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Chemical safety and biosafety

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 . 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 1.2: 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 1.6: The Adverse Outcome Pathways for Embryonic Vascular Disruption and Developmental Defects

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

Lead:

Inclusion in work plan:

United States/BIAC

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

Lead:

Inclusion in work plan:

Canada

2015

Project 1.35: An AOP network for thyroid hormone system disruption in fish

Lead:

Inclusion in work plan:

Belgium, Denmark, Germany, United States of America

Updated in 2021 (Initially submitted in 2015 with the following title: The AOP on Thyroperoxidase and/or deiodinase inhibition leading to impaired swim bladder inflation in fish during early life stages).

Project 1.36: The AOP on Cytotoxicity leading to nasal tumours

Lead:

Inclusion in work plan:

Japan

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

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 (JRC)

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 1.52: 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:

Inclusion in work plan:

European Commission/EFSA

2016

Project 1.54: PPARγ inactivation leading to lung fibrosis

Lead:

Inclusion in work plan::

Korea

2017

Project 1.55: Secretion of inflammatory cytokines after cellular sensing of the stressor leading to plaque progression

Lead:

Inclusion in work plan:

Denmark

2017

Project 1.56: DNA double strand breaks leading to lung cancer

Lead:

Inclusion in work plan:

Canada

2017

Project 1.58: Wnt ligand stimulation and Wnt signalling activation lead to cancer malignancy

Lead:

Inclusion in work plan:

Japan

2019

Project 1.59: TPO inhibition leading to impaired fertility in fish

Lead:

Inclusion in work plan:

Korea

2019

Project 1.60: Decreased Trypsin activity leading to pancreatic acinar cell tumour formation in rodents

Lead:

Inclusion in work plan:

Japan

2019

Project 1.61: Vitamin D3 receptor activation leading to adrenal pheochromocytoma formation in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.62: Increased low-digestible carbohydrates in the colon leading to adrenal pheochromocytoma formation in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.63: Sodium glucose cotransporter (SGLT1) inhibition leading to adrenal pheochromocytoma formation in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.64: Inhibition of vesicular monoamine transporter (VMAT) leading to adrenal pheochromocytoma formation in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.65: D2 receptor antagonism leading to pituitary tumour in mice

Lead:

Inclusion in work plan:

Japan

2019

Project 1.66: H/K-ATPase (proton pump) inhibition leading to gastric carcinoid tumour formation in rodents

Lead:

Inclusion in work plan:

Japan

2019

Project 1.67: Histamine receptor 2 blockade leading to gastric carcinoid tumour formation in rodents

Lead:

Inclusion in work plan:

Japan

2019

Project 1.68: : GLP-1 receptor activation leading to thyroid C-cell tumours in rodents

Lead:

Inclusion in work plan:

Japan

2019

Project 1.69: Alpha-glucosidase inhibition leading to renal tubular tumours in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.70: Anti-dopaminergic activity leading to pancreatic islet cell tumour in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.71: Increased low-digestible carbohydrates in the colon leading to Leydig cell tumour in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.72: Dopamine agonism/ enhancement leading to Leydig cell tumour in rats

Lead:

Inclusion in work plan:

Japan

2019

Project 1.73:Activation of estrogen receptors in immune cells exacerbates allergic responses

Lead:

Inclusion in work plan:

Japan

2019

Project 1.74: Inhibition of JAK3 leading to impairment of TDAR

Lead:

Inclusion in work plan:

Japan

2019

Project 1.75: Activation of TLR 7 leading to psoriatic skin disease

Lead:

Inclusion in work plan:

Japan

2019

   

Project 1.76: Development of intersecting AOPs that address genetic toxicology endpoints by an expert community

Lead: 

Inclusion in work plan:

US

2019

Project 1.77: Inhibition of retinaldehyde dehydrogenase leads to population decline

Lead:

Inclusion in work plan:

Korea

2019

Project 1.78: Inhibition of tyrosinase leads to decreased population of fish

Lead:

Inclusion in work plan:

Korea

2019

Project 1.79: Early-life stromal estrogen receptor activation by endocrine disrupting chemicals in the mammary gland leading to enhanced cancer risk

Lead:

Inclusion in work plan:

US

2019

Project 1.80: AOPS for RONS and DNA damage leading to increased risk of Breast Cancer

Lead:

Inclusion in work plan:

US

2019

Project 1.81: Inhibition of 5a-reductase leading to impaired fertility in female fish 

Lead:

Inclusion in work plan:

Korea

2019

Project 1.82: Reduced binding of TH to THR in developing brain cells leads to mental retardation due to alteration in white matter

Lead:

Inclusion in work plan:

Germany

2019

Project 1.83: Disrupted laminin-beta1-integrin interaction leading to developmental neurotoxicity

Lead:

Inclusion in work plan:

Germany

2019

Project 1.84: Thyroid receptor antagonism leading to decreased cognitive function

Lead:

Inclusion in work plan:

USA, Germany, ICAPO

2019

Project 1.85: Oxidative Stress-Mediated Lung Fibrosis

Lead:

Inclusion in work plan:

Tobacco Industry

2019

Project 1.86: Frustrated Phagocytosis-induced lung cancer

Lead:

Inclusion in work plan:

Institut National de Recherche et de Sécurité (INRS) - France

2019

Project 1.87: Lung Surfactant function disruption leading to acute lung toxicity

Lead:

Inclusion in work plan:

Denmark (The National Research Centre for the Working Environment)

2019

Project 1.88: Interactions with lung tissues leading to lung fibrosis via a pathway involving Trefoil Factor 2

Lead:

Inclusion in work plan:

SmartNano Tox consortium (Finland, Germany, Ireland, Canada, Denmark)

2020

Project 1.89: The development of AOPs relevant to space flight health outcomes

Lead:

Inclusion in work plan:

Health Canada

2020

Project 1.90: Perturbed androgen signalling leads to short male anogenital distanceoject 1.83: Disrupted laminin-beta1-integrin interaction leading to developmental neurotoxicity

Lead:

Inclusion in work plan:

National Food Institute, Technical University of Denmark

2020

Project 1.91: Binding to voltage gate sodium channel leading to developmental neurotoxic effects (and acute neurotoxicity)

Lead:

Inclusion in work plan:

European food safety authority

2020

Project 1.92: The AOP for mitochondrial dysfunction in aquatic organisms

Lead:

Inclusion in work plan:

Norwegian Institute for Water Research (NIVA)

2021

Project 1.93: AOPs leading to decreased trajectory in fish population

Lead:

Inclusion in work plan:

Korea

2021

Project 1.94: Inhibition of Chitin Synthesis and Chitin Degradation in Arthropods

Lead:

Inclusion in work plan:

Norwegian Institute for Water Research

2021

Project 1.95: Toll-like receptor 4 activation and peroxisome proliferator-activated receptor gamma inactivation leading to pulmonary fibrosis

Lead:

Inclusion in work plan:

Korea Institute of Toxicology

2021

Project 1.96: Submissions received under the CIAO related project (Modelling the pathogenesis of COVID-19 using the Adverse Outcome Pathway framework

Lead:

Inclusion in work plan:

European Commission (JRC), Humane Society International, Physicians Committee for Responsible Medicine

2021

Project 1.97:Inhibition of ALDH1A leads to decreased fertility, females

Lead:

Inclusion in work plan:

Denmark

2021

Project 1.98:Development of an AOP for celiac disease

Lead:

Inclusion in work plan:

European food safety authority

2021

Project 1.99: Inhibition of mitochondrial electron transport chain (ETC) complexes leading to kidney toxicity

Lead:

Inclusion in work plan:

Canada

2021

Project 1.100: Activation of uterine estrogen receptor-alfa leading to endometrial  adenocarcinoma, via epigenetic modulation

Lead:

Inclusion in work plan:

Italy

2022

Project 1.101: Disruption of the sonic hedgehog pathway during development leads to orofacial clefting

Lead:

Inclusion in work plan:

US

2022

Project 1.102: AOP network leading to heart failure and increase in mortality

Lead:

Inclusion in work plan:

Belgium/Austria

2022

Project 1.103: DNA damage and mutations leading to Metastatic Breast Cancer

Lead:

Inclusion in work plan:

India

2022

Project 1.104: Hypothalamic estrogen receptors inhibition leading to ovarian cancer

Lead:

Inclusion in work plan:

India

2022

Project 1.105: Activation of the AhR leading to breast cancer

Lead:

Inclusion in work plan:

France

2022


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, updated in 2018

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

SECTION C: Knowledge management tool

Project 4.4:  Adverse Outcome Pathways Knowledge Base 2.0 (AOP-KB)

Lead:

Inclusion in work plan:

European Commission, US EPA and Secretariat

2017

SECTION D: Others

Project 5.3: Construction of a series of guidance documents for consistent reporting of ‘omics data from various sources

Lead:

Inclusion in work plan:

PHE and University of Birmingham (UoB) - UK/Health Canada/US EPA

2017

THE PROGRAMME

 

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