Testing of chemicals

The Adverse Outcome Pathways development programme workplan

 

Project proposals for developing an Adverse Outcome Pathways (AOP) can be sent to the OECD Secretariat using the submission of proposals form. Government representatives, academic experts, industry experts, non-governmental organisations, scientific societies, etc. can submit project proposals. The National co-ordinators of the Test Guidelines programme are also available for queries, and should be informed about proposals submitted. Project proposals are reviewed twice a year and included in the workplan if justified.

List of projects

 

SECTION A: Development of an adverse outcome pathway

Project 1.1: The Adverse Outcome Pathways for Skin Sensitisation Initiated by Covalent Binding to Proteins

Lead:

Inclusion in work plan:

Secretariat + consultant

2011

Project 1.2: The Adverse Outcome Pathways for Partitioning of nonpolar narcotic compounds into cellular membranes leading to decreased physiological performance (formerly the AOP for Nonpolar Narcosis)

Lead:

Inclusion in work plan:

Belgium

2012, update submitted in 2015

Project 1.3: The Adverse Outcome Pathways for Acetylcholinesterase Inhibition

Lead:

Inclusion in work plan:

United States

2012

Project 1.6: The Adverse Outcome Pathways for Embryonic Vascular Disruption and Developmental Defects

Lead:

Inclusion in work plan:

United States

2013

Project 1.7: The Adverse Outcome Pathways for Sustained Activation of Aryl Hydrocarbon Receptor

Lead:

Inclusion in work plan:

BIAC

2013

AOP title: Sustained AhR Activation leading to Rodent Liver Tumour promotion 

Project 1.8: The AOP for Mutagenic Modes of Action for Cancer 

Lead:

Inclusion in work plan:

United StatesBIAC

2014

Project 1.9: The AOP on Upregulation of Thyroid Hormone Catabolism via Activation of Hepatic Nuclear Receptors, and Subsequent Adverse Neurodevelopmental Outcomes in Mammals

Lead:

Inclusion in work plan:

United States

2013

Project 1.10: The AOP on Xenobiotic Induced Inhibition of Thyroperoxidase and Depressed Thyroid Hormone Synthesis and Subsequent Adverse Neurodevelopmental Outcomes in Mammals

Lead:

Inclusion in work plan:

United States

2013

Project 1.11: The AOP for Heritable Germ Cell-Derived Disease

Lead:

Inclusion in work plan:

Canada

2013

AOP 1: Alkylation of DNA in male pre-meiotic germ cells causing inherited mutation - Completed

AOP 2: Chemical interaction with tubulin in oocytes leading to inherited aneuploidy

AOP 3: Stable bulky DNA adducts in male pre-meiotic germ cells causing point mutation leading to inherited DNA sequence mutation

Project 1.12: The AOPs Linking Aromatase Inhibition, Androgen Receptor Agonism, Estrogen Receptor Antagonism, or Steroidogenesis Inhibition, to Impaired Reproduction in Small Repeat-Spawning Fish Species

Lead:

Inclusion in work plan:

United States

2013

AOP 1: Adverse Outcome Pathway on Aromatase Inhibition Leading to Reproductive Dysfunction (in Fish) - Completed

AOP 2: Androgen receptor agonism leadfing to reproductive dysfunction

AOP 3: Estrogen receptor antagonism leading to reproductive dysfunction 

AOP 4: Estrogen receptor antagonism leading to reproductive dysfunction 

AOP 5: Androgen receptor antagonism leading to reproductive dysfunction

Project 1.13: The AOPs on Neurotoxicant-induced Neuroinflammation: a converging key event in an adverse outcome pathway

Lead:

Inclusion in work plan:

Switzerland

2013

AOP1: Binding to SH/selen-proteins can trigger neuroinflammation leading to neurodegeneration

AOP2: Binding of antagonists to NMDAR can trigger neuroinflammation leading to neurodegeneration 

Project 1.15: The AOP for Neurotoxicity induced by GABAA receptor inhibition

Lead:

Inclusion in work plan:

United States

2013

Project 1.16: The AOP describing Hematotoxicity due to Nitroaromatics and N-hydroxyl anilines

Lead:

Inclusion in work plan:

United States

2013

Project 1.17: The AOP on CAR and PPARα-mediated pathways to non-genotoxic rodent liver cancer

Lead:

Inclusion in work plan:

United States

2013

Project 1.18: The AOP on CAR and PXR-mediated pathways to rodent liver hyperplasia

Lead:

Inclusion in work plan:

United States

2013

Project 1.19: The AOP from bile salt export pump inhibition to cholestatic liver injury

Lead:

Inclusion in work plan:

Belgium

2013

Project 1.20: The AOP for Sensitisation of the Respiratory Tract Induced by Covalent Binding to Proteins

Lead:

Inclusion in work plan:

ICAPO

2013

Project 1.21: Three AOPs from peroxisome proliferator-activated receptors (PPARs) activation leading to reproductive toxicity in rodents

Lead:

Inclusion in work plan:

European Commission

2014

AOP1: PPAR alpha activation leading to decreased fertility upon utero exposure in rodent males

AOP2: PPARγ activation leading to decreased fertility in adult female rodents

AOP3: PPARα activation leading to decreased fertility in male rodents 

Project 1.24: The AOP from Cyp2E1 stabilization by substrate binding leading to liver cancer

Lead:

Inclusion in work plan:

Canada

2014

Project 1.25: The AOP from Induction of Secretion of Inflammatory Cytokines Leading to Lung Emphysema

Lead:

Inclusion in work plan:

Canada

2014

Project 1.26: The AOP for Androgen receptor-mediated pathway to liver cancer

Lead:

Inclusion in work plan:

United States

2014

Project 1.27: The AOP linking AhR activation to fish early life stage toxicity

Lead:

Inclusion in work plan:

United States and Canada

2014

Project 1.28: The AOP for Inhibition of Na+/I- symporter (NIS) decreases TH synthesis leading to learning and memory deficit in children

Lead:

Inclusion in work plan:

European Commission

2014

Project 1.29: A catalog of putative AOPs that will enhance the utility of US EPA Toxcast high throughput screening data for hazard identification

Lead:

Inclusion in work plan:

United States

2014

Project 1.30: The AOP describing neurotoxicity due to weakly electrophilic chemicals

Lead:

Inclusion in work plan:

United States

2015

Project 1.31: The AOP for Secondary poisoning of non-target wildlife by anticoagulant rodenticides

Lead:

Inclusion in work plan:

United States

2015

Project 1.32: The AOP From induction of secretion of inflammatory cytokines leading to lung fibrosis

Lead:

Inclusion in work plan:

Canada, ICAPO

2015

Project 1.33: The AOP on binding of inhibitor to the mitochondrial Complex I leads to motor deficit of Parkinson's disease

Lead:

Inclusion in work plan:

European Commission

2015

Project 1.34: The AOP on Blocking of serotonin transporter (SERT) leading to adverse behavioural alterations resulting in population decline in fish

Lead:

Inclusion in work plan:

Switzerland

2015

Project 1.35: The AOP on Thyroperoxidase and/or deiodinase inhibition leading to impaired swim bladder inflation in fish during early life stages

Lead:

Inclusion in work plan:

Belgium

2015

Project 1.36: The AOP on Cytotoxicity leading to nasal tumours

Lead:

Inclusion in work plan:

Japan

2015

Project 1.37: The AOP for 4-HydroxyPhenylPyruvate Dioxygenase (HPPD) Inhibition in Mammals

Lead:

Inclusion in work plan:

UK

2015

Project 1.38: The AOP on Binding of FK506-binding protein 12 (FKBP12) by calcineurin inhibitors leading to immunosuppression

Lead:

Inclusion in work plan:

Japan

2015

Project 1.39: The AOP on Phospholipase A inhibitors leading to hepatotoxicity

Lead:

Inclusion in work plan:

Korea

2015

Project 1.40: The AOP for Kidney dysfunction by decreased thyroid hormone

Lead:

Inclusion in work plan:

Korea

2015

Project 1.41: The AOP on inhibition of thyroid hormone binding to transthyretin and subsequent adverse mammalian developmental neurotoxicity

Lead:

Inclusion in work plan:

ICAPO

2015

 Exposure to Mixtures of Metals and Neurodevelopmental Outcomes

Lead:

Inclusion in work plan:

United States

Project submission under revision

 Project 2.2: The AOP on Hepatotoxicity due to 2,4,6-trinitrotoluene*
Lead:

Inclusion in work plan:

United States

2013

 Project 2.3: The AOP on Energy Metabolism by 2,6-Dinitroluene*

Lead:

Inclusion in work plan:

United States

2013

 Project 2.4: The AOP for Adipogenic phenotype mediated via activation of PPARγ

Lead:

Inclusion in work plan:

United States

2014

 Project 2.5: Percellome Toxicogenomics Approach for AOP Building

Lead:

Inclusion in work plan:

Japan

2014

 Project 2.6: The AOP on Immunosuppression initiated by metal

Lead:

Inclusion in work plan:

Japan

2014

 Project 2.7: The AOP A non-mutagenic mode of action AOP for nasal tumours

Lead:

Inclusion in work plan:

BIAC

2014

AOP1: Intracellular Acidification Induced Olfactory Epithelial Injury Leading to Site of Contact Nasal Tumors

AOP2: Sustained, Severe Glutathione Depletion in Nasal Epithelium Leading to Site of Contact Nasal Tumors

 Project 2.9: The AOP for Arthropathy/Tendinopathy Induced by Fluoroquinolones

Lead:

Inclusion in work plan:

United States

2014

Project 1.42: The Adverse Outcome Pathway on AhR / beta-catenin signalling leading to placental vascular disruption
Lead:

Inclusion in work plan:

Italy

2015

Project 1.43: The Adverse Outcome Pathway on AOP of proximal tubule injury mediated by covalent protein binding and lysosomal overload
Lead:

Inclusion in work plan:

Germany

2016

Project 1.44: The Adverse Outcome Pathway on Adverse Outcome Pathways for cranio-facial skeletal defects
Lead:

Inclusion in work plan:

Italy, Sweden and the Netherlands

2016

Project 1.45: The Adverse Outcome Pathway on Blocking of L-type Ca++ channels leading to heart failure
Lead:

Inclusion in work plan:

UK and European Commission

2016

Project 1.46: The Adverse Outcome Pathway on Hans1 gene dysregulation leading to embryotoxicity
Lead:

Inclusion in work plan:

Japan

2016

Project 1.47: The Adverse Outcome Pathway on Lysosomal damage leading to liver inflammation
Lead:

Inclusion in work plan:

European Commission

2016

Project 1.48: The Adverse Outcome Pathway on Dysregulation of IL-2 transcription leading to immunotoxicity
Lead:

Inclusion in work plan:

Japan

2016

Project 1.49: The Adverse Outcome Pathway on ROS induces phototoxic reactions
Lead:

Inclusion in work plan:

Japan

2016

Project 1.50: The Adverse Outcome Pathway on Oxidative Stress leading to Hypertension
Lead:

Inclusion in work plan:

Tobacco industry

2016

Project 1.51: The Adverse Outcome Pathway on EGFR Activation leading to Mucous Hypersecretion
Lead:

Inclusion in work plan:

Tobacco industry

2016

Project 1.52: The Adverse Outcome Pathway on Histone deacetylase inhibition leading to testicular toxicity

Lead:

Inclusion in work plan:

Japan

2016

Project 1.53: The Adverse Outcome Pathway in utero DNA topoisomerase II inhibition leading to infant leukaemia

Lead:

Inlcusion in work plan:

European Commission/EFSA

2016


 
 

SECTION B: Guidance documents related to adverse outcome pathway development including its evaluation

Project 3.1: Development of a Template for Recording Adverse Outcome Pathways (AOPs) and Associated Guidance Relating to How to Assess its Completeness

Lead:

Inclusion in work plan:

Secretariat

2011

Guidance and template published (No. 184 in OECD Series on Testing and Assessment)

Currently under revision

Users' Handbook released in September 2014

Continuous feed back on the guidance/handbook documents and the wiki have been put in place. 

SECTION C: Knowledge management tool

Project 4.1: Web Based AOP Knowledge Management Tool

Lead:

Inclusion in work plan:

United States

2013

Project 4.2: Adverse Outcome Pathways Knowledge Base (AOP-KB)

Lead:

Inclusion in work plan:

European Commission, United States

2013

Project 4.3: Effectopedia

Lead:

Inclusion in work plan:

EC, US and Secretariat

2013

SECTION D: Others

Project 5.2: Guidance document for describing non-guideline in vitro assays

Lead:

Inclusion in work plan:

VMG-NA

2013

THE PROGRAMME

 

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