This AOP is licensed under a Creative Commons Attribution 4.0 International License.

Aop: 303

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

Frustrated phagocytosis-induced lung cancer

Short name

A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help

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

Carole Seidel

Sarah Valentino

Laurent Gaté

Institut National de Recherche et de Sécurité, Rue du Morvan, CS 60027, F-54519 Vandœuvre, Cedex, France.

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

Arthur Author (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

Carole Seidel
Sarah Valentino
Laurent GATE
Arthur Author

Status

Provides users with information concerning how actively the AOP page is being developed, what type of use or input the authors feel comfortable with given the current level of development, and whether it is part of the OECD AOP Development Workplan and has been reviewed and/or endorsed. OECD Status - Tracks the level of review/endorsement the AOP has been subjected to. OECD Project Number - Project number is designated and updated by the OECD. SAAOP Status - Status managed and updated by SAAOP curators. More help

Author status	OECD status	OECD project	SAAOP status
Under development: Not open for comment. Do not cite	Under Development	1.86	Included in OECD Work Plan

This AOP was last modified on July 16, 2022 18:37

Revision dates for related pages

Page	Revision Date/Time
Frustrated phagoytosis	August 13, 2019 04:48
Release, Cytokine	September 16, 2017 10:14
Increased, recruitment of inflammatory cells	January 25, 2022 15:52
Increased, Reactive oxygen species	November 27, 2017 13:15
Increased, DNA damage and mutation	August 13, 2019 05:41
Increase, Cell Proliferation	June 23, 2021 12:28
Lung cancer	August 13, 2019 05:34
Frustrated phagoytosis leads to Release, Cytokine	August 13, 2019 05:25
Release, Cytokine leads to Recruitment of inflammatory cells	July 03, 2019 11:52
Recruitment of inflammatory cells leads to Increased, Reactive oxygen species	July 03, 2019 11:53
Increased, Reactive oxygen species leads to Increased, DNA damage and mutation	July 03, 2019 11:53
Increased, DNA damage and mutation leads to Increase, Cell Proliferation	July 03, 2019 11:53
Increase, Cell Proliferation leads to Lung cancer	July 03, 2019 11:53
High aspect ratio material	August 13, 2019 04:38

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

Inhalation of materials, including fibres and particles, represents the main route of occupational exposure. The main issue is the biopersistance of these materials in lungs that could lead to chronic pulmonary pathologies such as fibrosis and cancer. Lung tumour is one of the most prevalent cancer in the world and, in general, is often detected at a late stage.

The knowledge related to the induction of lung disease following asbestos exposure led to study the toxicity of high aspect ratio materials (HARMs) in general. It is now well documented that exposure to HARMs could lead to pulmonary inflammation and ROS overproduction. Some studies suggest that lung biopersistence of HARMs is associated with frustrated phagocytosis and material length. The identified gaps regarding the induction of lung cancer following the exposure to HARMs is mainly on the interaction with cells, and no study demonstrated all the key events presented here in the same samples.

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

MIE

1668

Frustrated phagoytosis

KE	87	Release, Cytokine	Release, Cytokine
KE	1497	Increased, recruitment of inflammatory cells	Recruitment of inflammatory cells
KE	1115	Increased, Reactive oxygen species	Increased, Reactive oxygen species
KE	1669	Increased, DNA damage and mutation	Increased, DNA damage and mutation
KE	870	Increase, Cell Proliferation	Increase, Cell Proliferation

1670

Lung cancer

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

Title	Adjacency	Evidence	Quantitative Understanding

Frustrated phagoytosis leads to Release, Cytokine	adjacent
Release, Cytokine leads to Recruitment of inflammatory cells	adjacent
Recruitment of inflammatory cells leads to Increased, Reactive oxygen species	adjacent
Increased, Reactive oxygen species leads to Increased, DNA damage and mutation	adjacent
Increased, DNA damage and mutation leads to Increase, Cell Proliferation	adjacent
Increase, Cell Proliferation leads to Lung cancer	adjacent

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

Name
High aspect ratio material

Life Stage Applicability

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

Life stage	Evidence
Adult

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

Term	Scientific Term	Evidence	Link
mammals	mammals		NCBI

Sex Applicability

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

Sex	Evidence
Unspecific

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

This AOP is applicable to adult (at least to mature lung tissue), to many vertebrate taxons, and to both genders.

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

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