| Mark | Date Date | Title Title | |||
|---|---|---|---|---|---|
| No. 28 | 15 Dec 2022 |
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
This Adverse Outcome Pathway (AOP) describes the linkage between uncoupling of oxidative phosphorylation (OXPHOS) and growth inhibition via decreased cell proliferation. The mitochondrial OXPHOS machinery is a key physiological process responsible... |
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| No. 27 | 15 Dec 2022 |
Chitin synthase 1 inhibition leading to mortality
This Adverse Outcome Pathway (AOP) describes the linkage between Chitin synthase 1 inhibition and mortality in arthropods. In order to grow and develop, arthropods need to shed their exoskeleton (or cuticle) periodically and replace it with a new one... |
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| No. 26 | 15 Dec 2022 |
Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
This Adverse Outcome Pathway (AOP) describes the linkage between Thyroperoxidase inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically... |
|||
| No. 25 | 15 Dec 2022 |
Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 1 inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically... |
|||
| No. 24 | 15 Dec 2022 |
Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 1 inhibition and increased mortality via reduced posterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically... |
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| No. 23 | 15 Dec 2022 |
Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 2 inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically... |
|||
| No. 22 | 15 Dec 2022 |
Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 2 inhibition and increased mortality via reduced posterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically... |
|||
| No. 21 | 15 Dec 2022 |
Inhibitor binding to topoisomerase II leading to infant leukaemia
This Adverse Outcome Pathway (AOP) describes the linkages between the perturbation of the normal topoisomerase II enzyme function and infant leukaemia. Infant leukaemia is a rare haematological disease (1 in 106 newborns, accounting for 10% of all... |
|||
| No. 20 | 15 Dec 2022 |
Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leading to impairment of learning and memory
This Adverse Outcome Pathway (AOP) describes the linkage between binding to proteins involved in protection against oxidative stress and impairment in learning and memory. Production, binding and degradation of Reactive Oxygen Radicals are tightly... |
|||
| No. 19 | 15 Oct 2021 |
Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer
The present AOP describes the prolonged activation of Cyp2E1 resulting in liver cancer. Cyp2E1 is a cytochrome P450 mono-oxygenase that bioactivates over 85 substrates, thereby creating electrophilic metabolites and oxidative stress. Mono-oxygenation... |
|||
| No. 18 | 15 Oct 2021 |
Adverse Outcome Pathway on inhibition of calcineurin activity leading to impaired T-cell dependent antibody response
The present AOP describes the inhibition of calcineurin activity resulting in impaired T-Cell Dependent Antibody Response (TDAR). Calcineurin (CN), a protein phosphatase, is known to impair immune function when its phosphatase activation is... |
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| No. 17 | 15 Oct 2021 |
Adverse Outcome Pathway on histone deacetylase inhibition leading to testicular atrophy
The present AOP describes inhibition of histone deacetylase resulting in testicular atrophy. Histone deacetylase inhibitors (HDIs) are approved as anti-cancer drugs since HDIs have apoptotic effects in cancer cells. The intracellular mechanisms of... |
|||
| No. 16 | 30 Jul 2019 |
Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
Interference with endogenous developmental processes that are regulated by the aryl hydrocarbon receptor (AHR), through sustained exogenous activation, causes molecular, structural, and functional cardiac abnormalities in avian, mammalian and piscine... |
|||
| No. 15 | 30 Jul 2019 |
Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria
Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The... |
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| No. 14 | 30 Jul 2019 |
Adverse Outcome Pathway on inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
The thyroid hormones (TH) are essential for brain development, maturation, and function as they regulate the early key developmental processes. Normal human brain development and cognitive function relays on sufficient production of TH during the... |
|||
| No. 13 | 30 Jul 2019 |
Adverse Outcome Pathway on inhibition of Thyroperoxidase and subsequent adverse neurodevelopmental outcomes in mammals
This AOP describes one adverse outcome that may result from the inhibition of thyroperoxidase (TPO) during mammalian development. Chemical inhibition of TPO results in decreased thyroid hormone (TH) synthesis, and subsequent reduction in circulating... |
|||
| No. 12 | 30 Jul 2019 |
Adverse Outcome Pathway on aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
This AOP details the linkage between activation of the aryl hydrocarbon receptor (AhR) and early life stage mortality in oviparous vertebrates. It can be initiated mostly by dioxin-like compounds, which are able to bind to the AhR causing... |
|||
| No. 11 | 30 Jul 2019 |
Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
This AOP begins with the interaction of chemicals to the picrotoxin binding site of the ionotropic GABA receptor complex causing blockage of the ion channel. As a result, decrease in inward chloride conductance occurs, followed by a reduction in... |
|||
| No. 10 | 30 Jul 2019 |
Adverse Outcome Pathway on antagonist binding to PPARα leading to body-weight loss
The present AOP describes antagonistic chemical binding to the peroxisome proliferator-activated receptor α (PPARα), resulting in preferential binding a co-repressor to the overall PPARα signalling complex causing a chain of events that includes:... |
|||
| No. 9 | 12 Oct 2018 |
Adverse Outcome Pathway on Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
This AOP details the linkage between binding and activation of androgen receptor (AR) in females and reductions in cumulative fecundity and spawning. AR-mediated activities are among the major concerns in endocrine disruptor screening programs.... |
OECD Series on Adverse Outcome Pathways
An Adverse Outcome Pathway (AOP) describes a logical sequence of causally linked events at different levels of biological organisation, which follows exposure to a stressor and leads to an adverse health effect in humans or wildlife. AOPs are the central element of a toxicological knowledge framework, promoted by member countries through OECD, built to support chemical risk assessment based on mechanistic reasoning. These AOPs are available in the AOP-Wiki, an interactive and virtual encyclopaedia for AOP development. Following their development and review, the endorsed AOPs are published in the OECD Series on Adverse Outcome Pathways. As scientific knowledge progresses, the publication of an AOP in this series does not preclude regular updates or new contributions to a given AOP. While the AOP-Wiki is a dynamic tool, only impactful changes to the AOP will be reflected in subsequent updates of the published AOP.
English
- ISSN: 2415170X (online)
- https://doi.org/10.1787/2415170X
1 - 20 of 28 results
Uncoupling of oxidative phosphorylation leading to growth inhibition via decreased cell proliferation
You Song and Daniel L. Villeneuve
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between uncoupling of oxidative phosphorylation (OXPHOS) and growth inhibition via decreased cell proliferation. The mitochondrial OXPHOS machinery is a key physiological process responsible...
Chitin synthase 1 inhibition leading to mortality
Simon Schmid, You Song and Knut Erik Tollefsen
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between Chitin synthase 1 inhibition and mortality in arthropods. In order to grow and develop, arthropods need to shed their exoskeleton (or cuticle) periodically and replace it with a new one...
Thyroperoxidase inhibition leading to increased mortality via reduced anterior swim bladder inflation
Lucia Vergauwen, Evelyn Stinckens, Daniel L. Villeneuve and Dries Knapen
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between Thyroperoxidase inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically...
Deiodinase 1 inhibition leading to increased mortality via reduced anterior swim bladder inflation
Lucia Vergauwen, Evelyn Stinckens, Daniel L. Villeneuve and Dries Knapen
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 1 inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically...
Deiodinase 1 inhibition leading to increased mortality via reduced posterior swim bladder inflation
Lucia Vergauwen, Evelyn Stinckens, Daniel L. Villeneuve and Dries Knapen
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 1 inhibition and increased mortality via reduced posterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically...
Deiodinase 2 inhibition leading to increased mortality via reduced anterior swim bladder inflation
Lucia Vergauwen, Evelyn Stinckens, Daniel L. Villeneuve and Dries Knapen
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 2 inhibition and increased mortality via reduced anterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically...
Deiodinase 2 inhibition leading to increased mortality via reduced posterior swim bladder inflation
Lucia Vergauwen, Evelyn Stinckens, Daniel L. Villeneuve and Dries Knapen
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between Deiodinase 2 inhibition and increased mortality via reduced posterior swim bladder inflation. The swim bladder is a gas-filled organ found in many bony fish species and typically...
Inhibitor binding to topoisomerase II leading to infant leukaemia
Olavi Pelkonen, Andrea Terron, Antonio F. Hernandez, Pablo Menendez and Susanne Hougaard Bennekou
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkages between the perturbation of the normal topoisomerase II enzyme function and infant leukaemia. Infant leukaemia is a rare haematological disease (1 in 106 newborns, accounting for 10% of all...
Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins involved in protection against oxidative stress during brain development leading to impairment of learning and memory
Florianne Tschudi-Monnet, Marie-Gabrielle Zurich, Carolina Nunes, Jenny Sandström, Rex FitzGerald, Michael Aschner and Joao Rocha
15 Dec 2022
This Adverse Outcome Pathway (AOP) describes the linkage between binding to proteins involved in protection against oxidative stress and impairment in learning and memory. Production, binding and degradation of Reactive Oxygen Radicals are tightly...
Adverse Outcome Pathway on Cyp2E1 activation leading to liver cancer
Francina Webster, Iain B. Lambert and Carole L. Yauk
15 Oct 2021
The present AOP describes the prolonged activation of Cyp2E1 resulting in liver cancer. Cyp2E1 is a cytochrome P450 mono-oxygenase that bioactivates over 85 substrates, thereby creating electrophilic metabolites and oxidative stress. Mono-oxygenation...
Adverse Outcome Pathway on inhibition of calcineurin activity leading to impaired T-cell dependent antibody response
Hiroyuki Komatsu, Junichiro Sugimoto, Ken Goto, Kiyoshi Kushima, Naohisa Tsutsui, Shigeru Hisada, Shiho Ito, Tadashi Kosaka, Takumi Ohishi, Yasuharu Otsubo and Yoshihiro Takahashi
15 Oct 2021
The present AOP describes the inhibition of calcineurin activity resulting in impaired T-Cell Dependent Antibody Response (TDAR). Calcineurin (CN), a protein phosphatase, is known to impair immune function when its phosphatase activation is...
Adverse Outcome Pathway on histone deacetylase inhibition leading to testicular atrophy
Shihori Tanabe, Akihiko Hirose and Takashi Yamada
15 Oct 2021
The present AOP describes inhibition of histone deacetylase resulting in testicular atrophy. Histone deacetylase inhibitors (HDIs) are approved as anti-cancer drugs since HDIs have apoptotic effects in cancer cells. The intracellular mechanisms of...
Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to early life stage mortality, via reduced VEGF
Amani Farhat and Sean W. Kennedy
30 Jul 2019
Interference with endogenous developmental processes that are regulated by the aryl hydrocarbon receptor (AHR), through sustained exogenous activation, causes molecular, structural, and functional cardiac abnormalities in avian, mammalian and piscine...
Adverse Outcome Pathway on Aryl hydrocarbon receptor activation leading to uroporphyria
Amani Farhat, Gillian Manning, Jason O’Brien and Sean W. Kennedy
30 Jul 2019
Hepatic uroporphyria is a disorder where the disturbance of heme biosynthesis results in accumulation and excretion of uroporphyrin, heptacarboxyl- and hexacarboxyl porphyrin: collectively referred to as highly carboxylated porphyrins (HCPs). The...
Adverse Outcome Pathway on inhibition of Na+/I- symporter (NIS) leads to learning and memory impairment
Alexandra Rolaki, Francesca Pistollato, Sharon Munn and Anna Bal-Price
30 Jul 2019
The thyroid hormones (TH) are essential for brain development, maturation, and function as they regulate the early key developmental processes. Normal human brain development and cognitive function relays on sufficient production of TH during the...
Adverse Outcome Pathway on inhibition of Thyroperoxidase and subsequent adverse neurodevelopmental outcomes in mammals
Kevin M. Crofton, Mary Gilbert, Katie Paul Friedman, Barbara Demeneix, Mary Sue Marty and R. Thomas Zoeller
30 Jul 2019
This AOP describes one adverse outcome that may result from the inhibition of thyroperoxidase (TPO) during mammalian development. Chemical inhibition of TPO results in decreased thyroid hormone (TH) synthesis, and subsequent reduction in circulating...
Adverse Outcome Pathway on aryl hydrocarbon receptor activation leading to early life stage mortality, via increased COX-2
Jon Doering, Markus Hecker, Daniel L. Villeneuve and Xiaowei Zhang
30 Jul 2019
This AOP details the linkage between activation of the aryl hydrocarbon receptor (AhR) and early life stage mortality in oviparous vertebrates. It can be initiated mostly by dioxin-like compounds, which are able to bind to the AhR causing...
Adverse Outcome Pathway on binding to the picrotoxin site of ionotropic GABA receptors leading to epileptic seizures in adult brain
Ping Gong and Edward J. Perkins
30 Jul 2019
This AOP begins with the interaction of chemicals to the picrotoxin binding site of the ionotropic GABA receptor complex causing blockage of the ion channel. As a result, decrease in inward chloride conductance occurs, followed by a reduction in...
Adverse Outcome Pathway on antagonist binding to PPARα leading to body-weight loss
Kurt A. Gust, Mitchell S. Wilbanks, Zachary A. Collier, Lyle D. Burgoon and Edward J. Perkins
30 Jul 2019
The present AOP describes antagonistic chemical binding to the peroxisome proliferator-activated receptor α (PPARα), resulting in preferential binding a co-repressor to the overall PPARα signalling complex causing a chain of events that includes:...
Adverse Outcome Pathway on Androgen receptor agonism leading to reproductive dysfunction (in repeat-spawning fish)
Daniel L. Villeneuve
12 Oct 2018
This AOP details the linkage between binding and activation of androgen receptor (AR) in females and reductions in cumulative fecundity and spawning. AR-mediated activities are among the major concerns in endocrine disruptor screening programs....