Endocrine disruption by PFAS: A major concern associated with legacy and replacement substances

Panieri, Emiliano; Buha-Đorđević, Aleksandra; Saso, Luciano

doi:10.5937/arhfarm71-34197

Cited by 4 publications

(2 citation statements)

References 172 publications

(163 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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%

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.

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

Section: Introductionmentioning

confidence: 99%

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.

View full text Add to dashboard Cite

show abstract

“…Those chemicals which are still on the market are regulated through the Registration, Evaluation, and Authorization of Chemicals (REACH). Nevertheless, POPs are still to be found in both human and animal tissues worldwide [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Aaseth

Javorac

Djordjevic

et al. 2022

Toxics

View full text Add to dashboard Cite

Persistent organic pollutants (POPs) are considered as potential obesogens that may affect adipose tissue development and functioning, thus promoting obesity. However, various POPs may have different mechanisms of action. The objective of the present review is to discuss the key mechanisms linking exposure to POPs to adipose tissue dysfunction and obesity. Laboratory data clearly demonstrate that the mechanisms associated with the interference of exposure to POPs with obesity include: (a) dysregulation of adipogenesis regulators (PPARγ and C/EBPα); (b) affinity and binding to nuclear receptors; (c) epigenetic effects; and/or (d) proinflammatory activity. Although in vivo data are generally corroborative of the in vitro results, studies in living organisms have shown that the impact of POPs on adipogenesis is affected by biological factors such as sex, age, and period of exposure. Epidemiological data demonstrate a significant association between exposure to POPs and obesity and obesity-associated metabolic disturbances (e.g., type 2 diabetes mellitus and metabolic syndrome), although the existing data are considered insufficient. In conclusion, both laboratory and epidemiological data underline the significant role of POPs as environmental obesogens. However, further studies are required to better characterize both the mechanisms and the dose/concentration-response effects of exposure to POPs in the development of obesity and other metabolic diseases.

show abstract

Sublethal Exposure of Per‐ and Polyfluoroalkyl Substances of Varying Chain Length and Polar Functionality Results in Distinct Metabolic Responses in Daphnia magna

Labine

Pereira

Kleywegt

et al. 2022

Enviro Toxic and Chemistry

View full text Add to dashboard Cite

Per‐ and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants used in industrial applications because of their physicochemical properties, which results in their ubiquitous presence across environmental matrices. To date, legacy PFAS have been well studied; however, the concentration of alternative PFAS may exceed the concentration of legacy pollutants, and more information is needed regarding the sublethal toxicity at the molecular level of aquatic model organisms, such as Daphnia magna. Perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) are four widely detected PFAS alternatives of varying chain length and polar functionality that are quantified in aquatic environments. The present study examines the metabolic perturbations of PFAS with varying chemistries to D. magna using targeted mass spectrometry–based metabolomics. Daphnia were acutely exposed to sublethal concentrations of PFBA, PFHxA, PFHxS, and PFNA before the polar metabolite profile was extracted from single organisms. Multivariate analysis demonstrated significant separation between the sublethal concentrations of PFHxA, PFHxS, and PFNA relative to the controls; in sum, longer chain lengths demonstrated greater overall perturbations to the extracted metabolic profiles. Univariate statistics revealed significant perturbations in the concentrations of several amino acids, nucleotides/nucleosides, and neurotransmitters with exposure to PFAS. These metabolic perturbations are consistent with disruptions in energy metabolism (pantothenate and coenzyme A metabolism, histidine metabolism) and protein synthesis (aminoacyl‐transfer RNA biosynthesis and amino acid metabolism), which were identified through biochemical pathway analysis. These results provide evidence that although PFAS chemistry (chain length and polar functional group) invokes unique metabolic responses, there is also an underlying toxic mode of action that is common with select PFAS exposure. Overall, the present study highlights the capabilities of environmental metabolomics to elucidate the molecular‐level perturbations of pollutants within the same chemical class to model aquatic organisms, which can be used to prioritize risk assessment of substituted PFAS alternatives. Environ Toxicol Chem 2023;42:242–256. © 2022 SETAC

show abstract

Endocrine disruption by PFAS: A major concern associated with legacy and replacement substances

Cited by 4 publications

References 172 publications

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

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

The Role of Persistent Organic Pollutants in Obesity: A Review of Laboratory and Epidemiological Studies

Sublethal Exposure of Per‐ and Polyfluoroalkyl Substances of Varying Chain Length and Polar Functionality Results in Distinct Metabolic Responses in Daphnia magna

Contact Info

Product

Resources

About