Mark | Date Date | Title Title | |||
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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. 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... |
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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. 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. 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... |
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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. 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. 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. 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. 1 | 14 Feb 2018 |
Users' Handbook supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways
This document is a supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways (AOPs). It provides focused and practical instructions for both AOP developers and reviewers and is intended to assist in identifying,... |
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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. 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. 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. 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. 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... |
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
21 - 35 of 35 results
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 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 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 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 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 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 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 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 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...
Users' Handbook supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways
OECD
14 Feb 2018
This document is a supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways (AOPs). It provides focused and practical instructions for both AOP developers and reviewers and is intended to assist in identifying,...
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 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 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 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 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...