when increasing concentrations of PFOA are applied to the skin of mice, there was a corresponding increase in serum PFOA levels.48 Whitehead et al49 evaluated 231 human cosmetic products purchased in the United States and Canada and found that foundations, mascaras, and lip products had the highest proportion of total fluorine. PFAS concentrations ranged from 22 to 10,500 ng/g product weight with the highest amounts of PFAS found in foundation and lip products. Investigators are still working out the risks of using PFAS-containing cosmetics. In the same way, more work should be done to investigate the risk of topical flea and tick preventatives in animals.
Are serum PFAS levels in dogs and cats comparable to humans?
In at least 2 studies, researchers have found that serum PFAS levels in cats were similar to levels found in humans. Bost et al20 collected serum from cats in clinics and shelters in Raleigh, NC, and analyzed samples for 9 different PFAS. The team found at least 1 species of measured PFAS in all but 1 of their samples (98.6%). The most frequently found analytes were PFOS (in 97% of the samples), perfluorononanoic acid (PFNA; 93%), and PFOA (82%) with the largest concentrations being PFOS and PFHxS, respectively. The research team found similar PFAS profiles between cats and humans when they compared their findings with those reported by human data in the 2007–2009 National Health and Nutrition Examination Survey (NHANES).
In a separate study, Wang et al50 sampled cats within the San Francisco Bay region of California during 2 different time periods, 2008–2010 and 2012–2013, and compared serum PFAS levels to that of human sera collected in 2009 from the same region. Of the 12 PFAS which were analyzed during the time periods, Wang et al50 found that cats and people had similar PFAS profiles, with PFAS and PFOA being the dominant species. When feline serum PFAS levels across the 5-year time span were compared with human data from NHANES during the same time periods, researchers again noted that PFAS profiles were similar between cats and humans and that PFOA and PFOS in both data sets declined similarly over time. These cross-sectional studies demonstrate that at any given time, PFAS levels among cats are similar to their human counterparts. Although extremely important, we do not know the half-life of PFAS in cats nor do these studies take into consideration the magnitude or route of exposure. More information is needed to determine whether or not cats could be good sentinel species for human exposure.
To date, there has not been a study comparing serum PFAS levels between dogs and humans. However, work has been done examining the amount and types of PFAS in dog sera. A study51 conducted with laboratory beagles and police dogs in China found a number of PFAS species in all of the sera tested. The average concentration of PFAS was 3.553 ng/ml with PFOA the most common PFAS found, followed by PFBA and PFOS. Since the half-lives of PFAS are so short in dogs compared to humans, comparing serum PFAS levels following a single exposure or an exposure that has been mitigated may not be appropriate if a long time has elapsed. Overall, pets could be accurate sentinels for human health, particularly for sustained exposures in the home due to contaminated dust or drinking water.
Can dog and cat exposure to PFAS be diagnosed from blood chemistry or clinical signs?
Human epidemiological and laboratory animal studies have demonstrated that PFAS exposure can impact the health of individuals. The C8 study,52 conducted among people working in and around a Teflon manufacturing facility in West Virginia, found probable associations between exposure to high levels of PFOA and kidney cancer, testicular cancer, pregnancy-induced hypertension, thyroid disease, high cholesterol, and ulcerative colitis. Though the geometric mean of serum PFOA concentrations found in the C8 was an order of magnitude higher than documented in the dog and cat studies cited here. There is mounting evidence that animals experience similar adverse events following exposure to PFAS. PFAS exposure in companion animals may impact body condition scores, blood chemistry levels, fetal development, as well as multiple body systems (hepatic, respiratory, immunological, amongst others).18,50,51,53,54 To date, PFAS has been significantly linked to changes in kidney and liver function in both dogs51 and cats20,54 and has been positivily associated with obesity,20 pleural effusion,20 and altered thyroid function20,50,54 in cats (Figure 3).
Major organs affected by PFAS can differ depending on species and sex. To date, PFAS has been linked to developmental delays, liver damage, immune suppression, some cancers, and disruption of the endocrine system in humans. Limited research indicates that cats may be subject to respiratory effusion, liver damage, and hyperthyroidism. PFAS appears to impact liver and kidney function in dogs.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
Major organs affected by PFAS can differ depending on species and sex. To date, PFAS has been linked to developmental delays, liver damage, immune suppression, some cancers, and disruption of the endocrine system in humans. Limited research indicates that cats may be subject to respiratory effusion, liver damage, and hyperthyroidism. PFAS appears to impact liver and kidney function in dogs.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
Major organs affected by PFAS can differ depending on species and sex. To date, PFAS has been linked to developmental delays, liver damage, immune suppression, some cancers, and disruption of the endocrine system in humans. Limited research indicates that cats may be subject to respiratory effusion, liver damage, and hyperthyroidism. PFAS appears to impact liver and kidney function in dogs.
Citation: American Journal of Veterinary Research 84, 7; 10.2460/ajvr.22.12.0221
Liver enzymes and cholesterol—In human and laboratory animal studies, PFAS exposure is associated with liver changes. As covered in the companion Currents in One Health by Brake et al, JAVMA, July 2023, article, PFAS activates the peroxisome proliferator-activated receptor-α in hepatocytes, which ultimately leads to liver enlargement due to accumulation of cholesterol in the liver and hypertrophy of hepatocytes. In reviewing data from the general population gathered by the NHANES studies in 1999–2000, 2003–2004, and 2007–2010, researchers found consistent associations between serum PFAS levels and increased liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT], and gamma-glutamyl transferase [GGT]).55,56 Laboratory rodent and nonhuman primate studies also demonstrated links between exposure to certain types of PFAS and increases in liver weight,57,58 altered serum lipid levels, and elevated liver enzymes.42,57,59
Outside of the laboratory the findings are different. You et al51 explored PFAS’s influence on liver enzymes in police dogs and laboratory beagles by analyzing individual blood chemistry components with several different types of PFAS. The results indicated that different species of PFAS could significantly alter blood chemistry parameters in different ways. For example, PFNA and perfluorodecanoic acid (PFDA) were both significantly associated with an increase in cholesterol while PFOA and PFOS were significantly associated with a decrease in cholesterol.51 Only 2 of the species measured, 6:2 chlorinated polyfluorinated ether sulfonate and PFDA, were associated with significant differences in alkaline phosphatase in their study. In analyzing sera of cats in Swedish households, Weiss et al54 could not find a significant association between cholesterol levels and PFOA or PFOS but did find a significant increase in cholesterol associated with total PFAS levels. In the C8 project participants, there were also discrepancies in the biochemistry results. Some researchers18 found associations between serum PFOA levels and ALT and bilirubin while others did not.
Thyroid hormones—In their 2021 PFAS Toxicological Profile,18 ATSDR concluded that there is a relationship between PFAS exposure and altered thyroid function but cautions that results are not consistent across human or animal studies. As with liver enzymes, the findings on PFAS and thyroid hormone seem to differ based on the type of PFAS and the study conducted. As Winquist et al52 found, sometimes a single study reveals different results. In their retrospective cohort study of C8 participants, they found positive associations between PFOA exposures and both hypothyroidism and hyperthyroidism among women participants in the C8 study,60 whereas only hypothyroidism was seen in men.
No data have been reported for thyroid function disruption in dogs, although studies conducted by Wang et al,50 Bost et al,20 and Weiss et al54 have pointed to some disruption in cats. In a study of 72 cats in North Carolina, Bost et al20 discovered that PFAS was detectable in all but 1 of their cat samples with PFOS and PFHxS being the most common compounds measured. Bost reported a significant association between hyperthyroidism and serum PFOA levels and a weaker association between hyperthyroidism and total PFAS.20 These findings correspond with a similar study conducted by Wang et al50 in California. In studying hyperthyroidism in cats living in the San Francisco Bay area, Wang et al50 found that PFOA and PFHxS levels were significantly higher in hyperthyroid cats compared to nonhyperthyroid cats. Swedish researchers found that all of their feline samples tested for PFAS contained PFOA, PFDA, PFOS, and perfluoroundecanoic acid (PFUnDA).54 The team reported a significant positive increase in serum total T4 levels with increasing PFNA levels but did not see a correlation between serum PFAS and thyroxine (T4), TSH thyroid-stimulating hormone (TSH), or the T4/TSH ratio.
The question of how PFAS disrupts thyroid function remains unsolved. After finding that high serum PFOA and PFOS levels were associated with hypothyroidism among participants in the C8 study, Knox et al61 hypothesized that PFAS-induced production of thyroid-binding globulin in the presence of PFAS was to blame. Hamers et al62 tested binding affinities of several compounds found in household dust to an important thyroid hormone carrier protein, transthyretin (TTR). They found that while PFAS does bind to transthyretin, its affinity was not as strong as that of the actual target protein thyroxine. This indicates that while PFAS species may compete for TTR in the signaling pathway they cannot completely competitively inhibit the binding of T4 and thus prevent normal thyroid functions on this pathway. Still, ATSDR and others have found that there is a significant correlation between PFAS exposure, disruption of free T4 and thyroid function. While there is no clear relationship between PFAS binding to TTR compounds and circulating T4, there appears to be some relationship between thyroid function and exposure to PFAS compounds in house dust.
Body mass—The question of whether PFAS exposure contributes to obesity largely remains unanswered. In a systematic review of 19 maternal studies evaluating the association between prenatal persistent organic pollutants exposure and childhood obesity, Stratakis et al63 found no associations between PFAS exposure in utero and childhood obesity. In a retrospective cohort study of nearly 9,000 adults living in the Mid-Ohio Valley region, Barry et al64 also could not find significant correlations between PFAS exposure in early childhood and body mass. Alternatively, in a study of 803 children enrolled in a National Institute of Child Health and Human Development Fetal Growth Study, Bloom et al65 found gestational exposure to PFUnDA in some women was positively associated with childhood adiposity. Similarly, in a study of 940 adolescents, Averina et al18 reported that PFHxS and PFHpS concentrations were positively associated with obesity.
In companion animals, the data on obesity and exposure are scarce. Bost et al20 found a significant relationship between PFAS concentration and body weight among cats in North Carolina, US. Statistical analysis revealed a strong association with body weight in PFOS and PFHxS but not PFOA or C9. Laboratory animal findings are the opposite. The 2021 PFAS Toxicological Profile reports that exposures to PFAS “have consistently shown decreases in body weight or decreases in body weight gain.”18
Respiratory effusion—To date, there have been very few studies evaluating respiratory endpoints in humans exposed to PFAS. Epidemiological studies of humans with known exposure to PFOA have mixed results. Workers at the Washington Works Plant, who presumably would have high levels of exposure, did not seem to be affected. Conversely, residents living near the plant reported a significant increase in chronic bronchitis and shortness of breath.18 Respiratory disease has been documented in both laboratory animals and cats for PFOA, PFOS, and PFHxS. Bost et al20 divided cats into 4 distinct quartiles according to their serum PFAS concentrations in their study. Three of the cats in their study suffered respiratory effusion, and significantly greater PFHxS levels were demonstrated in all 3 cats with respiratory disease. The authors hypothesized that since PFAS is known to embed in lipid bilayers, it may disrupt the surface tension of a particular lung surfactant common in cats, dipalmitoylphosphatidylcholene. A similar finding was reported in laboratory animals. Inhalation exposure of very high concentrations of PFOS and PFOA dust induced wheezing and nasal discharge.18 Prolonged exposure to the sodium salt of PFHxA resulted in a reversible degeneration of the nasal olfactory epithelium in rats.66
Pharmacokinetics of PFAS
Although exposure and absorption of PFAS across species are comparable, there are still some unique differences between humans and companion animals, which may prevent a direct comparison. To address the question of whether PFAS levels in pets can be compared to that of their owners, we first need to learn whether or not proteins that bind and transport PFAS throughout the body are different between animal species and humans; differences may affect how long and where PFAS can circulate.
Distribution—During exposure, PFAS is rapidly absorbed into the bloodstream and binds quickly to transport proteins. High concentrations of both PFOS and PFOA have been found in serum, liver, and kidneys of laboratory animals exposed to the chemicals with smaller amounts found in the skin, spleen, and reproductive orgins (Figure 3).67 Distribution of PFAS is related to the dose: at smaller doses, a larger proportion of PFAS concentrates in the liver compared to larger doses where concentrations are more evenly distributed between organs.68
The protein-binding properties and level of resorption (ie, enterohepatic recirculation) of PFAS in the body increases with the number of carbon atoms. In the same way, transporter proteins and carbon-chain length also influence how PFAS are eliminated from the body.53 PFAS can be eliminated via urine or feces, lactation, pregnancy, and menstruation. However, depending on the specific chemical, sex, and animal species-specific properties, elimination rates differ and influence the half-lives of PFAS.14,18,22,53 For example, the half-life of PFOS in mice ranges from days to weeks, while in pigs it is almost 2 years (634 days).14,69 For PFOA, the half-life could be as short as 2 hours in mice, while in pigs the half-life of the same compound was 236 days.69 In dogs, the half-life of PFOA ranged between 8 and 30 days.70 At the time of this writing, there was no report for half-lives in cats. When analyzing data from retired fluorochemical production workers, Olsen et al71 recorded mean half-lives of PFOS, PFHS, and PFOA as 5.4 years (95% CI, 3.9 to 6.9), 8.5 years (95% CI, 6.4 to 10.6), and 3.8 years (95% CI, 3.1 to 4.4), respectively.
Sex and species differences—In oral and inhalation studies, researchers found a difference in the absorption and excretion of PFAS by species and sex. When a single oral dose of radiolabeled ammonium perfluorooctanate was administered to male and female mice, rats, hamsters, and rabbits, Hundley et al67 found that the male and female rabbits, the female rat, and the male hamsters all excreted more than 99% of the original dosing within 120 hours, while the male rat and the female hamster excreted 39% and 60% of the dose within the same time frame. When exposing rats to aerosolized PFOA, Hinderliter et al72 found the time to maximum plasma concentrations took much longer in male rats than in female rats. A similar trend occurred when the plasma PFOA concentrations returned to baseline. Species and sex differences found in inhalation and gastrointestinal studies may also apply to dermal absorption.
Conclusion
In 2022, the National Academies of Science, Engineering, and Medicine published a report73 suggesting that the ATSDR recommend biomonitoring as part of their clinical guidance for human patients exposed to PFAS. Although some of the recommended screening is routine, the tests chosen and frequency of monitoring are based on the level of serum PFAS concentrations found in the patient.
There are many aspects to consider before making this recommendation. Clinicians will have to identify people who are exposed; determine the length of time biomonitoring should be conducted; decide if additional, sometimes invasive, procedures should be conducted; and find the funds to pay for it all. Another consideration is the challenge of finding facilities and tests that can analyze PFAS. There are several laboratories across the country that are certified to test PFAS. However, testing is expensive and often limited to water samples. In addition, private testing of dust and foods may not be offered, unless it is part of a larger study. Unless a patient was living in an area with documented contamination, they may never know if they have been exposed.
Scientific research suggests that we may soon have the tools to effectively use dogs and cats as predictors of human exposure. Researchers have demonstrated that PFAS can be detected in cats and dogs and that levels of individual types of PFAS positively correlate with those found in human samples.50 Because of the limited half-life of PFAS in dogs, it can be predicted that changes in body systems and the overall health of pets exposed to toxic substances may appear months or even years before their human counterparts. This could mean that like canaries who stood watch over miners in days of old, dogs and cats may be able indicators of harmful exposures in the household.
Despite the efforts of many to try to reduce or prohibit the use and manufacture of certain types of PFAS, the chemical is here to stay. Indoor dogs and cats largely live on the same flooring and furniture, breathe in the same air, and drink the same water as their human counterparts. Using dogs and cats as sentinels for human exposure in the household will be an important component in identifying risks and preserving healthy outcomes for the people who live there.
Acknowledgments
The authors thank Kevin Smith for the graphics and Dr. George Parlavantzas, Karen Scruton, and Dr. Rachel Rogers for their technical expertise.
This work was supported by the Michigan State University, College of Veterinary Medicine, Center for Comparative Epidemiology.
Dr. Heather Brake is the Director of Communications at the CDC, National Center for Environmental Health/Agency for Toxic Substances and Disease Registry. This paper is written as part of her doctoral degree program at Michigan State University, College of Veterinary Medicine. Information in this article does not constitute nor imply endorsement by CDC or the US Department of Health and Human Services.
References
- 2.↑
Prevedouros K, Cousins IT, Buck RC, Korzeniowski SH. Sources, fate and transport of perfluorocarboxylates. Environ Sci Technol. 2006;40(1):32–44. doi:10.1021/es0512475
- 3.↑
US Environmental Protection Agency. Comptox Chemicals Dashboard: Master List of PFAS Substances (Version 2). Accessed November 21, 2022. https://www.michigan.gov/mdard/about/media/pressreleases/2022/01/28/grosticcattle-company-of-livingston-county-beef-sold-directly-to-consumers-may-contain-pfos
- 4.↑
Gorzelnik S. PFAS discovery. Gorzelnik Engineering. Accessed October 14, 2022. https://gorzelnikengineering.com/pfas-discovery/
- 5.↑
Hu XC, Andrews DQ, Lindstrom AB, et al. Detection of poly- and perfluoroalkyl substances (PFASs) in U.S. drinking water linked to industrial sites, military fire training areas, and wastewater treatment plants. Environ Sci Tech Lett. 2016;3(10):344–350. doi:10.1021/acs.estlett.6b00260
- 6.↑
Gluge J, Scheringer M, Cousins IT, et al. An overview of the uses of per- and polyfluoroalkyl substances (PFAS). Environ Sci Proc Impacts. 2020;22(12):2345–2373. doi:10.1039/d0em00291g
- 7.↑
US Environmental Protection Agency. UCMR3 (2013–2015) Occurance Data. US Environmental Protection Agency; 2015.
- 8.↑
Agency for Toxic Substances and Disease Registry. PFAS Exposure Assessments Final Report: Findings across Ten Exposure Assessment Sites. Agency for Toxic Substances and Disease Registry; 2022.
- 9.↑
3M. 3M phasing out some of its specialty materials. 3BL CSRWire. 2000. Accessed September 18, 2022. https://www.csrwire.com/press_releases/25065-3m-phasing-out-some-of-its-specialty-materials
- 10.↑
Brusseau ML, Anderson RH, Guo B. PFAS concentrations in soils: background levels versus contaminated sites. Sci Total Environ. 2020;740:140017. doi:10.1016/j.scitotenv.2020.140017
- 11.↑
Braunig J, Baduel C, Heffernan A, Rotander A, Donaldson E, Mueller JF. Fate and redistribution of perfluoroalkyl acids through AFFF-impacted groundwater. Sci Total Environ. 2017;596:360–368. doi:10.1016/j.scitotenv.2017.04.095
- 12.↑
CDC. Healthy pets healthy people. Centers for Disease Control and Prevention. Accessed January 30, 2023. http://www.cdc.gov/healthypets
- 13.↑
US Geological Survey. Explore search: PFAS. Accessed June 13, 2022. https://www.usgs.gov/search?keywords=PFAS+
- 14.↑
Death C, Bell C, Champness D, Milne C, Reichman S, Hagen T. Per- and polyfluoroalkyl substances (PFAS) in livestock and game species: a review. Review. Sci Total Environ. 2021;774(12):144795. doi:10.1016/j.scitotenv.2020.144795
- 15.↑
Kotthoff M, Muller J, Jurling H, Schlummer M, Fiedler D. Perfluoroalkyl and polyfluoroalkyl substances in consumer products. Environ Sci Pollut Res. 2015;22(19):14546–14559. doi:10.1007/s11356-015-4202-7
- 16.↑
Tittlemier SA, Pepper K, Seymour C, et al. Dietary exposure of Canadians to perfluorinated carboxylates and perfluorooctane sulfonate via consumption of meat, fish, fast foods, and food items prepared in their packaging. J Agric Food Chem. 2007;55(8):3203–3210. doi:10.1021/jf0634045
- 17.↑
Ghisi R, Vamerali T, Manzetti S. Accumulation of perfluorinated alkyl substances (PFAS) in agricultural plants: a review. Environ Res. 2019;169:326–341. doi:10.1016/j.envres.2018.10.023
- 18.↑
Averina M, Brox J, Huber S, Furberg A-S. Exposure to perfluoroalkyl substances (PFAS) and dyslipidemia, hypertension and obesity in adolescents. The Fit Futures study. Environ Res. 2021;195:110740. doi:10.1016/j.envres.2021.110740
- 19.↑
Trudel D, Horowitz L, Wormuth M, Scheringer M, Cousins IT, Hungerbühler K. Estimating consumer exposure to PFOS and PFOA. Risk Analysis. 2008;28(2):251–269. doi:10.1111/j.1539-6924.2008.01017.x
- 20.↑
Bost PC, Strynar MJ, Reiner JL, et al. U.S. domestic cats as sentinels for perfluoroalkyl substances: possible linkages with housing, obesity, and disease. Environ Res. 2016;151:145–153. doi:10.1016/j.envres.2016.07.027
- 21.↑
Kim S-K, Shoeib M, Kim K-S, Park J-E. Indoor and outdoor poly- and perfluoroalkyl substances (PFASs) in Korea determined by passive air sampler. Environ Pollut. 2012;162:144–150. doi:10.1016/j.envpol.2011.10.037
- 22.↑
Park K, Barghi M, Lim JE, et al. Assessment of regional and temporal trends in per- and polyfluoroalkyl substances using the Oriental Magpie (Pica serica) in Korea. Sci Total Environ. 2021;793:148513. doi:10.1016/j.scitotenv.2021.148513
- 23.↑
Shoeib M, Harner T, Ikonomou M, Kannan K. Indoor and outdoor air concentrations and phase partitioning of perfluoroalkyl sulfonamides and polybrominated diphenyl ethers. Environ Sci Tech. 2004;38(5):1313–1320. doi:10.1021/es0305555
- 24.↑
US Environmental Protection Agency. Drinking Water Health Advisory for Perfluorooctane Sulfonate (PFOS). US Environmental Protection Agency; 2016.
- 25.↑
Drew R, Hagen TG, Champness D. Accumulation of PFAS by livestock – determination of transfer factors from water to serum for cattle and sheep in Australia. Food Add Contam Part A. 2021;38(11):1897–1913. doi:10.1080/19440049.2021.1942562
- 26.↑
Schroeder MC, Bolin JS. PFAS: an emerging threat to the environment…and dairy farms. Dairy Business. DairyBusinesss, LLC; 2019.
- 27.↑
Fair PA, Houde M, Fossi MC, Panti C. Chapter 5–Poly- and perfluoroalkyl substances in marine mammals. In: Marine Mammal Ecotoxicology. Academic Press; 2018:117–145.
- 28.↑
Fair PA, Wolf B, White ND, et al. Perfluoroalkyl substances (PFASs) in edible fish species from Charleston Harbor and tributaries, South Carolina, United States: exposure and risk assessment. Environ Res. 2019;171:266–277. doi:10.1016/j.envres.2019.01.021
- 29.↑
Li X, Dong S, Zhang W, et al. The occurrence of perfluoroalkyl acids in an important feed material (fishmeal) and its potential risk through the farm-to-fork pathway to humans. J Hazard Mater. 2019;367:559–567. doi:10.1016/j.jhazmat.2018.12.103
- 30.↑
Guruge KS, Manage PM, Yamanaka N, Miyazaki S, Taniyasu S, Yamashita N. Species-specific concentrations of perfluoroalkyl contaminants in farm and pet animals in Japan. Chemosphere. 2008;73(1):S210–S215. doi:10.1016/j.chemosphere.2006.12.105
- 31.↑
Suominen K, Hallikainen A, Ruokojärvi P, et al. Occurrence of PCDD/F, PCB, PBDE, PFAS, and organotin compounds in fish meal, fish oil and fish feed. Chemosphere. 2011;85(3):300–306. doi:10.1016/j.chemosphere.2011.06.010
- 32.↑
Felizeter S, McLachlan MS, de Voogt P. Uptake of perfluorinated alkyl acids by hydroponically grown lettuce (Lactuca sativa). Environ Sci Tech. 2012;46(21):11735–11743. doi:10.1021/es302398u
- 33.↑
Blaine AC, Rich CD, Sedlacko EM, et al. Perfluoroalkyl acid distribution in various plant compartments of edible crops grown in biosolids-amended soils. Environ Sci Tech. 2014;48(14):7858–7865. doi:10.1021/es500016s
- 34.↑
Stahl T, Heyn J, Thiele H, et al. Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from soil to plants. Arch Environ Contam Toxicol. 2009;57(2):289–298. doi:10.1007/s00244-008-9272-9
- 35.↑
Vestergren R, Orata F, Berger U, Cousins IT. Bioaccumulation of perfluoroalkyl acids in dairy cows in a naturally contaminated environment. Environ Sci Pollut Res. 2013;20(11):7959–7969. doi:10.1007/s11356-013-1722-x
- 36.↑
Michigan Department of Agriculture and Rural Development. Consumption advisory: Grostic Cattle company of Livingston county beef sold directly to consumers may contain PFOS. 2022. Accessed December 15, 2022. https://www.michigan.gov/mdard/about/media/pressreleases/2022/01/28/grostic-cattle-companyof-livingston-county-beef-sold-directly-to-consumers-may-contain-pfos
- 37.↑
Kowalczyk J, Ehlers S, Oberhausen A, et al. Absorption, distribution, and milk secretion of the perfluoroalkyl acids PFBS, PFHxS, PFOS, and PFOA by dairy cows fed naturally contaminated feed. J Agric Food Chem. 2013;61(12):2903–2912. doi:10.1021/jf304680j
- 38.↑
Hlouskova V, Hradkova P, Poustka J, et al. Occurrence of perfluoroalkyl substances (PFASs) in various food items of animal origin collected in four European countries. Food Addit Contam Part A Chem. 2013;30(11):1918–1932. doi:10.1080/19440049.2013.837585
- 39.↑
Aker A, Ayotte P, Caron-Beaudoin E, et al. Plasma concentrations of perfluoroalkyl acids and their determinants in youth and adults from Nunavik, Canada. Chemosphere. 2023;310:136797. doi:10.1016/j.chemosphere.2022.136797
- 40.↑
Chinthakindi S, Zhu H, Kannan K. An exploratory analysis of poly- and per-fluoroalkyl substances in pet food packaging from the United States. Environ Sci Tech. 2021:21:101247. doi:10.1016/j.eti.2020.101247
- 41.↑
Begley TH, Hsu W, Noonan G, Diachenko G. Migration of fluorochemical paper additives from food-contact paper into foods and food simulants. Food Addit Contam Part A Chem. 2008;25(3):384–390. doi:10.1080/02652030701513784
- 42.↑
Kim S-K, Lee KT, Kang CS, et al. Distribution of perfluorochemicals between sera and milk from the same mothers and implications for prenatal and postnatal exposures. Environ Pollut. 2011;159(1):169–174. doi:10.1016/j.envpol.2010.09.008
- 43.↑
Hinderliter PM, Mylchreest E, Gannon SA, Butenhoff JL, Kennedy GL. Perfluorooctanoate: placental and lactational transport pharmacokinetics in rats. Toxicology. 2005;211(1):139–148. doi:10.1016/j.tox.2005.03.010
- 44.↑
Wu Y, Simon KL, Best DA, Bowerman W, Venier M. Novel and legacy per- and polyfluoroalkyl substances in bald eagle eggs from the Great Lakes region. Environ Pollut. 2020;260:10. 113811. doi:10.1016/j.envpol.2019.113811
- 45.↑
Taylor S, Terkildsen M, Stevenson G, et al. Per and polyfluoroalkyl substances (PFAS) at high concentrations in neonatal Australian pinnipeds. Sci Total Environ. 2021;786:147446. doi:10.1016/j.scitotenv.2021.147446
- 46.↑
Public Employees for Environmental Responsibility. Flea-control products found to be infested with forever chemicals. PEER; 2021. Accessed June 10, 2022. https://peer.org/flea-control-products-found-to-be-infested-with-forever-chemicals/
- 47.↑
Kauffman D. Analytical Report: Frontline Plus for Dogs. 2021. Accessed June 10, 2022. https://www.biologicaldiversity.org/campaigns/pesticides_reduction/pdfs/Pet-Products-Lab-Report.pdf?eType=EmailBlastContent&eId=bbf8be92-41fc-41e4-a005-357e2ec07065
- 48.↑
Franko J, Meade BJ, Frasch HF, Barbero AM, Anderson SE. Dermal penetration potential of perfluorooctanoic acid (PFOA) in human and mouse skin. J Toxicol Environ Health Part A. 2012;75(1):50–62. doi:10.1080/15287394.2011.615108
- 49.↑
Whitehead HD, Venier M, Wu Y, et al. Fluorinated Compounds in North American Cosmetics. Environ Sci & Technol Lett. 2021;8(7):538–544. doi:10.1021/acs.estlett.1c00240
- 50.↑
Wang M, Guo W, Gardner S, Petreas M, Park JS. Per- and polyfluoroalkyl substances in Northern California cats: temporal comparison and a possible link to cat hyperthyroidism. Environ Toxicol Chem. 2018;37(10):2523–2529. doi:10.1002/etc.4239
- 51.↑
You D, Chang X, Guo L, et al. Per- and polyfluoroalkyl substances (PFASs) in the blood of police and Beagle dogs from Harbin, China: concentrations and associations with hematological parameters. Chemosphere. 2022;299:134367. doi:10.1016/j.chemosphere.2022.134367
- 52.↑
Steenland K, Fletcher T, Stein CR, et al. Review: evolution of evidence on PFOA and health following the assessments of the C8 Science Panel. Environ Intl. 2020;145:106125. doi:10.1016/j.envint.2020.106125
- 53.↑
Gomis MI, Vestergren R, Borg D, Cousins IT. Comparing the toxic potency in vivo of long-chain perfluoroalkyl acids and fluorinated alternatives. Environ Intl. 2018;113:1–9. doi:10.1016/j.envint.2018.01.011
- 54.↑
Weiss JM, Jones B, Koekkoek J, Bignert A, Lamoree MH. Per-and polyfluoroalkyl substances (PFASs) in Swedish household dust and exposure of pet cats. Environ Sci Pollut Res. 2021;28(29):39001–39013. doi:10.1007/s11356-021-13343-5
- 55.↑
Gleason JA, Post GB, Fagliano JA. Associations of perfluorinated chemical serum concentrations and biomarkers of liver function and uric acid in the US population (NHANES), 2007–2010. Environ Res. 2015;136:8–14. doi:10.1016/j.envres.2014.10.004
- 56.↑
Lin CY, Lin LY, Chiang CK, et al. Investigation of the associations between low-dose serum perfluorinated chemicals and liver enzymes in US adults. Am J Gastroenterol. 2010;105(6):1354–63. doi:10.1038/ajg.2009.707
- 57.↑
Guo H, Wang J, Yao J, et al. Comparative hepatotoxicity of novel PFOA alternatives (perfluoropolyether carboxylic acids) on male mice. Environ Sci Tech. 2019;53(7):3929–3937. doi:10.1021/acs.est.9b00148
- 58.↑
Son H-Y, Kim S-H, Shin H-I, Bae HI, Yang J-H. Perfluorooctanoic acid-induced hepatic toxicity following 21-day oral exposure in mice. Arch Toxicol. 2008;82(4):239–246. doi:10.1007/s00204-007-0246-x
- 59.↑
Butenhoff JL, Olsen GW, Chang S. Toxicological response of Sprague Dawley rats from inhalation exposure to perfluorooctane sulfonyl fluoride (POSF). Toxicol Lett. 2017;271:38–49. doi:10.1016/j.toxlet.2017.02.017
- 60.↑
Winquist A, Steenland K. Perfluorooctanoic acid exposure and thyroid disease in community and worker cohorts. Epidemiology. 2014;25(2):255–264. doi:10.1097/ede.0000000000000040
- 61.↑
Knox SS, Jackson T, Frisbee SJ, Javins B, Ducatman AM. Perfluorocarbon exposure, gender and thyroid function in the C8 Health Project. J Toxicol Sci. 2011;36(4):403–410. doi:10.2131/jts.36.403
- 62.↑
Hamers T, Kortenkamp A, Scholze M, Molenaar D, Cenijn PH, Weiss JM. Transthyretin-binding activity of complex mixtures representing the composition of thyroid-hormone disrupting contaminants in house dust and human serum. Environ Health Perspect. 2020;128(1):17015. doi:10.1289/ehp5911
- 63.↑
Stratakis N, Rock S, La Merrill MA, et al. Prenatal exposure to persistent organic pollutants and childhood obesity: a systematic review and meta-analysis of human studies. Obes Rev. 2022;23(S1):e13383. doi:10.1111/obr.13383
- 64.↑
Barry V, Darrow LA, Klein M, Winquist A, Steenland K. Early life perfluorooctanoic acid (PFOA) exposure and overweight and obesity risk in adulthood in a community with elevated exposure. Environ Res. 2014;132:62–69. doi:10.1016/j.envres.2014.03.025
- 65.↑
Bloom MS, Commodore S, Ferguson PL, et al. Association between gestational PFAS exposure and Children’s adiposity in a diverse population. Environ Res. 2022;203:111820
- 66.↑
Loveless SE, Slezak B, Serex T, et al. Toxicological evaluation of sodium perfluorohexanoate. Toxicology. 2009;264(1):32–44. doi:10.1016/j.tox.2009.07.011
- 67.↑
Hundley S, Sarrif A, Kennedy G Jr. Absorption, distribution, and excretion of ammonium perfluorooctanoate (APFO) after oral administration to various species. Drug Chem Toxicol. 2006;29(2):137–145. doi:10.1080/01480540600561361
- 68.↑
Kudo N, Sakai A, Mitsumoto A, Hibino Y, Tsuda T, Kawashima Y. Tissue distribution and hepatic subcellular distribution of perfluorooctanoic acid at low dose are different from those at high dose in rats. Biol Pharm Bull. 2007;30(8):1535–1540. doi:10.1248/bpb.30.1535
- 69.↑
Numata J, Kowalczyk J, Adolphs J, et al. Toxicokinetics of seven perfluoroalkyl sulfonic and carboxylic acids in pigs fed a contaminated diet. J Agric Food Chem. 2014;62(28):6861–6870. doi:10.1021/jf405827u
- 70.↑
Hanhijärvi H, Ylinen M, Haaranen T, Nevalainen T. A proposed species difference in the renal excretion of perfluoro octanoic acid in the Beagle dog and rat. New Developments in Biosciences: Their Implications for Laboratory Animal Science. Springer; 1988:409–412.
- 71.↑
Olsen GW, Burris JM, Ehresman DJ, et al. Half-life of serum elimination of perfluorooctanesulfonate, perfluorohexanesulfonate, and perfluorooctanoate in retired fluorochemical production workers. Environ Health Perspect. 2007;115(9):1298–1305. doi:10.1289/ehp.10009
- 72.↑
Hinderliter PM, DeLorme MP, Kennedy GL. Perfluorooctanoic acid: relationship between repeated inhalation exposures and plasma PFOA concentration in the rat. Toxicology. 2006;222(1–2):80–85. doi:10.1016/j.tox.2006.01.029
- 73.↑
National Academies of Sciences, Engineering, and Medicine. Guidance on PFAS Exposure, Testing, and Clinical Follow-Up. National Academies of Sciences, Engineering, and Medicine; 2022.