Scott A. Mabury

Perfluoroalkyl and polyfluoroalkyl substances in the environment: Terminology, classification, and origins

The primary aim of this article is to provide an overview of perfluoroalkyl and polyfluoroalkyl substances (PFASs) detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFASs. The overarching objective is to unify and harmonize communication on PFASs by offering terminology for use by the global scientific, regulatory, and industrial communities. A particular emphasis is placed on long-chain perfluoroalkyl acids, substances related to the long-chain perfluoroalkyl acids, and substances intended as alternatives to the use of the long-chain perfluoroalkyl acids or their precursors. First, we define PFASs, classify them into various families, and recommend a pragmatic set of common names and acronyms for both the families and their individual members. Terminology related to fluorinated polymers is an important aspect of our classification. Second, we provide a brief description of the 2 main production processes, electrochemical fluorination and telomerization, used for introducing perfluoroalkyl moieties into organic compounds, and we specify the types of byproducts (isomers and homologues) likely to arise in these processes. Third, we show how the principal families of PFASs are interrelated as industrial, environmental, or metabolic precursors or transformation products of one another. We pay particular attention to those PFASs that have the potential to be converted, by abiotic or biotic environmental processes or by human metabolism, into long-chain perfluoroalkyl carboxylic or sulfonic acids, which are currently the focus of regulatory action. The Supplemental Data lists 42 families and subfamilies of PFASs and 268 selected individual compounds, providing recommended names and acronyms, and structural formulas, as well as Chemical Abstracts Service registry numbers. Integr Environ Assess Manag 2011;7:513–541.

Photodegradation of the pharmaceuticals atorvastatin, carbamazepine, levofloxacin, and sulfamethoxazole in natural waters

Abstract.The photochemical behaviour of the four pharmaceuticals, atorvastatin, carbamazepine, levofloxacin, and sulfamethoxazole in sunlit surface water was investigated. These compounds, which have been observed or have the potential to be in surface waters, were susceptible to direct and indirect photodegradation. Several photoproducts are identified using authentic standards, and structures of other degradation products are proposed based on mass spectral information from this and previous studies. The same degradation compounds are formed from direct and indirect photolysis, suggesting the same photoproducts are formed by alternate pathways. The natural water constituents nitrate, dissolved organic matter (DOM), and bicarbonate influence the elimination rates of the pharmaceuticals differently. Since direct photolysis appears important in limiting the persistence of levofloxacin and sulfamethoxazole, the presence of humic matter decreases degradation rates. The same constituent has an opposite and positive effect on the elimination rates of atorvastatin and carbamazepine and thus, photosensitization reactions or photooxidants generated from DOM photolysis are important. Products resulting from direct and indirect photolysis also seem to be susceptible to photodegradation, suggesting they will not persist in sunlit aqueous systems.

Aquatic persistence of eight pharmaceuticals in a microcosm study

The persistence of eight pharmaceuticals from multiple classes was studied in aquatic outdoor field microcosms. A method was developed for the determination of a mixture of acetaminophen, atorvastatin, caffeine, carbamazepine, levofloxacin, sertraline, sulfamethoxazole, and trimethoprim at microg/L levels from surface water of the microcosms using solid phase extraction and high-performance liquid chromatography-ultraviolet (HPLC-UV) and liquid chromatography tandem mass spectrometry (LC-MS-MS). Half-lives in the field ranged from 1.5 to 82 d. Laboratory persistence tests were performed to determine the relative importance of possible loss processes in the microcosms over the course of the study. Results from dark control experiments suggest hydrolysis was not important in the loss of the compounds. No significant differences were observed between measured half-lives of the pharmaceuticals in sunlight-exposed pond water and autoclaved pond water, which suggests photodegradation was important in limiting their persistence, and biodegradation was not an important loss process in surface water over the duration of the study. Observed photoproducts of several of the pharmaceuticals remained photoreactive, which led to further degradation in irradiated surface waters.

Is indirect exposure a significant contributor to the burden of perfluorinated acids observed in humans

In comparison to other persistent organic pollutants, human fluorochemical contamination is relatively complicated. This complication arises at least in part from a disparity between the chemicals used commercially and those measured in the environment and humans. Commercial fluorochemical products are dominated by fluorinated polymers used in textile or carpet applications, or fluorosurfactants used in applications ranging from personal care products, leveling and wetting agents, to greaseproofing food-contact materials. Investigations into environmental and human fluorochemical contamination have focused on perfluorinated acids (PFAs), either the perfluorinated carboxylates (PFCAs) or sulfonates (PFSAs). In this review we will present an overview of data related to human fluorochemical exposure including a discussion of fluorochemical production, concentrations in exposure media, biotransformation processes producing PFAs, and trends in human sera. These data will be presented in the context of how they can inform sources of human PFA contamination, specifically whether the contamination results from direct PFA exposure or indirect exposure via the biotransformation of commercial fluorochemicals or their residuals. Concentrations of both perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) began to decrease in human sera around the year 2000, a change that mirrored the 2000-2002 phase-out of perfluorooctane sulfonyl fluoride (POSF) production. These temporal trends suggest exposure to current-use POSF-based materials was a significant source of PFOA and PFOS exposure prior to 2000. Relatively slow PFOA elimination and increasing concentrations of the C9 and C10 PFCAs in human sera suggest continued PFCA exposure, without similar exposure to PFOS, which is consistent with indirect exposure via the biotransformation of fluorotelomer-based materials. Conversely, human exposure models have suggested direct exposure to PFAs present in food items is the major source of human contamination. The data set presented here cannot unequivocally delineate between direct and indirect human exposure, however temporal trends in human sera and exposure media are consistent with indirect exposure representing a significant portion of observed human PFA contamination.

Biodegradation of Polyfluoroalkyl Phosphates as a Source of Perfluorinated Acids to the Environment

Wastewater treatment plants (WWTPs) have been identified as a major source of perfluorocarboxylates (PFCAs) to aqueous environments. The observed increase in PFCA mass flows from WWTP influent to effluent suggests the biodegradation of commercial fluorinated materials within the WWTP. Commercial fluorinated surfactants are used as greaseproofing agents in food-contact paper products as well as leveling and wetting agents. As WWTPs are likely the major fate of these surfactants, their biodegradation may be a source of PFCA production. One class of commercial surfactants, the polyfluoroalkyl phosphates (PAPs), have been observed in WWTP sludge. While PAPs have been shown to degrade into PFCAs in a rat model, the present study investigates their microbial fate to determine whether the biodegradation of PAPs within a WWTP-simulated system will contribute to the load of PFCAs released. PAPs are applied commercially in mixed formulations of different chain lengths and substitution at the phosphate center. The effect of chain length and phosphate substitution on the biodegradation of PAPs was investigated by incubating mixtures of 4:2, 6:2, 8:2, and 10:2 monosubstituted PAPs (monoPAPs) in an aerobic microbial system and by separately incubating the 6:2 monoPAP and 6:2 disubstituted PAP (diPAP) for 92 days. Headspace sampling revealed production of the fluorotelomer alcohols (FTOHs) from the hydrolysis of the PAP phosphate ester linkages. Analysis of the aqueous phase revealed microbial transformation of the PAPs to the final PFCA products was possible. The majority of the oxidation products observed were consistent with previous investigations that have suggested fluorotelomer precursor compounds degrade predominantly via a beta-oxidation-like mechanism. However, in this study, the detection of odd-chain PFCAs suggests that other pathways may be important. The present study demonstrated microbially mediated biodegradation of PAPs to PFCAs. This observation, together with the diPAP concentrations observed in WWTP sludge, suggest PAPs-containing commercial products may be a significant contributor to the increased PFCA mass flows observed in WWTP effluents.

Effects of pharmaceutical mixtures in aquatic microcosms.

Pharmaceuticals have a wide range of biological properties and are released into the environment in relatively large amounts, yet little information is available regarding their effects or potential ecological risks. We exposed outdoor aquatic microcosms to combinations of ibuprofen (a nonsteroidal anti-inflammatory drug), fluoxetine (a selective serotonin reuptake inhibitor), and ciprofloxacin (a DNA gyrase-inhibiting antibiotic) at concentrations of 6, 10, and 10 microg/L, respectively (low treatment [LT]); 60, 100, and 100 microg/L, respectively (medium treatment [MT]); and 600, 1,000, and 1,000 microg/L, respectively (high treatment [HT]). We maintained these concentrations for 35 d. Few responses were observed in the LT; however, effects were observed in the MT and HT. Fish mortality occurred in the MT (<35 d) and in the HT (<4 d). Phytoplankton increased in abundance and decreased in diversity (number of taxa) in the HT, with consistent trends being observed in the MT and LT. Zooplankton also showed increased abundance and decreases in diversity in the HT, with consistent trends being observed in the MT. Multivariate analyses for zooplankton and phytoplankton suggested interactions between these communities. Lemna gibba and Myriophyllum spp. showed mortality in the HT; growth of L. gibba was also reduced in the MT. Bacterial abundance did not change in the HT. All responses were observed at concentrations well below the equivalent pharmacologically active concentrations in mammals. Although the present data do not suggest that ibuprofen, fluoxetine, and ciprofloxacin are individually causing adverse effects in surface-water environments, questions remain about additive responses from mixtures.

Dissipation kinetics and mobility of chlortetracycline, tylosin, and monensin in an agricultural soil in Northumberland County, Ontario, Canada

A robust high-throughput method was refined to extract three growth-promoting antibiotics, tylosin (TYL), chlortetracycline (CTC), and monensin (MON), from soil. Analysis was performed by electrospray liquid chromatography tandem mass spectrometry. Soil dissipation rate studies were performed in a farm field soil for antibiotics applied with and without manure. Tylosin, CTC, and MON followed first-order dissipation kinetics with half-lives of 4.5, 24, and 3.3 d, respectively, with the addition of manure and 6.1, 21, and 3.8 d, respectively, without manure. Manure application significantly increased TYL dissipation rate, perhaps because of the introduced microbial flora, but had no significant effect on CTC or MON. Monensin dissipation half-life was found to be much shorter in the field study than in a controlled laboratory study, perhaps because of differences in microbial communities. The antimicrobials were not highly mobile. Chlortetracycline was the only antibiotic detected at 25 to 35 cm depth and only up to 2% of the initial concentration in a sandy loam soil. These antibiotics are therefore expected to degrade primarily in agricultural soils before moving to greater depths or to groundwater in significant concentrations in most agricultural systems.

Disposition of perfluorinated acid isomers in sprague‐dawley rats; Part 1: Single dose

Perfluorinated acids (PFAs) and their precursors (PFA-precursors) exist in the environment as linear and multiple branched isomers. These isomers are hypothesized to have different biological properties, but no isomer-specific data are currently available. The present study is the first in a two-part project examining PFA isomer-specific uptake, tissue distribution, and elimination in a rodent model. Seven male Sprague-Dawley rats were administered a single gavage dose of approximately 500 microg/kg body weight perfluorooctane sulfonate (C(8)F(17)SO(3)(-), PFOS), perfluorooctanoic acid (C(7)F(15)CO(2)H, PFOA), and perfluorononanoic acid (C(8)F(17)CO(2)H, PFNA) and 30 microg/kg body weight perfluorohexane sulfonate (C(6)F(13)SO(3)(-), PFHxS). Over the subsequent 38 d, urine, feces, and tail-vein blood samples were collected intermittently, while larger blood volumes and tissues were collected on days 3 and 38 for isomer analysis by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). For all PFAs, branched isomers generally had lower blood depuration half-lives than the corresponding linear isomer. The most remarkable exception was for the PFOS isomer containing an alpha-perfluoromethyl branch (1m-PFOS), which was threefold more persistent than linear PFOS, possibly due to steric shielding of the hydrophilic sulfonate moiety. For perfluoromonomethyl-branched isomers of PFOS, a structure-property relationship was observed whereby branching toward the sulfonate end of the perfluoroalkyl chain resulted in increased half-lives. For PFHxS, PFOA, and PFOS, preferential elimination of branched isomers occurred primarily via urine, whereas for PFNA preferential elimination of the isopropyl isomer occurred via both urine and feces. Changes in the blood isomer profiles over time and their inverse correlation to isomer elimination patterns in urine, feces, or both provided unequivocal evidence of significant isomer-specific biological handling. Source assignment based on PFA isomer profiles in biota must therefore be conducted with caution, because isomer profiles are unlikely to be conserved in biological samples.

Exploring indirect sources of human exposure to perfluoroalkyl carboxylates (PFCAs): evaluating uptake, elimination, and biotransformation of polyfluoroalkyl phosphate esters (PAPs) in the rat.

Background Perfluorinated carboxylic acids (PFCAs) are ubiquitous in human sera worldwide. Biotransformation of the polyfluoroalkyl phosphate esters (PAPs) is a possible source of PFCA exposure, because PAPs are used in food-contact paper packaging and have been observed in human sera. Objectives We determined pharmacokinetic parameters for the PAP monoesters (monoPAPs) and PAP diesters (diPAPs), as well as biotransformation yields to the PFCAs, using a rat model. Methods The animals were dosed intravenously or by oral gavage with a mixture of 4:2, 6:2, 8:2, and 10:2 monoPAP or diPAP chain lengths. Concentrations of the PAPs and PFCAs, as well as metabolic intermediates and phase II metabolites, were monitored over time in blood, urine, and feces. Results The diPAPs were bioavailable, with bioavailability decreasing as the chain length increased from 4 to 10 perfluorinated carbons. The monoPAPs were not absorbed from the gut; however, we found evidence to suggest phosphate-ester cleavage within the gut contents. We observed biotransformation to the PFCAs for both monoPAP and diPAP congeners. Conclusions Using experimentally derived biotransformation yields, perfluorooctanoic acid (PFOA) sera concentrations were predicted from the biotransformation of 8:2 diPAP at concentrations observed in human serum. Because of the long human serum half-life of PFOA, biotransformation of diPAP even with low-level exposure could over time result in significant exposure to PFOA. Although humans are exposed directly to PFCAs in food and dust, the pharmacokinetic parameters determined here suggest that PAP exposure should be considered a significant indirect source of human PFCA contamination.

Short-term exposures of fish to perfluorooctane sulfonate: acute effects on fatty acyl-coa oxidase activity, oxidative stress, and circulating sex steroids.

This study investigated the effects of exposure to waterborne perfluorooctane sulfonate (PFOS) on oxidative stress and reproductive endpoints in fish. Exposures utilized species commonly used in toxicological testing, including the fathead minnow (Pimephales promelas) and rainbow trout (Oncorhynchus mykiss), as well as relatively insensitive taxa such as creek chub (Semotilus atromaculatus), spottail shiner (Notropis hudsonius), and white sucker (Catostomus commersoni). In all fish species, short-term (14-28 d) exposure to PFOS produced only modest mortality at concentrations consistent with environmental spill scenarios. However, PFOS consistently increased hepatic fatty acyl-CoA oxidase activity and increased oxidative damage, as quantified using the 2-thiobarbituric acid-reactive substances assay. Plasma testosterone, 11-ketotestosterone, and 17beta-estradiol titers were often elevated with PFOS exposure. Vitellogenin, the egg yolk precursor protein, was occasionally altered in the plasma with PFOS exposure, but responses varied with maturity. Oviposition frequency and egg deposition in fathead minnow were not significantly impaired with PFOS exposure, despite a trend toward progressive impairment with increasing exposure concentrations. Although short-term PFOS exposure produced significant impacts on biochemical and reproductive endpoints in fish at concentrations consistent with environmental spills, the impact of long-term exposure to environmentally relevant concentrations of PFOS is unclear.