The authors have designated this AOP as all rights reserved. Re-use in any form requires advanced permission from the authors.

AOP: 538

Title

A descriptive phrase which references both the Molecular Initiating Event and Adverse Outcome.It should take the form “MIE leading to AO”. For example, “Aromatase inhibition leading to reproductive dysfunction” where Aromatase inhibition is the MIE and reproductive dysfunction the AO. In cases where the MIE is unknown or undefined, the earliest known KE in the chain (i.e., furthest upstream) should be used in lieu of the MIE and it should be made clear that the stated event is a KE and not the MIE.  More help

Adverse outcome pathway of PFAS-induced vascular disrupting effects via activating oxidative stress related pathways

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
The vascular toxicology of PFAS
The current version of the Developer's Handbook will be automatically populated into the Handbook Version field when a new AOP page is created.Authors have the option to switch to a newer (but not older) Handbook version any time thereafter. More help
Handbook Version v2.7

Graphical Representation

A graphical representation of the AOP.This graphic should list all KEs in sequence, including the MIE (if known) and AO, and the pair-wise relationships (links or KERs) between those KEs. More help
Click to download graphical representation template Explore AOP in a Third Party Tool

Authors

The names and affiliations of the individual(s)/organisation(s) that created/developed the AOP. More help

Wei yanhong

Point of Contact

The user responsible for managing the AOP entry in the AOP-KB and controlling write access to the page by defining the contributors as described in the next section.   More help
Yanhong Wei   (email point of contact)

Contributors

Users with write access to the AOP page.  Entries in this field are controlled by the Point of Contact. More help
  • Yanhong Wei

Coaches

This field is used to identify coaches who supported the development of the AOP.Each coach selected must be a registered author. More help

OECD Information Table

Provides users with information concerning how actively the AOP page is being developed and whether it is part of the OECD Workplan and has been reviewed and/or endorsed. OECD Project: Assigned upon acceptance onto OECD workplan. This project ID is managed and updated (if needed) by the OECD. OECD Status: For AOPs included on the OECD workplan, ‘OECD status’ tracks the level of review/endorsement of the AOP . This designation is managed and updated by the OECD. Journal-format Article: The OECD is developing co-operation with Scientific Journals for the review and publication of AOPs, via the signature of a Memorandum of Understanding. When the scientific review of an AOP is conducted by these Journals, the journal review panel will review the content of the Wiki. In addition, the Journal may ask the AOP authors to develop a separate manuscript (i.e. Journal Format Article) using a format determined by the Journal for Journal publication. In that case, the journal review panel will be required to review both the Wiki content and the Journal Format Article. The Journal will publish the AOP reviewed through the Journal Format Article. OECD iLibrary published version: OECD iLibrary is the online library of the OECD. The version of the AOP that is published there has been endorsed by the OECD. The purpose of publication on iLibrary is to provide a stable version over time, i.e. the version which has been reviewed and revised based on the outcome of the review. AOPs are viewed as living documents and may continue to evolve on the AOP-Wiki after their OECD endorsement and publication.   More help
OECD Project # OECD Status Reviewer's Reports Journal-format Article OECD iLibrary Published Version
This AOP was last modified on July 09, 2024 06:01

Revision dates for related pages

Page Revision Date/Time
Oxidative Stress November 15, 2024 10:33
The NO synthase pathway activation July 09, 2024 05:56
increased,Vascular endothelial dysfunction September 01, 2021 20:37
Increase, Vascular disrupting effects August 19, 2023 20:12
Ferroptosis related pathways activation July 09, 2024 06:00
Oxidative Stress leads to The NO synthase pathway activation July 09, 2024 06:00
Oxidative Stress leads to Ferroptosis related pathways activation July 09, 2024 06:01
The NO synthase pathway activation leads to increased,Vascular endothelial dysfunction July 09, 2024 06:01
Ferroptosis related pathways activation leads to increased,Vascular endothelial dysfunction July 09, 2024 06:01
increased,Vascular endothelial dysfunction leads to Increase, Vascular disrupting effects July 09, 2024 06:01

Abstract

A concise and informative summation of the AOP under development that can stand-alone from the AOP page. The aim is to capture the highlights of the AOP and its potential scientific and regulatory relevance. More help

Perfluorinated and polyfluoroalkyl compounds are important chemical products, and their types, quantity and population exposure load are increasing year by year, and they are widely used in many fields, such as new fluorine-containing materials, fire protection, electroplating, semiconductors, photovoltaic, aerospace and many other fields. closely related to the development of high-end industry and national security, its potential vascular health hazards and vascular risk has become a major scientific issue of urgent concern all over the world. Traditional and emerging perfluorinated compounds have a wide variety and a large number. The assessment of cardiovascular developmental toxicity and health effects is an important scientific issue of urgent concern in China and the world. In order to effectively ensure the safety of the ecological environment and people's health, relevant regulations have been promulgated at home and abroad, and a number of human biological monitoring projects have been established, but the previous research conclusions on the relationship between traditional perfluorinated compounds and their substitutes and vascular developmental diseases are not consistent, and the harmful outcome path framework of traditional and emerging PFAS vascular interference has not been clarified. The purpose of this study is to clarify the mechanism and health effects of perfluorinated compounds exposure on oxidative stress related pathways, vascular injury and health effects from the point of view of toxicology and epidemiology, so as to lay a solid theoretical foundation for the screening, control and evaluation of perfluorinated and polyfluoroalkyl compounds.

AOP Development Strategy

Context

Used to provide background information for AOP reviewers and users that is considered helpful in understanding the biology underlying the AOP and the motivation for its development.The background should NOT provide an overview of the AOP, its KEs or KERs, which are captured in more detail below. More help

Strategy

Provides a description of the approaches to the identification, screening and quality assessment of the data relevant to identification of the key events and key event relationships included in the AOP or AOP network.This information is important as a basis to support the objective/envisaged application of the AOP by the regulatory community and to facilitate the reuse of its components.  Suggested content includes a rationale for and description of the scope and focus of the data search and identification strategy/ies including the nature of preliminary scoping and/or expert input, the overall literature screening strategy and more focused literature surveys to identify additional information (including e.g., key search terms, databases and time period searched, any tools used). More help

Summary of the AOP

This section is for information that describes the overall AOP.The information described in section 1 is entered on the upper portion of an AOP page within the AOP-Wiki. This is where some background information may be provided, the structure of the AOP is described, and the KEs and KERs are listed. More help

Events:

Molecular Initiating Events (MIE)
An MIE is a specialised KE that represents the beginning (point of interaction between a prototypical stressor and the biological system) of an AOP. More help
Key Events (KE)
A measurable event within a specific biological level of organisation. More help
Adverse Outcomes (AO)
An AO is a specialized KE that represents the end (an adverse outcome of regulatory significance) of an AOP. More help
Type Event ID Title Short name
KE 1392 Oxidative Stress Oxidative Stress
KE 2240 The NO synthase pathway activation The NO synthase pathway activation
KE 1928 increased,Vascular endothelial dysfunction increased,Vascular endothelial dysfunction
KE 2241 Ferroptosis related pathways activation Ferroptosis related pathways activation
AO 2161 Increase, Vascular disrupting effects Increase, Vascular disrupting effects

Relationships Between Two Key Events (Including MIEs and AOs)

This table summarizes all of the KERs of the AOP and is populated in the AOP-Wiki as KERs are added to the AOP.Each table entry acts as a link to the individual KER description page. More help

Network View

This network graphic is automatically generated based on the information provided in the MIE(s), KEs, AO(s), KERs and Weight of Evidence (WoE) summary tables. The width of the edges representing the KERs is determined by its WoE confidence level, with thicker lines representing higher degrees of confidence. This network view also shows which KEs are shared with other AOPs. More help

Prototypical Stressors

A structured data field that can be used to identify one or more “prototypical” stressors that act through this AOP. Prototypical stressors are stressors for which responses at multiple key events have been well documented. More help

Life Stage Applicability

The life stage for which the AOP is known to be applicable. More help

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) can be selected.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available. More help

Sex Applicability

The sex for which the AOP is known to be applicable. More help

Overall Assessment of the AOP

Addressess the relevant biological domain of applicability (i.e., in terms of taxa, sex, life stage, etc.) and Weight of Evidence (WoE) for the overall AOP as a basis to consider appropriate regulatory application (e.g., priority setting, testing strategies or risk assessment). More help

Domain of Applicability

Addressess the relevant biological domain(s) of applicability in terms of sex, life-stage, taxa, and other aspects of biological context. More help

Essentiality of the Key Events

The essentiality of KEs can only be assessed relative to the impact of manipulation of a given KE (e.g., experimentally blocking or exacerbating the event) on the downstream sequence of KEs defined for the AOP. Consequently, evidence supporting essentiality is assembled on the AOP page, rather than on the independent KE pages that are meant to stand-alone as modular units without reference to other KEs in the sequence. The nature of experimental evidence that is relevant to assessing essentiality relates to the impact on downstream KEs and the AO if upstream KEs are prevented or modified. This includes: Direct evidence: directly measured experimental support that blocking or preventing a KE prevents or impacts downstream KEs in the pathway in the expected fashion. Indirect evidence: evidence that modulation or attenuation in the magnitude of impact on a specific KE (increased effect or decreased effect) is associated with corresponding changes (increases or decreases) in the magnitude or frequency of one or more downstream KEs. More help

Evidence Assessment

Addressess the biological plausibility, empirical support, and quantitative understanding from each KER in an AOP. More help

Known Modulating Factors

Modulating factors (MFs) may alter the shape of the response-response function that describes the quantitative relationship between two KES, thus having an impact on the progression of the pathway or the severity of the AO.The evidence supporting the influence of various modulating factors is assembled within the individual KERs. More help
Modulating Factor (MF) Influence or Outcome KER(s) involved
     

Quantitative Understanding

Optional field to provide quantitative weight of evidence descriptors.  More help

Considerations for Potential Applications of the AOP (optional)

Addressess potential applications of an AOP to support regulatory decision-making.This may include, for example, possible utility for test guideline development or refinement, development of integrated testing and assessment approaches, development of (Q)SARs / or chemical profilers to facilitate the grouping of chemicals for subsequent read-across, screening level hazard assessments or even risk assessment. More help

References

List of the literature that was cited for this AOP. More help

[1]        LAING S, WANG G, BRIAZOVA T, et al. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues [J]. American journal of physiology Cell                physiology, 2010, 299(4): C736-49.

[2]        CUI J, WANG P, YAN S, et al. Perfluorooctane Sulfonate Induces Dysfunction of Human Umbilical Vein Endothelial Cells via Ferroptosis Pathway [J]. Toxics, 2022, 10(9).

[3]        STOCKWELL B R, JIANG X, GU W. Emerging Mechanisms and Disease Relevance of Ferroptosis [J]. Trends in cell biology, 2020, 30(6): 478-90.

[4]        GAO M, JIANG X. To eat or not to eat-the metabolic flavor of ferroptosis [J]. Current opinion in cell biology, 2018, 51: 58-64.

[5]        DIXON S J, LEMBERG K M, LAMPRECHT M R, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death [J]. Cell, 2012, 149(5): 1060-72.

[6]        INCALZA M A, D'ORIA R, NATALICCHIO A, et al. Oxidative stress and reactive oxygen species in endothelial dysfunction associated with cardiovascular and metabolic diseases [J]. Vascul Pharmacol, 2018, 100: 1-19.

[7]        DOLL S, PRONETH B, TYURINA Y Y, et al. ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition [J]. Nature chemical biology, 2017, 13(1): 91-8.

[8]        ZHAO Y, ZHAO H, XU H, et al. Perfluorooctane sulfonate exposure induces preeclampsia-like syndromes by damaging trophoblast mitochondria in pregnant mice [J]. Ecotoxicology and environmental safety, 2022, 247: 114256.

[9]        DU Y, CAI Z, ZHOU G, et al. Perfluorooctanoic acid exposure increases both proliferation and apoptosis of human placental trophoblast cells mediated by ER stress-induced ROS or UPR pathways [J]. Ecotoxicology and environmental safety, 2022, 236: 113508.

[10]      BLAKE B E, RICKARD B P, FENTON S E. A High-Throughput Toxicity Screen of 42 Per- and Polyfluoroalkyl Substances (PFAS) and Functional Assessment of Migration and Gene Expression in Human Placental Trophoblast Cells [J]. Frontiers in toxicology, 2022, 4: 881347.

[11]      BONATO M, CORRà F, BELLIO M, et al. Pfas environmental pollution and antioxidant responses: An overview of the impact on human field [J]. International Journal of Environmental Research and Public Health, 2020, 17(21): 1-45.

[12]      SONKAR R, KAY M K, CHOUDHURY M. PFOS Modulates Interactive Epigenetic Regulation in First-Trimester Human Trophoblast Cell Line HTR-8/SV(neo) [J]. Chemical research in toxicology, 2019, 32(10): 2016-27.

[13]      JIANG J, CHEN D Y, LIU Z T, et al. Effect of N-Perfluorooctane on Hypoxia/Reoxygenation Injury in Human Umbilical Vein Endothelial Cells [J]. Acta Cardiologica Sinica, 2016, 32(6): 716-22.

[14]      LIAO Y, WANG J, HUANG Q S, et al. Evaluation of cellular response to perfluorooctane sulfonate in human umbilical vein endothelial cells [J]. Toxicology in vitro : an international journal published in association with BIBRA, 2012, 26(3): 421-8.

[15]     QIAN Y, DUCATMAN A, WARD R, et al. Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability [J]. Journal of toxicology and environmental health Part A, 2010, 73(12): 819-36.

[16]      MARINELLO W P, MOHSENI Z S, CUNNINGHAM S J, et al. Perfluorobutane sulfonate exposure disrupted human placental cytotrophoblast cell proliferation and invasion involving in dysregulating preeclampsia related genes [J]. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2020, 34(11): 14182-99.