Cytotoxicity of novel fluorinated alternatives to long-chain perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty acid binding protein

Sheng, Nan; Cui, Ruina; Wang, Jinghua; Guo, Yong; Wang, Jianshe; Dai, Jiayin

doi:10.1007/s00204-017-2055-1

Cited by 188 publications

(146 citation statements)

References 58 publications

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“…Distribution coefficients to the biological matrices for PFAAs and alternatives originated from the present study or were reported previously and are displayed in Table 1 (Allendorf et al 2019; Ebert et al 2020). The binding affinities to liver FABP were reported elsewhere (Weaver et al 2010; Woodcroft et al 2010; Zhang et al 2013; Sheng et al 2018) and converted to distribution coefficients (Supplemental Data, SI‐1.9). Our distribution calculations assume that distribution coefficients to biological matrices resulting from in vitro experiments can be directly transferred to the in vivo situation and that all components of the organism are at equilibrium with each other.…”

Section: Methodsmentioning

confidence: 99%

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Estimating the Equilibrium Distribution of Perfluoroalkyl Acids and 4 of Their Alternatives in Mammals

Allendorf

Goss

Ulrich

2021

Enviro Toxic and Chemistry

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Perfluoroalkyl acids (PFAAs) mostly exist as ionic compounds that are of major concern because of their accumulative behavior. The discussion about their risk is ongoing considering the increasing production of structurally similar alternatives. We conducted model calculations based on equilibrium distribution coefficients that allow studying the distribution of PFAAs and their alternatives in various mammalian organs through comparison to empirical measurements in humans and rats. The calculations rely on experimentally determined distribution coefficients of a series of PFAAs and 4 of their alternatives to physiological matrices such as structural proteins, storage lipids, membrane lipids, albumin, and fatty acid binding protein (FABP). The relative sorption capacities in each organ were calculated from the combination of distribution coefficients and physiological data. The calculated distribution of PFAAs and alternatives within the organs showed that albumin and membrane lipids and, to a lesser extent, structural proteins have the highest relative sorption capacities for the compounds. Sorption to FABP is only relevant in the distribution of short‐chain PFAAs. Storage lipids play a minor role in the distribution of all studied compounds. Our calculated distribution of PFAAs was evaluated by comparison to reported PFAA concentrations in various organs. Environ Toxicol Chem 2021;40:910–920. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

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Section: Methodsmentioning

confidence: 99%

“…compounds, including PFOA and PFNA (Han et al 2003;van der Vusse 2009;MacManus-Spencer et al 2010;Woodcroft et al 2010;Endo et al 2012;Zhang et al 2013;Sheng et al 2016;Sheng et al 2018).…”

Section: Accepted Articlementioning

confidence: 99%

Estimating the Equilibrium Distribution of Perfluoroalkyl Acids and 4 of Their Alternatives in Mammals

Allendorf

Goss

Ulrich

2021

Enviro Toxic and Chemistry

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“…This is because GenX activates the Peroxisome-proliferator-activated receptor alpha (PPARa) pathway in mouse liver cell lines and causes cell injury (29). In animal models, GenX was also shown to be hepatotoxic and cancerogenic (28,(30)(31)(32). GenX is also highly mobile in the environment being detected faraway from its source.…”

Section: Short-chain and Emerging Replacement Pfasmentioning

confidence: 99%

Thyroid Disrupting Effects of Old and New Generation PFAS

et al. 2021

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Per- and polyfluoroalkyl substances (PFAS) represent a group of synthetic compounds widely used in industry plants due to their low grade of degradation, surfactant properties, thermic and flame resistance. These characteristics are useful for the industrial production, however they are also potentially dangerous for human health and for the environment. PFAS are persistent pollutants accumulating in waters and soil and recoverable in foods due to their release by food packaging. Humans are daily exposed to PFAS because these compounds are ubiquitous and, when assimilated, they are difficult to be eliminated, persisting for years both in humans and animals. Due to their persistence and potential danger to health, some old generation PFAS have been replaced by newly synthesized PFAS with the aim to use alternative compounds presumably safer for humans and the environment. Yet, the environmental pollution with PFAS remains a matter of concern worldwide and led to large-scale epidemiological studies both on plants’ workers and on exposed people in the general population. In this context, strong concern emerged concerning the potential adverse effects of PFAS on the thyroid gland. Thyroid hormones play a critical role in the regulation of metabolism, and thyroid function is related to cardiovascular disease, fertility, and fetal neurodevelopment. In vitro, ex vivo data, and epidemiological studies suggested that PFASs may disrupt the thyroid hormone system in humans, with possible negative repercussions on the outcome of pregnancy and fetal-child development. However, data on the thyroid disrupting effect of PFAS remain controversial, as well as their impact on human health in different ages of life. Aim of the present paper is to review recent data on the effects of old and new generation PFAS on thyroid homeostasis. To this purpose we collected information from in vitro studies, animal models, and in vivo data on exposed workers, general population, and pregnant women.

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“…Previous in vitro studies investigated the toxic effects of several PFAS in different types of cultured cells including thyroid cells [3,[17][18][19][20][21]. However, no information is still available regarding the in vitro effects of C6O4 on thyroid cells.…”

Section: Introductionmentioning

confidence: 99%

The new generation PFAS C6O4 does not produce adverse effects on thyroid cells in vitro

Coperchini

Croce

Pignatti

et al. 2020

J Endocrinol Invest

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Purpose Per- and poly-fluoroalkyl-substances (PFASs) are synthetic compounds that raised concern due to their potential adverse effects on human health. Long-chain PFAS were banned by government rules in many states, and thus, new emerging PFAS were recently introduced as substitutes. Among these, Perfluoro{acetic acid, 2-[(5-methoxy-1,3-dioxolan-4-yl)oxy]}, ammonium salt (C6O4) was recently introduced to produce a range of food contact articles and literature data about this compound are scanty. The aim of this study was to evaluate the in vitro effects of exposure to C6O4, compared with PFOA and PFOS on thyroid cells. Methods FRTL5 rat-thyroid cell lines and normal human thyroid cells (NHT) were incubated with increasing concentrations of C6O4 for 24, 48, 72, and 144 h to assess cell viability by WST-1. Cell viability was confirmed by AnnexinV/PI staining. Long-chain PFAS (PFOA and PFOS) were used at same concentrations as positive controls. The proliferation of cells exposed to C6O4, PFOA, and PFOS was measured by staining with crystal violet and evaluation of optical density after incubation with SDS. Changes in ROS production by FRTL5 and NHT after exposure to C6O4 at short (10, 20, and 30 min) and long-time points (24 h) were evaluated by cytofluorimetry. Results C6O4 exposure did not modify FRTL5 and NHT cell viability at any concentration and/or time points with no induction of necrosis/apoptosis. At difference, PFOS exposure reduced cell viability of FRTL5 while and NHT, while PFOA only in FRTL5. FRTL5 and NHT cell proliferation was reduced by incubation with by PFOA and PFOS, but not with C6O4. ROS production by NHT and FRTL5 cells was not modified after C6O4 exposure, at any time/concentration tested. Conclusions The present in vitro study constitutes the first evaluation of the potential adverse effects of the new emerging PFAS C6O4 in cultured rat and human thyroid cells, suggesting its safety for thyroid cells in vitro.

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Cytotoxicity of novel fluorinated alternatives to long-chain perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty acid binding protein

Cited by 188 publications

References 58 publications

Estimating the Equilibrium Distribution of Perfluoroalkyl Acids and 4 of Their Alternatives in Mammals

Estimating the Equilibrium Distribution of Perfluoroalkyl Acids and 4 of Their Alternatives in Mammals

Thyroid Disrupting Effects of Old and New Generation PFAS

The new generation PFAS C6O4 does not produce adverse effects on thyroid cells in vitro

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