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).

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.

Evaluation of chronic toxicity and carcinogenicity of ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate in Sprague-Dawley rats.

Ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate, developed for use as a polymerization processing aid in the manufacture of fluoropolymers, was tested for its potential chronic toxicity and carcinogenicity in a 2-year oral dosing study in Sprague-Dawley rats. Male rats were given daily doses of either 0, 0.1, 1 or 50 mg/kg; females were given either 0, 1, 50 or 500 mg/kg. Body weights, food consumption and clinical signs were monitored daily; clinical pathology was conducted at designated intervals and animals were given a complete pathological evaluation after 12 months and 24 months of dosing. Normal survival was seen in all groups, no abnormal clinical signs were seen, and body weight gain was reduced only in female rats at 500 mg/kg. Both sexes at the high dose had mild decreases in red cell mass which were somewhat more pronounced in females. Clinical pathology indicative of liver injury was present in males that received 50 mg/kg and correlated with histomorphological liver changes that included both hypertrophic and degenerative/necrotic lesions. Similar histomorphological lesions were seen in the livers of females at 500 mg/kg. Previous shorter term toxicity studies have identified this chemical as a PPARα agonist and the finding of benign tumors of the liver, pancreas and/or testes in males at 50 mg/kg and females at 500 mg/kg is consistent with the rat response to peroxisome proliferators and is of questionable human relevance. Changes in the kidney, tongue, and stomach were observed only at the highest dose of 500 mg/kg in females. The no-observed-adverse-effect-level in this study lies between 1 and 50 mg/kg for males and between 50 and 500 mg/kg for females.

Efficient "total" extraction of perfluorooctanoate from polytetrafluoroethylene fluoropolymer.

To determine the optimum conditions for the complete extraction of perfluorooctanoate (PFO) from polytetrafluoroethylene fluoropolymers, sample preparation and pressurized solvent extraction (PSE) conditions were investigated. Solvent extraction temperature, solvent residence time, relaxation time between extractions, and the effects of heating before PSE showed that methanol at 150 degrees C extraction temperature and a 12 min solvent residence time were the most efficient conditions. Preheating the polymer before extraction at 150 degrees C for 24 h significantly enhanced the quantity of PFO removed. Heating above 150 degrees C resulted in loss of PFO. PFO was determined by liquid chromatography with tandem mass spectrometry.

Vapor pressure determinations of 8-2 fluorortelomer alcohol and 1-H perfluorooctane by capillary gas chromatography Relative retention time versus headspace methods.

Two distinctly different capillary gas chromatographic methods were used to determine the vapor pressure of 8-2 fluorotelomer alcohol (8-2 FTOH) and 1-H perfluoroheptane at several temperatures. For measurements employing the relative retention-time method, a short polymethylsiloxane column was used from 25 to 65 degrees C. For the 8-2 FTOH, hydrocarbon alcohols and perfluoroalcohols were used as reference standards. For 1-H perfluoroheptane, hydrocarbons were used as reference standards. Vapor pressure estimates could differ by as much as an order of magnitude compared to published results determined by other (nonchromatographic) methods. This variance may be a function of solvent-solute interactions within the gas chromatographic column and the infinite dilution assumption, both used in the relative retention method. For comparison, data were also gathered using headspace gas chromatography (GC) with atomic emission detection (AED). The results from this novel GC/AED method were consistent with prior nonchromatographic results. A discussion of why headspace is the preferred technique for the determination of vapor pressure for fluorinated compounds is presented.

Determination of perfluorooctanoic acid (PFOA) extractable from the surface of commercial cookware under simulated cooking conditions by LC/MS/MS.

Salts of pentadecafluorooctanoic acid (PFOA) are polymerization aids used in the manufacture of fluoropolymers; one of the applications of fluoropolymers is the coating of metal cookware products. A method was developed to determine if PFOA might be present in and extracted from the surface of commercial frying pans coated with a DuPont fluoropolymer under simulated cooking conditions. Commercial grade cookware was obtained, then extracted with water and ethanol/water mixtures at 100 and 125 degrees C, and the resulting extracts were analyzed by liquid chromatography tandem mass spectrometry (LC/MS/MS). Detection and quantification limits as low as 100 pg cm(-2) were demonstrated. None of the fluoropolymer treated cookware samples analyzed showed detectable levels of PFOA when extracted under simulated cooking conditions.

Exposure assessment and risk characterization for perfluorooctanoate in selected consumer articles.

An exposure assessment and risk characterization was conducted to better understand the potential human health significance of trace levels of perfluorooctanoate (PFO) detected in certain consumer articles. PFO is the anion of perfluorooctanoic acid (PFOA). Concentrations of PFO in the consumer articles were determined from extraction tests and product formulation information. Potential exposures during consumer use of the articles were quantified based on an assessment of behavior patterns and regulatory guidance. Health benchmarks were developed and then compared to the exposure estimates to yield margins of exposure (MOEs). A simple one-compartment model was also developed to estimate contributions of potential consumer exposures to PFO concentrations in serum. While there are considerable uncertainties in this assessment, it indicates that exposures to PFO during consumer use of the articles evaluated in this study are not expected to cause adverse human health effects in infants, children, adolescents, adult residents, or professionals nor result in quantifiable levels of PFO in human serum.

Comparison of pressurized solvent and reflux extraction methods for the determination of perfluorooctanoic acid in polytetrafluoroethylene polymers using LC-MS-MS.

Both pressurized solvent extraction (PSE) and reflux extraction in various solvents were used to select the most efficient system for the determination of the quantity of perfluorooctanoic acid (PFOA) present in polytetrafluoroethylene polymers. After evaporating the solvent, PFOA was determined using liquid chromatography tandem mass spectrometry. Ethanol, water and methanol gave comparable results and were shown to be good solvents for this extraction. Acetonitrile was a reasonable solvent using the reflux extraction method, but not with PSE. Chloroform resulted in poor recovery for both extraction methods. PSE proved to be the more efficient extraction method.