Elsevier

Environmental Pollution

Volume 267, December 2020, 115611
Environmental Pollution

Biotransformation and tissue bioaccumulation of 8:2 fluorotelomer alcohol in broiler by oral exposure

https://doi.org/10.1016/j.envpol.2020.115611Get rights and content

Highlights

  • Metabolism, tissue distribution and accumulation of 8:2 FTOH in broiler were studied.

  • The 8:2 fluorotelomer alcohol was swiftly depleted in broiler.

  • The metabolism of 8:2 fluorotelomer alcohol in broiler includesⅠand II reaction.

  • 8:2 FTOH and its metabolites were mainly accumulated in heart, kidneys and liver.

  • PFNA and 7:3 FTCA are potential markers of 8:2 FTOH.

Abstract

In order to examine whether 8:2 FTOH exposure would lead to a contamination risk of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in broiler derived food, the biotransformation, and tissue distribution and accumulation of 8:2 FTOH following oral exposure in male broilers were investigated. The main metabolites of 8:2 FTOH in plasma and six tissues (muscle, liver, kidney, fat, heart, and lungs) identified by LC-Q-TOF were 2-perfluorooctyl ethanoic acid (8:2 FTCA), 8:2 fluorotelomer unsaturated carboxylic acid (8:2 FTUCA), 3-perfluoroheptyl propanoic acid (7:3 FTCA), perfluoropentanoic acid (PFPeA), perfluorooctanoic acid (PFOA), perfluoroheptanoic acid (PFHpA), perfluorohexanoic acid (PFHxA), perfluorononanoic acid (PFNA), 8:2 FTOH glucuronide conjugate, and 8:2 FTOH sulfate conjugate. The tissue distribution and bioaccumulation of 8:2 FTOH and its unconjugated metabolites were determinated by LC-MS/MS. 8:2 FTOH was quickly depleted in plasma and all six tested tissues, while PFOA, PFNA, and 7:3 FTCA showed strong accumulation in blood and all six examined tissues and were eliminated more slowly than the other metabolites. The tissues with the highest accumulation levels for 8:2 FTOH and its metabolites were heart, kidneys and liver, and the tissue with the lowest accumulation levels was muscle. The elimination half-lifes of PFNA in kidney and 7:3 FTCA in lung were longer compared to those of other metabolites in all six determined tissues. Thus, PFNA and 7:3 FTCA can be selected as potential biomonitoring markers after 8:2 FTOH exposure. This study has improved our understanding of 8:2 FTOH biotransformation and tissue bioaccumulation in broilers, which will help us monitor human exposure risk via food derived from broilers polluted by 8:2 FTOH.

Introduction

Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are widely used for producing commercial and industrial products, including textile dyes, coatings, leathers, cookware, food, packaging, synthetic detergents, pesticides and other industry products (Kissa, 2001). PFASs are usually produced by electrochemical fluorination (ECF) and telomerization (Buck et al., 2011, Collins et al., 2014; D’eon and Mabury, 2011; Hekster et al., 2003). ECF-associated chemical perfluorooctane sulfonate (PFOS) and perfluorooctane sulfonyl fluoride (POSF) have been placed into the Annex B of the Stockholm Convention (SC) on Persistent Organic Pollutants (POPs) in 2009. The ECF production has also been phased out in the United States. Thus, the production of fluorotelomer alcohols (FTOHs) by telomerization has increased significantly (Prevedouros et al., 2006). FTOHs (F(CF2)XCH2CH2OH, x = 4, 6, 8, 10) are the main telomerization products, with annual output of up to 5.0–6.5 × 106 kg during the period of 2000–2002. An estimated 20 million pounds of FTOHs were produced in 2006 (Huang et al., 2019). Among all the FTOHs, 8:2 FTOH has the highest yield and is widely distributed in various environmental media, animals, and humans via atmospheric circulation and long-distance migration due to its volatility and water flow (Bhhatarai and Gramatica, 2012). The geometric mean of 8:2 FTOH concentration in air in Boston was reportedly 9920 pg/m3 (Fraser et al., 2012). In addition, 8:2 FTOH, as an intermediate product of some FTOH-precursors (e.g., 8:2 fluorotelomer acrylate, 8:2 fluorotelomer stearate monoester, 8:2 fluorotelomer citrate trimester, polyfluoroalkyl phosphates, and fluorotelomer ethoxylates), might lead to the indirect exposure of 8:2 FTOH to the environment and animals (Butt et al., 2014). Even worse, 8:2 FTOH can be metabolized into various perfluocarboxylic acids (PFCAs) via biotransformation and abiotic transformation (Butt et al., 2014; Xie et al., 2020; Zhang et al., 2013b). Therefore, it is an important source of ubiquitous PFCAs.

Exposure to 8:2 FTOH can induce various toxicity on living organisms, such as nephrotoxicity, hepatoxicity, endocrine-disrupting toxicity and gonad toxicity (Ladics et al., 2008; Wang et al., 2019). Its toxicity is related to the 8:2 FTOH and some degradation products. Some degradation products have even stronger toxicities than 8:2 FTOH itself (Phillips et al., 2007). For example, 8:2 FTUCA (an intermediate metabolite) and PFNA (a final metabolite) showed hepatotoxicity in vitro, while 8:2 FTOH showed no hepatotoxicity (Martin et al., 2009). The final degradation product of PFOA can generate reactive oxygen species (ROS), while 8:2 FTOH did not induce ROS production even at a very high concentration (Reistad et al., 2013). The intermediate metabolites of unsaturated aldehydes (FTUALs) can combine with active substances and proteins in organisms, decreasing the level of glutathione and protein carbonylation and increasing lipid peroxidation, hepatomegaly and necrosis, thereby affecting biological functions and producing a series of toxic effects (Fasano et al., 2006, 2009; Rand and Mabury, 2014). The intermediate metabolites (FTUAL and 7-2 sFTOH) of 8:2 FTOH can bind with proteins and cause toxicity, and the final metabolite, PFOA, is recognized as peroxisome proliferator (Rand and Mabury, 2014). Because of the stronger toxicity of some metabolites, investigations of their metabolism are necessary.

Some studies have shown that 8:2 FTOH can be easily and finally metabolized into 8:2 FTOH conjugates and various PFCAs in microbial systems, rats, mice, fish, earthworm, and soybean (Martin et al., 2005; Fasano et al., 2006; Zhang et al., 2016; Brandsma et al., 2011; Butt et al., 2010). The 8:2 FTOH is assumed to be metabolized by phase Ⅰ and Ⅱ metabolism. 8:2 FTOH can ultimately metabolize into PFCAs, such as perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), PFOA, and PFNA. Currently, the metabolites of FTOHs are well characterized but they are different under different conditions (certain species, microbial systems, etc).

Some of the intermediate and final metabolites can bind to various biomolecules and thereby accumulate in the animal body (Rand and Mabury, 2014). Some metabolites also display discrepant accumulation performances in different tissues of various organisms (Perez et al., 2013). After exposure of Sprague-Dawley (SD) rats to 8:2 FTOH for 45 d, PFOA was detected in the plasma, urine and liver of both males and females and in the kidneys of males, while 8:2 uFTOH-SCysNAcetyl and 7:2 sFTOH were only observed in the urine of females (Fasano et al., 2009). Our previous work showed that in pigs after oral dosing, the elimination half-life (T1/2) values were the highest in the heart for PFHpA and in kidney tissue for 7:3 FTCA and PFOA (Xie et al., 2020). It was reported that the T1/2 values of PFOA, PFHpA and PFHxA were 236, 74 and 4.1 d in blood of fattening pigs, respectively (Numata et al., 2014), whereas the T1/2 values of perfluoropentanoic acid (PFPeA), PFHxA, PFHpA, PFNA and PFOA in microminipig plasma were 1.6, 2.7, 34.7, 49.5, and 63 d, respectively (Guruge et al., 2016). Based on the reported results, the tissue distribution and elimination of 8:2 FTOH and its metabolites show obvious species differences.

The persistent and bioaccumulative 8:2 FTOH and its degradation products might be concentrated in animal food and biomagnified through the food chain (Wang et al., 2019; Prevedouros et al., 2006). Some reports have shown that several PFASs can accumulate in upper trophic level organisms via tropic transfer and biomagnification from lower trophic-level organism bioaccumulation (Van de Vijver et al., 2003; ). Bioaccumulation of 8:2 FTOH and its metabolites in animal tissues may have adverse effects on human, as increasing concentrations accumulate up the food chain. Some reports have detected parent 8:2 FTOH and its metabolites in food and package materials (Gewurtz et al., 2016; Jogsten et al., 2009). Diet intake is considered as one of the main exposure routes of humans to PFASs (Jogsten et al., 2009), which is mostly through fish, shellfish and meat consumption (Ericson et al., 2008; Jian et al., 2017; Vestergren et al., 2012). The mean estimated daily intake (EDI) of perfluorochemicals is 1.0–4.0 ng/kg body weight (bw)/d for German (Fromme et al., 2007), Spanish (Ericson et al., 2008; Vestergren et al., 2012), Canadian (Ostertag et al., 2009) and Japanese (Kärrman et al., 2009) consumers. Various PFCAs were detected in chicken meat collected from Siena (Italy), China, Netherlands, Oslo (Norway), and Catalonia (Spain) (Jian et al., 2017). It is estimated by Wang et al. (2015) that terrestrial food (meat) has contributed 93.2% of PFOA to human exposure in China. The concentration of PFOA in chicken, pork, beef, and, goat meat was 12,500, 6170, 4260, and 1560 pg/g, respectively (Zhang et al., 2010).

Overall, exposure to 8:2 FTOH allows the body to simultaneously obtain a variety of structurally similar PFASs due to its metabolism. It is even more worrisome that 8:2 FTOH shows species differences in metabolism and accumulation that may pose a greater threat to the safety of animal-derived foods for humans. To effectively assess the potential exposure risk of humans via animal-derived foods polluted by 8:2 FTOH, the metabolism, distribution and accumulation in food-producing animals should be studied to identify the biomonitoring markers and target tissues of different food-producing animals. Therefore, the metabolism and tissue bioaccumulation of 8:2 FTOH in male broilers were investigated in this work in order to see which metabolites are formed in broilers and the accumulation discrepancy of different metabolites in different tissues of broilers.

Section snippets

Materials

Methanol and acetonitrile with chromatographic purity were bought from Merck Chemicals Co. (Darmstadt, Germany). Standards of the eight main metabolites were obtained from Wellington Laboratories, Inc. (Guelph, Ontario, Canada). The 8:2 FTOH standard was bought from J & K Scientific Ltd. (Lommel, Germany). Sulphatase (≤7500 units/mL) and β-Glucuronidase (≥85,000 units/mL) were bought from Sigma-Aldrich (St. Louis, USA). All other solvents with unspecified emphasis were analytical pure.

Animals

8:2 FTOH metabolites identification

The metabolite confirmation was based on full scanning and ion fragment scanning by LC/MS-Q-TOF. It was reported that the highest concentration of most compounds in rat excreta and plasma is found in the first few hours (Fasano et al., 2006). Therefore, the samples collected at 6 h after 8:2 FTOH ingestion were used to identify the metabolites. To verify the metabolite confirmation results, some obtained metabolite standards were analyzed by LC/MS-Q-TOF and compared with the confirmation

Conclusions

To effectively assess the potential exposure risk of humans to 8:2 FTOH and its metabolites via broiler-derived food, the biotransformation, tissue distribution and tissue bioaccumulation of 8:2 FTOH in male broilers were systematically investigated to confirm the monitoring markers and tissues. The 8:2 FTOH was rapidly metabolized and removed in plasma and tissues, while some of its main metabolites, such as PFOA, PFNA and 7:3 FTCA, showed considerable accumulation in all the tested broiler

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

This work was supported by Natural Science Foundation of China (NSFC, 31572570) and Risk Assessment of unknown and known hazard factors of livestock and poultry products (GJFP2017008).

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