In Vitro characterization of the endocrine disrupting effects of per- and poly-fluoroalkyl substances (PFASs) on the human androgen receptor

Tachachartvanich, Phum; Ramaprasad, Azhagiya Singam Ettayapuram; Durkin, Kathleen A.; Furlow, J. David; Smith, Martyn T.; Merrill, Michele A. La

doi:10.1016/j.jhazmat.2022.128243

Cited by 18 publications

(9 citation statements)

References 70 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lungs/bronchi Promotion of asthma in youth [393] 4. Endocrinic system Thyroid [217,[394][395][396]; steroid(cortisone) [397][398][399] and sex hormones [398,400,401] 5. Metabolism (a) Glucose [402]; type 2-diabetes [403][404][405][406]; gestational diabetes [213] (b) Fat [387,[407][408][409] (c) Bile acid [387] (d) Total and non-HDL cholesterol [410][411][412] 6.…”

Section: Affected Organ/function Consequencesmentioning

confidence: 99%

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

Brunn

Arnold²,

Körner

et al. 2023

Environ Sci Eur

View full text Add to dashboard Cite

Background Per- and polyfluorinated alkyl substances (PFAS) have received increasing scientific and political attention in recent years. Several thousand commercially produced compounds are used in numerous products and technical processes. Due to their extreme persistence in the environment, humans and all other life forms are, therefore, increasingly exposed to these substances. In the following review, PFAS will be examined comprehensively. Results The best studied PFAS are carboxylic and sulfonic acids with chain lengths of C4 to C14, particularly perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). These substances are harmful to aquatic fauna, insects, and amphibians at concentrations of a few µg/L or less, accumulate in organisms, and biomagnify in food webs. Humans, as the final link in numerous food chains, are subjected to PFAS uptake primarily through food and drinking water. Several PFAS have multiple toxic effects, particularly affecting liver, kidney, thyroid, and the immune system. The latter effect is the basis for the establishment of a tolerable weekly dose of only 4.4 ng/kg body weight for the sum of the four representatives PFOA, PFOS, perfluorononanoic acid (PFNA) and perfluorohexane sulfonic acid (PFHxS) by the European Food Safety Authority (EFSA) in 2020. Exposure estimates and human biomonitoring show that this value is frequently reached, and in many cases exceeded. PFAS are a major challenge for analysis, especially of products and waste: single-substance analyses capture only a fragment of the large, diverse family of PFAS. As a consequence, sum parameters have gained increasing importance. The high mobility of per and polyfluorinated carboxylic and sulfonic acids makes soil and groundwater pollution at contaminated sites a problem. In general, short-chain PFAS are more mobile than long-chain ones. Processes for soil and groundwater purification and drinking water treatment are often ineffective and expensive. Recycling of PFAS-containing products such as paper and food packaging leads to carryover of the contaminants. Incineration requires high temperatures to completely destroy PFAS. After PFOA, PFOS and a few other perfluorinated carboxylic and sulfonic acids were regulated internationally, many manufacturers and users switched to other PFAS: short-chain representatives, per- and polyfluorinated oxo carboxylic acids, telomeric alcohols and acids. Analytical studies show an increase in environmental concentrations of these chemicals. Ultra-short PFAS (chain length C1–C3) have not been well studied. Among others, trifluoroacetic acid (TFA) is present globally in rapidly increasing concentrations. Conclusions The substitution of individual PFAS recognized as hazardous by other possibly equally hazardous PFAS with virtually unknown chronic toxicity can, therefore, not be a solution. The only answer is a switch to fluorine-free alternatives for all applications in which PFAS are not essential.

show abstract

Section: Affected Organ/function Consequencesmentioning

confidence: 99%

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

Brunn

Arnold²,

Körner

et al. 2023

Environ Sci Eur

View full text Add to dashboard Cite

show abstract

“…Previous studies have also highlighted the potential risks PFASs pose to human health, linking them to developmental toxicity, , immunotoxicity, , hepatotoxicity, and tumorigenesis . Studies also associate PFASs with lower bone mineral density and identify them as potential endocrine-disrupting chemicals. ,,− Interference with the activity of native hormones may therefore play an important role in the adverse effects of PFASs.…”

Section: Introductionmentioning

confidence: 99%

“…Kwon et al developed innovative semisupervised machine-learning models to predict the bioactivities of PFASs, offering an efficient and cost-effective alternative to traditional bioactivity assessments and providing insights into the bioactive properties of these widely used substances . In our previous study, we utilized machine learning and molecular modeling to prioritize PFAS chemicals for activity against androgen receptor (AR) and experimentally verified some of the PFASs as competitive antagonists of AR. , …”

Section: Introductionmentioning

confidence: 99%

“…42 In our previous study, we utilized machine learning and molecular modeling to prioritize PFAS chemicals for activity against androgen receptor (AR) and experimentally verified some of the PFASs as competitive antagonists of AR. 27,43 In this study, we take advantage of in silico molecular screening and machine learning to identify PFASs that may strongly interact with several key NRs, including AR, ERA, estrogen receptor−beta (ERB), glucocorticoid receptor (GR), progesterone receptor (PR), PPARA, peroxisome proliferatoractivated receptor delta (PPARD), peroxisome proliferatoractivated receptor gamma (PPARG), mineralocorticoid receptor (MR), and retinoid X receptor alpha (RXRA). Our findings aim to illuminate the potential risks of unstudied PFASs and guide subsequent research and regulatory action.…”

Section: ■ Introductionmentioning

confidence: 99%

“…) ( 3 β ) -25,26,26,26,27,27,27-heptafluoro-cholest-5-en-3-ol (DTXSID80897495), (3) 3-(6,6,7,7,8,8,9,9,9-nonafluorononyl)-4′-octyl-2,2′-bithiophene (DTXSID80844585), (4) 3-(12,12,13,13,14,14,15,15,15-nonafluoropentadecyl)benzene-1,2-diol (DTXSID60895974), and (5) 4′-(heptadecafluorooctyl)-3-octyl-2,2′-bithiophene (DTXSID20827670). These PFASs are predicted to be strong binders with antagonist activity.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Prediction of the Interactions of a Large Number of Per- and Poly-Fluoroalkyl Substances with Ten Nuclear Receptors

Azhagiya Singam,

Durkin,

La Merrill

et al. 2024

Environ. Sci. Technol.

Self Cite

View full text Add to dashboard Cite

Per-and poly-fluoroalkyl substances (PFASs) are persistent, toxic chemicals that pose significant hazards to human health and the environment. Screening large numbers of chemicals for their ability to act as endocrine disruptors by modulating the activity of nuclear receptors (NRs) is challenging because of the time and cost of in vitro and in vivo experiments. For this reason, we need computational approaches to screen these chemicals and quickly prioritize them for further testing. Here, we utilized molecular modeling and machine-learning predictions to identify potential interactions between 4545 PFASs with ten different NRs. The results show that some PFASs can bind strongly to several receptors. Further, PFASs that bind to different receptors can have very different structures spread throughout the chemical space. Biological validation of these in silico findings should be a high priority.

show abstract

Antenatal Exposure to Plastic Pollutants: Study of the Bisphenols and Perfluoroalkyls Effects on Human Stem Cell Models

et al. 2023

View full text Add to dashboard Cite

Endocrine disruptors (EDs), such as Bisphenols (BPs) and Perfluoroalkyls (PFs), are a class of plastic pollutants widely used in industrial applications. Human exposure to these molecules usually occurs through ingestion of contaminated food and water. Once entered the human body they can interfere with endogenous hormone signaling, leading to a wide spectrum of diseases. It has been reported that BPs and PFs can cross the placental barrier accumulating in the fetal serum, but the detrimental consequences for human development remain to be clarified. Here we analyze the effects of different doses of bisphenol A and S (BPA, BPS) perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) on proliferation and mitochondrial health on different types of stem cells: through an integrated approach that combines data from pluripotent stem cells (hiPSCs) with that from the “environment” in which the embryo develops (fetal annexes-derived perinatal stem cells) we verified the potential developmental toxicity of the in utero EDs exposure. Data obtained showed that overall, BPs, and PFs tended to increase the proliferation rate of perinatal stem cells; a similar response was observed in hiPSCs exposed to very low doses of BPs and PFs, while at higher concentrations these chemicals were toxic; in addition, both the BPs and the PFs exerted a mitotoxic effects hiPSCs at all the concentration studied. All these data suggest that antenatal exposure to BPs and PFs, also at very low concentrations, may modify the biological characteristics of stem cells present in both the developing fetus and the fetal annexes, thus perturbing normal human development.

show abstract

In Vitro characterization of the endocrine disrupting effects of per- and poly-fluoroalkyl substances (PFASs) on the human androgen receptor

Cited by 18 publications

References 70 publications

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

PFAS: forever chemicals—persistent, bioaccumulative and mobile. Reviewing the status and the need for their phase out and remediation of contaminated sites

Prediction of the Interactions of a Large Number of Per- and Poly-Fluoroalkyl Substances with Ten Nuclear Receptors

Antenatal Exposure to Plastic Pollutants: Study of the Bisphenols and Perfluoroalkyls Effects on Human Stem Cell Models

Contact Info

Product

Resources

About