Toxics

Research

Jump to: Review

17 pages, 978 KiB

Open AccessFeature PaperArticle

Placental Transfer and Composition of Perfluoroalkyl Substances (PFASs): A Korean Birth Panel of Parent-Infant Triads

by Habyeong Kang, Hee-Sun Kim, Yeong Sook Yoon, Jeongsun Lee, Younglim Kho, Jisun Lee, Hye Jin Chang, Yoon Hee Cho and Young Ah Kim

Toxics 2021, 9(7), 168; https://doi.org/10.3390/toxics9070168 - 14 Jul 2021

Cited by 17 | Viewed by 3023

Abstract

Exposure to perfluoroalkyl substances (PFASs) is of public concern due to their persistent exposure and adverse health effects. Placental transfer of PFASs is an important excretion pathway of these chemicals in pregnant women and exposure route in fetuses. We measured PFAS concentrations in [...] Read more.

Exposure to perfluoroalkyl substances (PFASs) is of public concern due to their persistent exposure and adverse health effects. Placental transfer of PFASs is an important excretion pathway of these chemicals in pregnant women and exposure route in fetuses. We measured PFAS concentrations in maternal, paternal, and umbilical cord serum collected from 62 pregnant Korean women and matched biological fathers of the fetuses. Placental transfer rates (cord to maternal serum ratio) of PFASs were also calculated. Demographics and pregnancy-related factors determining the placental transfer rates were identified using linear regression models. Maternal, paternal, and cord serum showed different PFASs compositions. Among the PFASs, perfluorooctane sulfonate (PFOS) showed the highest concentrations in maternal and paternal serum, while perfluorooctanoic acid (PFOA) showed the highest concentration in cord serum. There was a higher proportion of perfluoroalkyl carboxylic acids (PFCAs) with 9–12 carbon chains than those with 13–14 carbon chains in maternal and paternal serum, but this proportion was in the opposite direction in cord serum. PFOA and perfluorohexane sulfonate (PFHxS) had higher placental transfer rates (means of 0.32 and 0.36, respectively) than PFOS (mean of 0.12), which is in line with the results of previous studies. Gestational age and birth weight were positively associated with placental transfer rate of PFOA, PFHxS, and PFOS, while pre-pregnant BMI and weight were inversely associated with PFOS. This study showed that placental transfer of PFASs differs by compounds and is associated with pregnancy-related factors. Further studies on novel PFASs are warranted for Korean pregnant women. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

14 pages, 917 KiB

Open AccessFeature PaperArticle

Immunotoxicity of Per- and Polyfluoroalkyl Substances: Insights into Short-Chain PFAS Exposure

by Tracey Woodlief, Samuel Vance, Qing Hu and Jamie DeWitt

Toxics 2021, 9(5), 100; https://doi.org/10.3390/toxics9050100 - 1 May 2021

Cited by 24 | Viewed by 5804 | Correction

Abstract

Novel per- and polyfluoroalkyl substances (PFAS) were recently identified in drinking water sources throughout North Carolina. These include the perfluoroether acids (PFEAs) perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-2-methoxypropanoic acid (PFMOPrA), and perfluoro-4-methoxybutanioc acid (PFMOBA). Little toxicological data exist for these PFEAs. Therefore, the present study [...] Read more.

Novel per- and polyfluoroalkyl substances (PFAS) were recently identified in drinking water sources throughout North Carolina. These include the perfluoroether acids (PFEAs) perfluoro-2-methoxyacetic acid (PFMOAA), perfluoro-2-methoxypropanoic acid (PFMOPrA), and perfluoro-4-methoxybutanioc acid (PFMOBA). Little toxicological data exist for these PFEAs. Therefore, the present study described signs of toxicity and immunotoxicity following oral exposure. Adult male and female C57BL/6 mice were exposed once/day for 30 days to PFMOAA (0, 0.00025, 0.025, or 2.5 mg/kg), PFMOPrA, or PFMOBA (0, 0.5, 5, or 50 mg/kg). A dose of 7.5 mg/kg of perfluorooctanoic acid (PFOA) was used as a positive control. Terminal body weights, and absolute liver, spleen, or thymus weights did not differ by dose for any compound; exposure to 50 mg/kg of PFMOBA increased relative liver weights in males. Changes in splenic cellularity were observed in males exposed to PFMOPrA and decreased numbers of B and natural killer (NK) cells were observed in males and females exposed to PFMOBA. Exposure did not alter NK cell cytotoxicity or T cell-dependent antibody responses at doses administered. Our results indicate that these “understudied” PFAS have toxicological potential but require additional investigation across endpoints and species, including humans, to understand health effects via drinking water exposure. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

18 pages, 1803 KiB

Open AccessArticle

In-Vitro and In-Silico Assessment of Per- and Polyfluoroalkyl Substances (PFAS) in Aqueous Film-Forming Foam (AFFF) Binding to Human Serum Albumin

by Wenting Li, Yuhong Hu and Heather N. Bischel

Toxics 2021, 9(3), 63; https://doi.org/10.3390/toxics9030063 - 17 Mar 2021

Cited by 24 | Viewed by 5020 | Correction

Abstract

Drinking water contaminated by fluorosurfactant-based aqueous film-forming foams (AFFF) is a source of human exposure to poly- and perfluoroalkyl substances (PFAS). However, assessment of bioaccumulation potentials of diverse PFAS in commercial products such as AFFF have been insufficient and challenging, especially due to [...] Read more.

Drinking water contaminated by fluorosurfactant-based aqueous film-forming foams (AFFF) is a source of human exposure to poly- and perfluoroalkyl substances (PFAS). However, assessment of bioaccumulation potentials of diverse PFAS in commercial products such as AFFF have been insufficient and challenging, especially due to a lack of analytical standards. Here we explore the value of suspect screening, equilibrium dialysis, and molecular-docking simulations to identify potentially bioaccumulative PFAS. We exposed human serum albumin (HSA) protein to dilutions of a legacy AFFF produced by 3M in 1999 using equilibrium dialysis and screened in-vitro protein-binding affinities using high-resolution mass spectrometry (HRMS). Through suspect screening, we identified 32 PFAS and 18 hydrocarbon surfactants in the AFFF that bound to HSA. Quantification of noncovalent association constants for 26 PFAS standards confirmed that many PFAS, including the short-chain perfluoropropane sulfonic acid (log K_a= 4.1 ± 0.2 M⁻¹), exhibit strong binding affinities with HSA. At least five PFAS in AFFF (including three PFAS with less than five perfluorocarbons) remained bound to the precipitated HSA pellet after extensive solvent washing—an indication of high PFAS binding potential. Three PFAS (PFBS, PFOS, and PFOA) were confirmed in the protein pellet with analytical standards and quantified after acid digestion—this sample fraction accounted for 5 to 20% of each compound mass in the sample. We calculated pseudo-bioconcentration factors (BCF_pseudo) for PFAS that suspect screening flagged as noncovalently bound or potentially covalently bound. Most PFAS exhibiting high BCF_pseudo, especially those with seven perfluorocarbons, contained a carboxylic acid or a sulfonic acid. Finally, we used molecular docking to simulate HSA binding affinities for 62 ligands (26 PFAS targets, 18 PFAS qualified in AFFF, and 18 hydrocarbon surfactants qualified in AFFF). We found that molecular docking can effectively separate HSA-binding and -nonbinding compounds in AFFF. In-vitro and in-silico approaches described in this study provide replicable, high-throughput workflows for assessing bioaccumulation potentials of diverse PFAS in commercial products. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

15 pages, 2822 KiB

Open AccessFeature PaperArticle

Perfluoroalkyl Acid Binding with Peroxisome Proliferator-Activated Receptors α, γ, and δ, and Fatty Acid Binding Proteins by Equilibrium Dialysis with a Comparison of Methods

by Manoochehr Khazaee, Emerson Christie, Weixiao Cheng, Mandy Michalsen, Jennifer Field and Carla Ng

Toxics 2021, 9(3), 45; https://doi.org/10.3390/toxics9030045 - 26 Feb 2021

Cited by 32 | Viewed by 4772

Abstract

The biological impacts of per- and polyfluorinated alkyl substances (PFAS) are linked to their protein interactions. Existing research has largely focused on serum albumin and liver fatty acid binding protein, and binding affinities determined with a variety of methods show high variability. Moreover, [...] Read more.

The biological impacts of per- and polyfluorinated alkyl substances (PFAS) are linked to their protein interactions. Existing research has largely focused on serum albumin and liver fatty acid binding protein, and binding affinities determined with a variety of methods show high variability. Moreover, few data exist for short-chain PFAS, though their prevalence in the environment is increasing. We used molecular dynamics (MD) to screen PFAS binding to liver and intestinal fatty acid binding proteins (L- and I-FABPs) and peroxisome proliferator activated nuclear receptors (PPAR-α, -δ and -γ) with six perfluoroalkyl carboxylates (PFCAs) and three perfluoroalkyl sulfonates (PFSAs). Equilibrium dissociation constants, K_Ds, were experimentally determined via equilibrium dialysis (EqD) with liquid chromatography tandem mass spectrometry for protein-PFAS pairs. A comparison was made between K_Ds derived from EqD, both here and in literature, and other in vitro approaches (e.g., fluorescence) from literature. EqD indicated strong binding between PPAR-δ and perfluorobutanoate (0.044 ± 0.013 µM) and perfluorohexane sulfonate (0.035 ± 0.0020 µM), and between PPAR-α and perfluorohexanoate (0.097 ± 0.070 µM). Unlike binding affinities for L-FABP, which increase with chain length, K_Ds for PPARs showed little chain length dependence by either MD simulation or EqD. Compared with other in vitro approaches, EqD-based K_Ds consistently indicated higher affinity across different proteins. This is the first study to report PPARs binding with short-chain PFAS with K_Ds in the sub-micromolar range. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

18 pages, 2690 KiB

Open AccessArticle

Epigenetic Modifications, and Alterations in Cell Cycle and Apoptosis Pathway in A549 Lung Carcinoma Cell Line upon Exposure to Perfluoroalkyl Substances

by Musarrat Jabeen, Muhammad Fayyaz and Joseph Irudayaraj

Toxics 2020, 8(4), 112; https://doi.org/10.3390/toxics8040112 - 23 Nov 2020

Cited by 22 | Viewed by 4079

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a group of human-made compounds with strong C-F bonds, and have been used in various manufacturing industries for decades. PFAS have been reported to deleterious effect on human health, which has led to studies identifying the possible [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are a group of human-made compounds with strong C-F bonds, and have been used in various manufacturing industries for decades. PFAS have been reported to deleterious effect on human health, which has led to studies identifying the possible toxicity and toxicity routes of these compounds. We report that these compounds have the potential to cause epigenetic modifications, and to induce dysregulation in the cell proliferation cycle as well as apoptosis in A549 lung cancer cells when exposed to 10-, 200- and 400 μM concentrations of each compound. Our studies show that exposure to perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) may cause hypomethylation in the epigenome, but changes in the epigenetic makeup are not evident upon exposure to GenX. We establish that exposure to lower doses of these compounds causes the cells’ balance to shift to cell proliferation, whereas exposure to higher concentrations shifts the balance more towards apoptosis. Furthermore, the apoptosis pathway upon exposure to GenX, PFOA, and PFOS has also been identified. Our findings suggest that exposure to any of these compounds may have profound effects in patients with pre-existing lung conditions or could trigger lung cancinogenesis. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

16 pages, 2477 KiB

Open AccessArticle

Effect of Perfluorooctanoic Acid on the Epigenetic and Tight Junction Genes of the Mouse Intestine

by Faizan Rashid, Saeed Ahmad and Joseph Maria Kumar Irudayaraj

Toxics 2020, 8(3), 64; https://doi.org/10.3390/toxics8030064 - 28 Aug 2020

Cited by 24 | Viewed by 4071

Abstract

Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is [...] Read more.

Perfluorooctanoic acid (PFOA) has been implicated in various toxicities including neurotoxicity, genotoxicity, nephrotoxicity, epigenetic toxicity, immunotoxicity, reproductive toxicity, and hepatotoxicity. However, information on the accumulation of PFOA in the intestine and its toxic effects on intestinal epigenetics and tight junction (TJ) genes is sparse. CD1 mice were dosed with PFOA (1, 5, 10, or 20 mg/kg/day) for 10 days, and its accumulation and induced alterations in the expression of epigenetic and tight junction genes in the small intestine and colon were evaluated using LC–MS and qPCR techniques. PFOA reduced the expression levels of DNA methyltransferases (Dnmt1, Dnmt3a, Dnmt3b) primarily in the small intestine whereas, in the colon, a decrease was observed only at high concentrations. Moreover, ten-eleven translocation genes (Tet2 and Tet3) expression was dysregulated in the small intestine, whereas in the colon Tets remained unaffected. The tight junction genes Claudins (Cldn), Occludin (Ocln), and Tight Junction Protein (Tjp) were also heavily altered in the small intestine. TJs responded differently across the gut, in proportion to PFOA dosing. Our study reveals that PFOA triggers DNA methylation changes and alters the expression of genes essential for maintaining the physical barrier of intestine, with more profound effects in the small intestine compared to the colon. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

10 pages, 5002 KiB

Open AccessArticle

Orally Administered 6:2 Chlorinated Polyfluorinated Ether Sulfonate (F-53B) Causes Thyroid Dysfunction in Rats

by So-Hye Hong, Seung Hee Lee, Jun-Young Yang, Jin Hee Lee, Ki Kyung Jung, Ji Hyun Seok, Sung-Hee Kim, Ki Taek Nam, Jayoung Jeong, Jong Kwon Lee and Jae-Ho Oh

Toxics 2020, 8(3), 54; https://doi.org/10.3390/toxics8030054 - 8 Aug 2020

Cited by 15 | Viewed by 3921

Abstract

The compound 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a replacement for perfluorooctanesulfonate (PFOS) in the electroplating industry, has been widely detected in numerous environmental matrices, human sera, and organisms. Due to regulations that limit PFOS use, F-53B use is expected to increase. Therefore, [...] Read more.

The compound 6:2 chlorinated polyfluorinated ether sulfonate (F-53B), a replacement for perfluorooctanesulfonate (PFOS) in the electroplating industry, has been widely detected in numerous environmental matrices, human sera, and organisms. Due to regulations that limit PFOS use, F-53B use is expected to increase. Therefore, in this study, we performed a subchronic oral toxicity study of F-53B in Sprague Dawley (SD) rats. F-53B was administered orally once daily to male and female rats for 28 days at doses of 5, 20, and 100 mg/kg/day. There were no toxicologically significant changes in F-53B-treated rats, except in the thyroid gland. However, F-53B slightly reduced the serum concentrations of thyroid hormones, including triiodothyronine and thyroxine, compared with their concentrations in the vehicle group. F-53B also induced follicular hyperplasia and was associated with increased thyroid hormone biosynthesis-associated protein expression. These results demonstrate that F-53B is a strong regulator of thyroid hormones in SD rats as it disrupts thyroid function. Thus, caution should be exercised in the industrial application of F-53B as an alternative for PFOS. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

Review

Jump to: Research

20 pages, 555 KiB

Open AccessEditor’s ChoiceReview

Per- and Polyfluoroalkyl Substances (PFAS) Neurotoxicity in Sentinel and Non-Traditional Laboratory Model Systems: Potential Utility in Predicting Adverse Outcomes in Human Health

by Rachel Foguth, Maria S. Sepúlveda and Jason Cannon

Toxics 2020, 8(2), 42; https://doi.org/10.3390/toxics8020042 - 15 Jun 2020

Cited by 30 | Viewed by 8516

Abstract

Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals that were widely used in manufacturing and are now present in the environment throughout the world. It is known that various PFAS are quantifiable in human in blood, but potential adverse health outcomes [...] Read more.

Per- and polyfluoroalkyl substances (PFAS) are a class of chemicals that were widely used in manufacturing and are now present in the environment throughout the world. It is known that various PFAS are quantifiable in human in blood, but potential adverse health outcomes remain unclear. Sentinel and non-traditional model species are useful to study potential toxicity of PFAS in order to understand the relationship between environmental and human health. Here, we present a critical review of studies on the neurotoxicity of PFAS in sentinel and non-traditional laboratory model systems, including Caenorhabditis elegans (nematode), Dugesia japonica (planarian), Rana pipiens (frogs), Danio rerio and Oryzias melastigma (fish), and Ursus maritimus (polar bears). PFAS have been implicated in developmental neurotoxicity in non-traditional and traditional model systems as well as sentinel species, including effects on neurotransmitter levels, especially acetylcholine and its metabolism. However, further research on the mechanisms of toxicity needs to be conducted to determine if these chemicals are affecting organisms in a similar manner. Overall, findings tend to be similar among the various species, but bioaccumulation may vary, which needs to be taken into account in future studies by quantifying target organ concentrations of PFAS to better compare different species. Furthermore, data on the majority of PFAS is lacking in neurotoxicity testing, and additional studies are needed to corroborate findings thus far. Full article

(This article belongs to the Special Issue Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS))

► Show Figures

Figure 1

Journal Menu

Journal Browser

Biological Fate and Potential Hazards of Per- and Polyfluorinated Alkyl Substances (PFAS)

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI