A critical review of the application of polymer of low concern regulatory criteria to fluoropolymers II: Fluoroplastics and fluoroelastomers.

Fluoropolymers are a distinct class of per- and polyfluoroalkyl substances (PFAS), high molecular weight (MW) polymers with fluorine attached to their carbon-only backbone. Fluoropolymers possess a unique combination of properties and unmatched functional performance critical to the products and manufacturing processes they enable and are irreplaceable in many uses. Fluoropolymers have documented safety profiles; are thermally, biologically, and chemically stable, negligibly soluble in water, nonmobile, nonbioavailable, nonbioaccumulative, and nontoxic. Although fluoropolymers fit the PFAS structural definition, they have very different physical, chemical, environmental, and toxicological properties when compared with other PFAS. This study describes the composition, uses, performance properties, and functionalities of 14 fluoropolymers, including fluoroplastics and fluoroelastomers, and presents data to demonstrate that they satisfy the widely accepted polymer hazard assessment criteria to be considered polymers of low concern (PLC). The PLC criteria include physicochemical properties, such as molecular weight, which determine bioavailability and warn of potential hazard. Fluoropolymers are insoluble (e.g., water, octanol) solids too large to migrate into the cell membrane making them nonbioavailable, and therefore, of low concern from a human and environmental health standpoint. Further, the study results demonstrate that fluoropolymers are a distinct and different group of PFAS and should not be grouped with other PFAS for hazard assessment or regulatory purposes. When combined with an earlier publication by Henry et al., this study demonstrates that commercial fluoropolymers are available from the seven participating companies that meet the criteria to be considered PLC, which represent approximately 96% of the global commercial fluoropolymer market. Integr Environ Assess Manag 2023;19:326-354. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Identification and classification of commercially relevant per- and poly-fluoroalkyl substances (PFAS).

Per- and poly-fluoroalkyl substances (PFAS) are a universe of fluorinated organic substances with very different physical, chemical, and biological properties including polymers and non-polymers; solids, liquids, and gases. Commercial PFAS-based products have been used in a wide variety of industrial and consumer applications because they have unique performance properties of significant socioeconomic value. The PFAS definition has evolved and expanded over the years. Numerous lists of PFAS, some with thousands of entries, have been compiled, but none have clearly identified which of the substances are commercially relevant. This study is the first to use a bona-fide "bottom up" approach to identify how many of the 4730 PFAS substances listed in a 2018 OECD/UNEP Report are directly connected to commercial products based on input from three major global producers. This study provides new and valuable insight into the 2018 OECD/UNEP Report list of PFAS substances. The results show that 256, less than 6%, of the 4730 PFAS substances presented in the 2018 OECD/UNEP Report are commercially relevant globally. This study suggests that grouping and categorizing PFAS using fundamental classification criteria based on composition and structure can be used to identify appropriate groups of PFAS substances for risk assessment, thereby dispelling assertions that there are too many PFAS chemistries to conduct proper regulatory risk assessments for the commercially relevant substances. Integr Environ Assess Manag 2021;17:1045-1055. © 2021 The Chemours Company, Beach Edge Consulting, LLC, AGC Chemicals Americas Inc., Daikin America Inc. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Estimating Environmental Hazard and Risks from Exposure to Per- and Polyfluoroalkyl Substances (PFASs): Outcome of a SETAC Focused Topic Meeting.

Per- and polyfluoroalkyl substances (PFAS) are a group of highly fluorinated synthetic chemicals that were originally developed for uses as surfactants and surface protectors. Increasingly, specific substances of this class are being found in environmental media (e.g., surface water, soils, sediments, food sources), and concerns regarding exposure to humans and environmental receptors have been described by the public, legislators, and the general population. Data suggest that some PFAS (such as certain of the long-chain ones) bioaccumulate and have long biological half-lives, particularly in humans. Toxicity data in various organisms are variable as are their toxicokinetics. A Society of Environmental Toxicology and Chemistry (SETAC) Focused Topic Meeting and workshop entitled Environmental Risk Assessment of PFAS convened during 12 to 15 August, 2019 in Durham, North Carolina (USA) and brought together experts from around the globe to highlight recent advances in research pertinent to evaluating environmental and human health risks from exposures. The objectives of the Focused Topic Meeting and workshop were: 1) to review new and emerging information on PFAS chemical classification and grouping, environmental chemistry, detection technology, fate and transport, exposure potential, human health toxicity, and ecological toxicity; and 2) to harness the expertise of attendees to discuss and formulate a roadmap to prioritize the study of specific PFAS with the goal of developing a risk assessment approach that considers mechanistic (including computational) data for extrapolating exposure and data across different species/scenarios and compounds within environmental exposure pathways. We present the key issues that were discussed. Environ Toxicol Chem 2021;40:543-549. © 2020 SETAC.

A critical review of the application of polymer of low concern and regulatory criteria to fluoropolymers.

Per- and polyfluoroalkyl substances (PFAS) are a group of fluorinated substances that are in the focus of researchers and regulators due to widespread presence in the environment and biota, including humans, of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). Fluoropolymers, high molecular weight polymers, have unique properties that constitute a distinct class within the PFAS group. Fluoropolymers have thermal, chemical, photochemical, hydrolytic, oxidative, and biological stability. They have negligible residual monomer and oligomer content and low to no leachables. Fluoropolymers are practically insoluble in water and not subject to long-range transport. With a molecular weight well over 100 000 Da, fluoropolymers cannot cross the cell membrane. Fluoropolymers are not bioavailable or bioaccumulative, as evidenced by toxicology studies on polytetrafluoroethylene (PTFE): acute and subchronic systemic toxicity, irritation, sensitization, local toxicity on implantation, cytotoxicity, in vitro and in vivo genotoxicity, hemolysis, complement activation, and thrombogenicity. Clinical studies of patients receiving permanently implanted PTFE cardiovascular medical devices demonstrate no chronic toxicity or carcinogenicity and no reproductive, developmental, or endocrine toxicity. This paper brings together fluoropolymer toxicity data, human clinical data, and physical, chemical, thermal, and biological data for review and assessment to show that fluoropolymers satisfy widely accepted assessment criteria to be considered as "polymers of low concern" (PLC). This review concludes that fluoropolymers are distinctly different from other polymeric and nonpolymeric PFAS and should be separated from them for hazard assessment or regulatory purposes. Grouping fluoropolymers with all classes of PFAS for "read across" or structure-activity relationship assessment is not scientifically appropriate. Integr Environ Assess Manag 2018;14:316-334. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Biotransformation potential of 6:2 fluorotelomer sulfonate (6:2 FTSA) in aerobic and anaerobic sediment.

Aqueous film-forming foam (AFFF) products are used in industrial and military firefighting around the globe. These products contain fluoroalkylthioamido sulfonates, fluoroalkylthiobetaine, and other related substances as the major ingredients, which can be biotransformed in the environment to form 6:2 fluorotelomer sulfonate (6:2 FTSA, F(CF2)6CH2CH2SO3-) as one of the major initial biotransformation products. Limited information is available on 6:2 FTSA aerobic biotransformation in activated sludge and pure microbial culture. This is the first study to report 6:2 FTSA biotransformation in aerobic and anaerobic sediment. 6:2 FTSA was rapidly biotransformed in aerobic river sediment with a half-life less than 5 d. Major stable transformation products observed after 90 d included 5:3 Acid [F(CF2)5CH2CH2COOH), 16 mol%), PFPeA [F(CF2)4COOH, 21 mol%] and PFHxA (F(CF2)5COOH, 20 mol%). 6:2 fluorotelomer alcohol [6:2 FTOH, F(CF2)6CH2CH2OH] was readily biotransfomed whereas 6:2 FTSA biotransformation did not occur in anaerobic sediment over 100 d, indicating that the enzymatic desulfonation step limited 6:2 FTSA biotransformation in anaerobic sediment. These results suggest that 6:2 FTSA related products, after release to the aerobic environment, is likely to biodegrade forming 5:3 Acid, PFPeA and PFHxA. This study also indicates that 6:2 FTSA formed from its aforementioned precursors may be persistent in the anaerobic environment after their potential release. This work provides insight to understanding the fate and environmental loading of AFFF-related products and their major transformation products in the environment.

Aquatic hazard, bioaccumulation and screening risk assessment for ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate.

The fluoropolymer manufacturing industry is moving to alternative polymerization processing aid technologies with more favorable toxicological and environmental profiles as part of a commitment to curtail the use of long-chain perfluoroalkyl acids (PFAAs). To facilitate the environmental product stewardship assessment and premanufacture notification (PMN) process for a candidate replacement chemical, we conducted acute and chronic aquatic toxicity tests to evaluate the toxicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate (C6HF11O3.H3N) or the acid form of the substance to the cladoceran, Daphnia magna, the green alga, Pseudokirchneriella subcapitata, and a number of freshwater fish species including the rainbow trout, Oncorhynchus mykiss, In addition, testing with the common carp, Cyprinus carpio, was conducted to determine the bioconcentration potential of the acid form of the compound. Based on the relevant criteria in current regulatory frameworks, the results of the aquatic toxicity and bioconcentration studies indicate the substance is of low concern for aquatic hazard and bioconcentration in aquatic organisms. Evaluation of environmental monitoring data in conjunction with the predicted no effect concentration (PNEC) based on the available data suggest low risk to aquatic organisms.

Absorption, distribution, metabolism, excretion, and kinetics of 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)propanoic acid ammonium salt following a single dose in rat, mouse, and cynomolgus monkey.

Ammonium, 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate has been developed as a processing aid used in the manufacture of fluoropolymers. The absorption, distribution, elimination, and distribution (ADME) and kinetic behavior of this substance has been evaluated in rats, mice, and cynomolgus monkeys by oral and intravenous routes of exposure and studied in both plasma and urine. The test substance is rapidly and completely absorbed in both rats and mice and both in vivo and in vitro experiments indicate that it is not metabolized. The test substance is rapidly eliminated exclusively in the urine in both rats and mice, with rats eliminating it more quickly than mice (approximately 5h elimination half-life in rats, 20 h half-life in mice). Pharmacokinetic analysis in monkeys, rats, and mice indicate rapid, biphasic elimination characterized by a very fast alpha phase and a slower beta phase. The beta phase does not contribute to potential accumulation after multiple dosing in rats or monkeys. Comparative pharmacokinetics in rats, mice, and monkeys indicates that the rat is more similar to the monkey and is therefore a more appropriate rodent model for pharmacokinetics in primates.

Aquatic hazard, bioaccumulation and screening risk assessment for 6:2 fluorotelomer sulfonate.

This study assessed the aquatic toxicity and bioaccumulation potential of 6:2 fluorotelomer sulfonate (6:2 FTSA). Acute and chronic aquatic hazard endpoints indicate 6:2 FTSA is not classified for aquatic hazard according to GHS or European CLP legislation. The aqueous bioconcentration factors for 6:2 FTSA were <40 and the dietary assimilation efficiency, growth corrected half-life and dietary biomagnification factor (BMF) were 0.435, 23.1d and 0.295, respectively. These data indicate that 6:2 FTSA is not bioaccumulative in aquatic organisms. Comparison of PNECs with the reported surface water concentrations (non-spill situations) suggests low risk to aquatic organisms from 6:2 FTSA. Future studies are needed to elucidate the biotic and abiotic fate of commercial AFFF surfactants in the environment.

Oral repeated-dose systemic and reproductive toxicity of 6:2 fluorotelomer alcohol in mice.

6:2 fluorotelomer alcohol (6:2 FTOH) was evaluated for potential systemic repeated-dose and reproductive toxicity in mice. 6:2 FTOH was administered by oral gavage to CD-1 mice as a suspension in 0.5% aqueous methylcellulose with 0.1% Tween-80 at dosages of 1, 5, 25, or 100 mg/kg/day. The no-observed-adverse-effect level (NOAEL) for systemic toxicity was 25 mg/kg/day (males) and 5 mg/kg/day (females), based on effects at higher doses on mortality, clinical observations, body weight, nutritional parameters, hematology (red and white blood cell), clinical chemistry (liver-related), liver weights, and histopathology (liver, teeth, reproductive tract, and mammary gland). However, 6:2 FTOH was not a selective reproductive toxicant. The NOAEL for reproductive toxicity was >100 mg/kg/day; no effects on reproductive outcome were observed at any dosage. The NOAEL for viability and growth of the offspring was 25 mg/kg/day, based on clinical signs of delayed maturation in pups, and reductions in pup survival and pup body weight during lactation at 100 mg/kg/day. While the severity of the effects was generally greater in mice than previously reported in CD rats, the overall NOAELs were identical in both species, 5 mg/kg/day for systemic toxicity and 25 mg/kg/day for offspring viability/growth. 6:2 FTOH was not a selective reproductive toxicant in either species; no effects on reproductive outcome occurred at any dose level, and any effects observed in offspring occurred at dose levels that induced mortality and severe toxicity in maternal animals.

Inhalation and oral toxicokinetics of 6:2 FTOH and its metabolites in mammals.

The toxicokinetics of 6:2 fluorotelomer alcohol (6:2 FTOH) and its terminal perfluorinated and polyfluorinated metabolites (PFBA, PFHxA, PFHpA and 5:3 Acid) have been calculated from laboratory studies of rats and from a biomonitoring study of humans. In vitro studies with mouse, rat and human hepatocytes indicate qualitatively similar metabolic pathways of 6:2 FTOH. In a one-day inhalation study of 6:2 FTOH in rats, PFBA, PFHxA, PFHpA and 5:3 Acid were determined to be the major metabolites in plasma with calculated elimination half-lives of 1.3-15.4h and metabolic yields up to 2.7 mol%. In five-day and 23-day inhalation studies and a 90-day oral study of 6:2 FTOH, the plasma or serum concentration profile of 5:3 Acid was several-fold higher than concentrations observed in the single day study, resulting in an estimated elimination half-life of 20-30 d. In contrast, the concentrations of PFBA, PFHxA and PFHpA showed little or no concentration increase with repeated exposure. Elimination half-lives of PFHxA, PFHpA and 5:3 Acid in humans were estimated from a study of professional ski wax technicians who were occupationally exposed to aerosolized and volatilized components of fluorinated glide wax. The resulting human elimination half-life values of PFHxA, PFHpA and 5:3 Acid were 32, 70 and 43 d, respectively. Based on a one compartment toxicokinetic model, current environmental air concentrations of 6:2 FTOH are estimated to result in plasma concentrations of PFHxA, PFHpA and 5:3 Acid that are less than or equal to typical LOQ values, in agreement with extant biomonitoring results.

6:2 Fluorotelomer iodide in vitro metabolism by rat liver microsomes: comparison with [1,2-(14)C] 6:2 fluorotelomer alcohol.

6:2 Fluorotelomer iodide [6:2 FTI, F(CF2)6CH2CH2I] is the industrial raw material used to manufacture 6:2 fluorotelomer alcohol [6:2 FTOH, F(CF2)6CH2CH2OH] and 6:2 FTOH-based products. During its manufacture and industrial use, workers may be exposed to via oral, dermal or inhalation of 6:2 FTI. Therefore it is useful to understand how 6:2 FTI may be metabolized and into what transformation products. 6:2 FTI in vitro rat liver microsomal metabolism was explored for the first time to compare its biotransformation potential with that of [1,2-(14)C] 6:2 FTOH [F(CF2)6(14)CH2(14)CH2OH]. 6:2 FTI and 6:2 FTOH metabolite yields were determined in closed-bottle systems using Sprague Dawley and Wistar Han rat microsomes after incubation at 37 °C for up to 6h with NADPH (reduced form of nicotinamide adenine dinucleotide phosphate)-addition and NADPH-regenerating systems, respectively. 5:3 acid [F(CF2)5CH2CH2COOH] was the most abundant metabolite for 6:2 FTI (3.3-6.3 mol%) and 6:2 FTOH (9-12 mol%). Perfluorobutanoic acid (PFBA), perfluoropentanoic acid (PFPeA), and perfluorohexanoic acid (PFHxA) in sum accounted for 1.3-2.2 mol% from 6:2 FTI and 2.7-4.4 mol% from 6:2 FTOH biotransformation. Perfluoroheptanoic acid (PFHpA) accounted for 0.14-0.36 mol% from 6:2 FTI but only 0.01-0.06 mol% from 6:2 FTOH biotransformation. These results suggest that mammalian systems exposed to 6:2 FTI or 6:2 FTOH would form 5:3 acid, PFBA, PFPeA, PFHxA as the primary stable metabolites, whereas more PFHpA would be expected from 6:2 FTI biotransformation.

Global emission inventories for C4-C14 perfluoroalkyl carboxylic acid (PFCA) homologues from 1951 to 2030, Part I: production and emissions from quantifiable sources.

We quantify global emissions of C4-C14 perfluoroalkyl carboxylic acid (PFCA) homologues during the life-cycle of products based on perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorooctane sulfonyl fluoride (POSF), and fluorotelomer compounds. We estimate emissions of 2610-21400 tonnes of C4-C14 PFCAs in the period from 1951 to 2015, and project 20-6420 tonnes to be emitted from 2016 to 2030. The global annual emissions steadily increased in the period 1951-2002, followed by a decrease and then another increase in the period 2002-2012. Releases from fluoropolymer production contributed most to historical PFCA emissions (e.g. 55-83% in 1951-2002). Since 2002, there has been a geographical shift of industrial sources (particularly fluoropolymer production sites) from North America, Europe and Japan to emerging Asian economies, especially China. Sources differ between PFCA homologues, sometimes considerably, and the relative contributions of each source change over time. For example, whereas 98-100% of historical (1951-2002) PFOA emissions are attributed to direct releases during the life-cycle of products containing PFOA as ingredients or impurities, a much higher historical contribution from PFCA precursor degradation is estimated for some other homologues (e.g. 9-78% for PFDA). We address the uncertainties of the PFCA emissions by defining a lower and a higher emission scenario, which differ by approximately a factor of eight.

Global emission inventories for C4-C14 perfluoroalkyl carboxylic acid (PFCA) homologues from 1951 to 2030, part II: the remaining pieces of the puzzle.

We identify eleven emission sources of perfluoroalkyl carboxylic acids (PFCAs) that have not been discussed in the past. These sources can be divided into three groups: [i] PFCAs released as ingredients or impurities, e.g., historical and current use of perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA) and their derivatives; [ii] PFCAs formed as degradation products, e.g., atmospheric degradation of some hydrofluorocarbons (HFCs) and hydrofluoroethers (HFEs); and [iii] sources from which PFCAs are released as both impurities and degradation products, e.g., historical and current use of perfluorobutane sulfonyl fluoride (PBSF)- and perfluorohexane sulfonyl fluoride (PHxSF)-based products. Available information confirms that these sources were active in the past or are still active today, but due to a lack of information, it is not yet possible to quantify emissions from these sources. However, our review of the available information on these sources shows that some of the sources may have been significant in the past (e.g., the historical use of PFBA-, PFHxA-, PBSF- and PHxSF-based products), whereas others can be significant in the long-term (e.g., (bio)degradation of various side-chain fluorinated polymers where PFCA precursors are chemically bound to the backbone). In addition, we summarize critical knowledge and data gaps regarding these sources as a basis for future research.

Toxicological evaluation of 6:2 fluorotelomer alcohol.

6:2 fluorotelomer alcohol (6:2 FTOH; CF3[CF2]5[CH2]2OH, CAS# 647-42-7) was evaluated for acute, genetic, and subchronic toxicity using in vitro and in vivo methods. In rats, 6:2 FTOH was considered to be slightly toxic by the oral (LD50=1,750 mg/kg), and dermal (LD50 > 5,000 mg/kg) routes. In rabbits, 6:2 FTOH was not a primary skin or eye irritant, and it did not produce a dermal sensitization response in mice. In a 90-day subchronic study, 6:2 FTOH was administered to rats by oral gavage (0, 5, 25, 125, 250 mg/kg/day). Mortality was observed at 125 and 250 mg/kg/day; deaths occurred after approximately three weeks of dosing and continued sporadically. The NOAEL in the subchronic study was 5mg/kg/day based on hematology and liver effects. 6:2 FTOH was not mutagenic in the bacterial reverse mutation test or in the mouse lymphoma assay and was not clastogenic in a chromosome aberration assay in human lymphocytes. The hazard classification for human health endpoints of 6:2 FTOH according to the United Nations Globally Harmonized System of Classification and Labeling of Chemicals (GHS) is Category 4 for acute oral toxicity based on an LD50 of 1,750 mg/kg. Other acute health endpoints including eye and skin irritation, skin sensitization, as well as genotoxicity, did not meet the criteria for hazard classification. Benchmark Dose Analysis was performed on the most sensitive endpoints from the 90-day oral gavage study and these levels were all above the study NOAEL of 5mg/kg/day. For risk assessment purposes, the recommended point of departure is the more conservative study NOAEL of 5mg/kg/day.

Evaluation of the reproductive and developmental toxicity of 6:2 fluorotelomer alcohol in rats.

6:2 Fluorotelomer alcohol (6:2 FTOH) was evaluated for potential developmental and reproductive toxicity. 6:2 FTOH was administered by oral gavage to Sprague-Dawley rats as a suspension in 0.5% aqueous methylcellulose at dosages of 5, 25, 125, or 250 mg/kg/day. The developmental toxicity study was performed in accordance with the Organization for Economic Development (OECD) Test Guideline 414, and the one-generation reproductive toxicity study was performed in accordance with the OECD Test Guideline 415. For the developmental toxicity study, adverse maternal toxicity observed at 250 mg/kg/day included reductions in body weight parameters and food consumption. Evidence of developmental toxicity was limited to increases in skeletal variations (ossification delays in the skull and rib alterations) at 250 mg/kg/day. There were no adverse maternal or developmental effects observed at 5, 25, or 125 mg/kg/day and there were no effects on reproductive outcome or quantitative litter data at any dose level. For the one-generation reproduction toxicity study, systemic parental and developmental toxicity were observed at 125 and 250 mg/kg/day. At 250 mg/kg/day, there was increased mortality among male and female parental rats, effects on body weight parameters, food consumption, and clinical signs, and there were effects on offspring survival indices and body weights. At 125 mg/kg/day, there was an increase in mortality in parental males only, and parental toxicity was limited to effects on body weight gain, food consumption (lactation), and clinical signs. Uterine weights were decreased at 125 and 250 mg/kg/day, although there were no corroborative histopathological changes. At 125 mg/kg/day, pup mortality was increased on lactation day 1, and body weights of the offspring were decreased during the second half of lactation. There was no evidence of either parental or developmental toxicity at 5 or 25mg/kg/day, and there were no effects on reproductive outcome at any dose level. Based on these data, 6:2 FTOH is not a selective reproductive or developmental toxicant at dosages that induce clear maternal/parental toxicity. Therefore, 6:2 FTOH would not be classified for reproductive/developmental toxicity under the United Nations' Globally Harmonized System of Classification and Labeling of Chemicals.

Aerobic soil biotransformation of 6:2 fluorotelomer iodide.

6:2 FTI [F(CF2)6CH2CH2I] is a principal industrial raw material used to manufacture 6:2 FTOH [F(CF2)6CH2CH2OH] and 6:2 FTOH-based products and could enter aerobic environments from possible industrial emissions where it is manufactured. This is the first study to assess 6:2 FTI aerobic soil biotransformation, quantify transformation products, and elucidate its biotransformation pathways. 6:2 FTI biotransformation led to 6:2 FTOH as a key intermediate, which was subsequently biotransformed to other significant transformation products, including PFPeA [F(CF2)4COOH, 20 mol % at day 91], 5:3 acid [F(CF2)5CH2CH2COOH, 16 mol %], PFHxA [F(CF2)5COOH, 3.8 mol %], and 4:3 acid [F(CF2)4CH2CH2COOH, 3.0 mol %]. 6:2 FTI biotransformation also led to a significant level of PFHpA [F(CF2)6COOH, 16 mol % at day 91], perhaps via another putative intermediate, 6:2 FTUI [F(CF2)6CH ═ CHI], whose molecular identity and further biotransformation were not verified because of the lack of an authentic standard. Total recovery of the aforementioned per- and polyfluorocarboxylates accounted for 59 mol % of initially applied 6:2 FTI by day 91, in comparison to 56 mol % when soil was dosed with 6:2 FTOH, which did not lead to PFHpA. Thus, were 6:2 FTI to be released from its manufacture and undergo soil microbial biotransformation, it could form PFPeA, PFHpA, PFHxA, 5:3 acid, and 4:3 acid in the environment.

Elimination kinetics of perfluorohexanoic acid in humans and comparison with mouse, rat and monkey.

Major fluorinated chemical manufacturers have developed new short-chain per- and polyfluorinated substances with more favorable environmental, health and safety profiles. This study provides the first evaluation of the elimination half-life of perfluorohexanoic acid (PFHxA) from the blood of humans. PFHxA biomonitoring data were obtained from a recently published study of professional ski wax technicians. These data were analyzed to provide estimates of the apparent half-life of PFHxA from humans, and comparisons were made with kinetic studies of PFHxA elimination from mice, rats and monkeys. The apparent elimination half-life of PFHxA in highly exposed humans ranged between 14 and 49 d with a geomean of 32 d. The half-lives of PFHxA in mice, rats, monkeys and humans were proportional to body weight with no differences observed between genders, indicating similar volumes of distribution and similar elimination mechanisms among mammalian species. Compared to long-chain perfluoroalkyl acid analogs, PFHxA is rapidly cleared from biota. The consistent weight-normalized elimination half-lives for PFHxA in mammalian species indicates that results obtained from animal models are suitable for establishment of PFHxA benchmark dose and reference dose hazard endpoints for use in human risk assessments.

6:2 Fluorotelomer alcohol aerobic biotransformation in activated sludge from two domestic wastewater treatment plants.

6:2 Fluorotelomer alcohol [6:2 FTOH, F(CF2)6CH2CH2OH] is a major basic chemical being used to manufacture FTOH-based products. After the end of use, 6:2 FTOH-based products may be released to domestic wastewater treatment plants (WWTPs) as a first major environmental entry point. Activated sludge collected from two WWTPs was dosed with 6:2 FTOH to investigate its biotransformation rate and to identify major transformation products. The volatile 5:2 sFTOH [F(CF2)5CH(OH)CH3] is the most abundant transformation product and accounted for an average of 40mol% of initially dosed 6:2 FTOH after two months of incubation with activated sludge, with 30mol% detected in the headspace. PFPeA [F(CF2)4COOH] averaged 4.4mol% after two months, 2.4-7 times lower than that in sediment and soils. The much lower level of PFPeA formed in activated sludge compared with soil indicates that microbial populations in activated sludge may lack enzymes or suitable environment conditions to promote rapid 5:2 sFTOH decarboxylation to form PFPeA, resulting in more 5:2 sFTOH partitioned to the headspace. PFHxA [F(CF2)5COOH] and 5:3 [F(CF2)5CH2CH2COOH] acid are major non-volatile transformation products in activated sludge. For example, PFHxA averaged 11mol% after two months, which is about 30% higher compared with sediment and soils, suggesting that microbes in WWTPs may utilize similar pathways as that in sediment and soils to convert 5:2 sFTOH to PFHxA. 5:3 Acid averaged 14mol% after two months, comparable to that in soils and slightly lower than in sediment, further confirming that 5:3 acid is a unique product of 6:2 FTOH biotransformation in the environment.

6:2 and 8:2 fluorotelomer alcohol anaerobic biotransformation in digester sludge from a WWTP under methanogenic conditions.

6:2 FTOH and 8:2 FTOH [FTOHs, F(CF2)nCH2CH2OH, n = 6, 8] are the principal polyfluorinated raw materials used to manufacture FTOH-based products, which may be released to WWTPs during their product life cycle. For the first time, anaerobic biotransformation of FTOHs and key biotransformation intermediates in WWTP digester sludge under methanogenic conditions was investigated. 6:2 FTOH was transformed to 6:2 FTCA, [F(CF2)6CH2COOH, 32-43 mol %], 6:2 FTUCA [F(CF2)5CF═CHCOOH, 1.8-8.0 mol %], and 5:3 acid [F(CF2)5CH2CH2COOH, 18-23 mol %] by day 90 and day 176 in two separate studies. 8:2 FTOH was transformed by day 181 to 8:2 FTCA (18 mol %), 8:2 FTUCA (5.1 mol %), and 7:3 acid (27 mol %). 6:2 and 8:2 FTOH anaerobic biotransformation led to low levels of perfluorohexanoic acid (PFHxA, ≤0.4 mol %) and perfluorooctanoic acid (PFOA, 0.3 mol %), respectively. 6:2 FTUCA anaerobic biotransformation led to a newly identified novel transient intermediate 3-fluoro 5:3 acid [F(CF2)5CFHCH2COOH] and 5:3 acid, but not 5:2 sFTOH [F(CF2)5CH(OH)CH3] and α-OH 5:3 acid [F(CF2)5CH2CH(OH)COOH], two precursors leading to PFPeA (perfluoropentanoic acid) and PFHxA. Thus, FTOH anaerobic biotransformation pathways operated by microbes in the environment was likely inefficient at shortening carbon chains of FTOHs to form PFCAs (perfluorinated carboxylic acids). These results imply that anaerobic biotransformation of FTOH-based products may produce polyfluorinated acids, but is not likely a major source of PFCAs detected in anaerobic environmental matrices such as anaerobic digester sludge, landfill leachate, and anaerobic sediment under methanogenic conditions.

6:2 fluorotelomer alcohol biotransformation in an aerobic river sediment system.

The 6:2 FTOH [F(CF(2))(6)CH(2)CH(2)OH] is a major raw material being used to replace 8:2 FTOH [F(CF(2))(8)CH(2)CH(2)OH] to make FTOH-based products for industrial and consumer applications. A novel aerobic sediment experimental system containing 20 g wet sediment and 30 mL aqueous solution was developed to study 6:2 FTOH biotransformation in river sediment. 6:2 FTOH was dosed into the sediment to follow its biotransformation and to analyze transformation products over 100 d. The primary 6:2 FTOH biotransformation in the aerobic sediment system was rapid (T(1/2)<2d). 5:3 acid [F(CF(2))(5)CH(2)CH(2)COOH] was observed as the predominant polyfluorinated acid on day 100 (22.4 mol%), higher than the sum of perfluoropentanoic acid (10.4 mol%), perfluorohexanoic acid (8.4 mol%), and perfluorobutanoic acid (1.5 mol%). Perfluoroheptanoic acid was not observed during 6:2 FTOH biotransformation. The 5:3 acid can be further degraded to 4:3 acid [F(CF(2))(4)CH(2)CH(2)COOH, 2.7 mol%]. This suggests that microbes in the river sediment selectively degraded 6:2 FTOH more toward 5:3 and 4:3 acids compared with soil. Most of the observed 5:3 acid formed bound residues with sediment organic components and can only be quantitatively recovered by post-treatment with NaOH and ENVI-Carb™ carbon. The 6:2 FTCA [F(CF(2))(6)CH(2)COOH], 6:2 FTUCA [F(CF(2))(5)CF=CHCOOH], 5:2 ketone [F(CF(2))(5)C(O)CH(3)], and 5:2 sFTOH [F(CF(2))(5)CH(OH)CH(3)] were major transient intermediates during 6:2 FTOH biotransformation in the sediment system. These results suggest that if 6:2 FTOH or 6:2 FTOH-based materials were released to the river or marine sediment, poly- and per-fluorinated carboxylates could be produced.