Mark | Date Date | Title Title | |||
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No. 3 | 04 Aug 2016 |
Adverse Outcome Pathway on Alkylation of DNA in Male Pre-Meiotic Germ Cells Leading to Heritable Mutations
Germ cell/heritable mutations are important regulatory endpoints for international agencies interested in protecting the health of future generations. However, germ cell mutation analysis has been hampered by a lack of efficient tools. The motivation... |
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No. 35 | 12 Dec 2023 |
Adverse Outcome Pathway on Androgen receptor agonism leading to male-biased sex ratio
This adverse outcome pathway links androgen receptor agonism in teleost fish during gonadogenesis to male-biased sexual differentiation and consequently, reduced population growth rate. Sex determination in teleost fishes is highly plastic; it can be... |
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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.... |
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No. 4 | 06 Aug 2016 |
Adverse Outcome Pathway on Aromatase Inhibition Leading to Reproductive Dysfunction (in Fish)
This adverse outcome pathway details the linkage between inhibition of gonadal aromatase activity in females and reproductive dysfunction, as measured through the adverse effect of reduced cumulative fecundity and spawning. Initial development of... |
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No. 34 | 12 Dec 2023 |
Adverse Outcome Pathway on Aromatase inhibition leading to male-biased sex ratio via impacts on gonad differentiation
This adverse outcome pathway links inhibition of aromatase activity in teleost fish during gonadogenesis to increased differentiation to testis resulting in a male-biased sex ratio in the population, and ultimately, reduced population sustainability.... |
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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... |
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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. 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... |
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No. 7 | 12 Oct 2018 |
Adverse Outcome Pathway on Inhibition of the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits
This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that... |
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No. 2 | 04 Aug 2016 |
Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis
Liver fibrosis is an important human health issue associated with chemical exposure. It is a typical result of chronic toxic injury and one of the considered endpoints for regulatory purposes. This AOP describes the linkage between hepatic injury... |
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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:... |
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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... |
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No. 6 | 09 Sept 2016 |
Adverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment
Under physiological conditions activation of glutamate ionotropic receptors such as N-methyl-D-aspartate (NMDARs), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPARs) and kainate (KARs) is responsible for basal excitatory synaptic... |
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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... |
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No. 5 | 13 Aug 2016 |
Adverse Outcome Pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
It is well documented and accepted that learning and memory processes rely on physiological functioning of the glutamate receptor N-methyl-D-aspartate (NMDAR). Both animal and human studies investigating NMDA itself, experiments with NMDAR... |
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No. 8 | 12 Oct 2018 |
Adverse Outcome Pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors during brain development leading to neurodegeneration with impairment in learning and memory in aging
This AOP links chronic NMDA receptors inhibition during brain development to neurodegeneration in hippocampus and cortex with amyloid plaque deposition and tau hyperphosphorylation, and impairment of learning and memory, which are considered as... |
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No. 32 | 23 Oct 2023 |
Adverse Outcome Pathway on deposition of energy leading to lung cancer
The present Adverse Outcome Pathway (AOP) describes the linkage between lung cancer initiated from the Deposition of Energy (DoE) into a cell by a prototypic stressor such as radon gas. The multiple ionization events from DoE can directly break DNA... |
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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... |
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No. 30 | 23 Oct 2023 |
Adverse Outcome Pathway on impaired interleukin-1 receptor type I (IL-1R1) signaling leading to impaired T-cell dependent antibody response
Stressors that exhibit immunosuppression might act by different mechanisms, i.e. alter the number of cells involved in the immune response, the ability of the cells to produce cytokines, chemokines, antibodies or growth factors, the composition of... |
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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... |
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 35 results
Adverse Outcome Pathway on Alkylation of DNA in Male Pre-Meiotic Germ Cells Leading to Heritable Mutations
Carole Yauk, Iain Lambert, Francesco Marchetti and George Douglas
04 Aug 2016
Germ cell/heritable mutations are important regulatory endpoints for international agencies interested in protecting the health of future generations. However, germ cell mutation analysis has been hampered by a lack of efficient tools. The motivation...
Adverse Outcome Pathway on Androgen receptor agonism leading to male-biased sex ratio
Kelvin J. Santana Rodriguez, Daniel L. Villeneuve, Kathleen M. Jensen, Gerald T. Ankley and David H. Miller
12 Dec 2023
This adverse outcome pathway links androgen receptor agonism in teleost fish during gonadogenesis to male-biased sexual differentiation and consequently, reduced population growth rate. Sex determination in teleost fishes is highly plastic; it can be...
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....
Adverse Outcome Pathway on Aromatase Inhibition Leading to Reproductive Dysfunction (in Fish)
Daniel L. Villeneuve
06 Aug 2016
This adverse outcome pathway details the linkage between inhibition of gonadal aromatase activity in females and reproductive dysfunction, as measured through the adverse effect of reduced cumulative fecundity and spawning. Initial development of...
Adverse Outcome Pathway on Aromatase inhibition leading to male-biased sex ratio via impacts on gonad differentiation
Kelvin J. Santana Rodriguez, Daniel L. Villeneuve, Kathleen M. Jensen, Gerald T. Ankley and David H. Miller
12 Dec 2023
This adverse outcome pathway links inhibition of aromatase activity in teleost fish during gonadogenesis to increased differentiation to testis resulting in a male-biased sex ratio in the population, and ultimately, reduced population sustainability....
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 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 the mitochondrial complex I of nigro-striatal neurons leading to parkinsonian motor deficits
Anna Bal-Price, Marcel Leist, Stefan Schildknecht, Florianne Tschudi-Monnet, Alicia Paini and Andrea Terron
12 Oct 2018
This AOP describes the linkage between inhibition of complex I (CI) of the mitochondrial respiratory chain and motor deficit as in parkinsonian disorders. Binding of an inhibitor to CI has been defined as the molecular initiating event (MIE) that...
Adverse Outcome Pathway on Protein Alkylation Leading to Liver Fibrosis
Brigitte Landesmann
04 Aug 2016
Liver fibrosis is an important human health issue associated with chemical exposure. It is a typical result of chronic toxic injury and one of the considered endpoints for regulatory purposes. This AOP describes the linkage between hepatic injury...
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 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 of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment
Magdalini Sachana, Sharon Munn and Anna Bal-Price
09 Sept 2016
Under physiological conditions activation of glutamate ionotropic receptors such as N-methyl-D-aspartate (NMDARs), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPARs) and kainate (KARs) is responsible for basal excitatory synaptic...
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 chronic binding of antagonist to N-methyl-D-aspartate receptors (NMDARs) during brain development induces impairment of learning and memory abilities
Magdalini Sachana, Sharon Munn and Anna Bal-Price
13 Aug 2016
It is well documented and accepted that learning and memory processes rely on physiological functioning of the glutamate receptor N-methyl-D-aspartate (NMDAR). Both animal and human studies investigating NMDA itself, experiments with NMDAR...
Adverse Outcome Pathway on chronic binding of antagonist to N-methyl-D-aspartate receptors during brain development leading to neurodegeneration with impairment in learning and memory in aging
Florianne Tschudi-Monnet and Rex FitzGerald
12 Oct 2018
This AOP links chronic NMDA receptors inhibition during brain development to neurodegeneration in hippocampus and cortex with amyloid plaque deposition and tau hyperphosphorylation, and impairment of learning and memory, which are considered as...
Adverse Outcome Pathway on deposition of energy leading to lung cancer
Samantha Sherman, Zakara Said, Baki Sadi, Carole Yauk, Danielle Beaton, Ruth Wilkins, Robert Stainforth, Nadine Adam and Vinita Chauhan
23 Oct 2023
The present Adverse Outcome Pathway (AOP) describes the linkage between lung cancer initiated from the Deposition of Energy (DoE) into a cell by a prototypic stressor such as radon gas. The multiple ionization events from DoE can directly break DNA...
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 impaired interleukin-1 receptor type I (IL-1R1) signaling leading to impaired T-cell dependent antibody response
Yutaka Kimura, Setsuya Aiba, Takao Ashikaga, Takumi Ohishi and Kiyoshi Kushima
23 Oct 2023
Stressors that exhibit immunosuppression might act by different mechanisms, i.e. alter the number of cells involved in the immune response, the ability of the cells to produce cytokines, chemokines, antibodies or growth factors, the composition of...
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...