Aop: 187

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

Anticoagulant rodenticide inhibition of vitamin K epoxide reductase resulting coagulopathy and hemorrhage

Short name
A name that succinctly summarises the information from the title. This name should not exceed 90 characters. More help
VKOR inhibition resulting in coagulopathy

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

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
Brendan Ferreri-Hanberry   (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
  • Barnett Rattner
  • Brendan Ferreri-Hanberry

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
Not under active development Under Development 1.31 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
Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis December 03, 2016 16:37
Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) September 16, 2017 10:17
Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) December 03, 2016 16:37
Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal December 03, 2016 16:37
Hemostasis, Depletion from blood of fully functional carboxylated clotting factors December 03, 2016 16:37
Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone December 03, 2016 16:37
Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction December 03, 2016 16:37
Impaired recruitment , Population trajectory December 03, 2016 16:37
Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP September 16, 2017 10:17
Osteoporosis and vascular calcification, Bone deterioration December 03, 2016 16:37
Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin December 03, 2016 16:37
Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carbo leads to Hemostasis, Depletion from blood of fully functional carboxylated clotting factors December 03, 2016 16:38
Hemostasis, Depletion from blood of fully functional carboxylated clotting factors leads to Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failur December 03, 2016 16:38
Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle leads to Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carbo December 03, 2016 16:38
Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failur leads to Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) December 03, 2016 16:38
Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) leads to Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tis December 03, 2016 16:38
Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tis leads to Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction December 03, 2016 16:38
Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction leads to Impaired recruitment , Population trajectory December 03, 2016 16:38
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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

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 1134 Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle vitamin K epoxide to vitamin K to form vitamin K hydroquinone Irreversible inhibition of hepatic VKOR by binding of AR at tyrosine 139, Failure to cycle
MIE 1138 Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP Uncoupling of oxidative phosphorylation, Reduced ability to generate ATP
MIE 1169 Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment of post-translational modification (carboxylation) of osteocalcin Anticoagulant rodenticide interferes with carboxylation of Gla proteins in bone, Impairment
KE 1122 Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failure of secondary hemostasis Under carboxylated clotting factors will not assemble on cell surfaces to form clot, Failur
KE 1130 Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage) Failure in vascular repair mechanisms, Unresolved blood loss (hemorrhage)
KE 1131 Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carboxylation of clotting factors (e.g., des-gamma-carboxy prothrombin) Failure in gamma-glutamyl carboxylation of clotting factors II, VII, IX and X, Under carbo
KE 1132 Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tissue, impaired carbon dioxide and waste product removal Blood loss and development of anemia, Impaired oxygen delivery and nutrient delivery to tis
KE 1133 Hemostasis, Depletion from blood of fully functional carboxylated clotting factors Hemostasis, Depletion from blood of fully functional carboxylated clotting factors
KE 1135 Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction Reduced fitness or even mortality, Acidosis, hypovolemic shock and organ dysfunction
KE 1151 Osteoporosis and vascular calcification, Bone deterioration Osteoporosis and vascular calcification, Bone deterioration
AO 1136 Impaired recruitment , Population trajectory Impaired recruitment , Population trajectory

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
Life stage Evidence
All life stages High

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
humans Homo sapiens High NCBI
Rodentia spp. Rodentia sp. High NCBI
birds Tachycineta bicolor Moderate NCBI
mammals mammals High NCBI

Sex Applicability

The sex for which the AOP is known to be applicable. More help
Sex Evidence
Male
Female

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

Life Stage Applicability, Taxonomic Applicability, Sex Applicability Elaborate on the domains of applicability listed in the summary section above. Specifically, provide the literature supporting, or excluding, certain domains. Female rodents are less sensitive to ARs than males Female humans are more sensitive ti ARs than males

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