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Aop: 17

AOP Title

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Binding of electrophilic chemicals to SH(thiol)-group of proteins and /or to seleno-proteins during brain development leads to impairment of learning and memory

Short name:

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Oxidative stress and Developmental Neurotoxicity

Graphical Representation

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Authors

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Florianne Tschudi-Monnet, Department of Physiology, University of Lausanne, Switzerland, and Swiss Center for Applied Human Toxicology (SCAHT), Florianne.Tschudi-Monnet@unil.ch

Marie-Gabrielle Zurich Fontanellaz, Department of Physiology, University of Lausanne and SCAHT, Switzerland, marie-gabrielle.zurichfontanellaz@unil.ch

Carolina Nunes, Department of Physiology, University of Lausanne, Switzerland, carolina.nunes@unil.ch

Jenny Sandström, SCAHT, Switzerland, jsm.sandstrom@gmail.com

Rex FitzGerald, SCAHT, Switzerland, rex.fitzgerald@unibas.ch

Michael Aschner, Albert Einstein College of Medecine, New York, USA, michael.aschner@einstein.yu.edu

Christoph van Thriel, Department of Toxicology, Leibniz Research Center for working environment and human factors, Dortmund, Germany, Christoph.VanThriel@ruhr-uni-bochum.de

Joao Rocha, Department of Biochemistry and Molecular Biology, Federal University of Santa Maria, jbtrocha@gmail.com

Point of Contact

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Allie Always   (email point of contact)

Contributors

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  • Florianne Tschudi-Monnet
  • Marie-Gabrielle Zurich
  • Allie Always

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite Under Development 1.13 Included in OECD Work Plan


This AOP was last modified on January 14, 2018 22:20

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Revision dates for related pages

Page Revision Date/Time
Binding, SH/seleno proteins November 09, 2017 04:01
N/A, Mitochondrial dysfunction 1 September 16, 2017 10:14
Oxidative Stress May 30, 2017 14:02
Glutamate dyshomeostasis November 09, 2017 04:04
N/A, Cell injury/death September 16, 2017 10:14
N/A, Neuroinflammation September 16, 2017 10:14
Decrease of neuronal network function September 16, 2017 10:14
Impairment, Learning and memory October 26, 2017 05:38
Tissue resident cell activation December 13, 2017 06:18
Increased Pro-inflammatory mediators December 01, 2017 05:12
Binding, SH/seleno proteins leads to N/A, Mitochondrial dysfunction 1 November 09, 2017 04:09
Oxidative Stress leads to Glutamate dyshomeostasis November 09, 2017 04:10
Glutamate dyshomeostasis leads to N/A, Cell injury/death November 09, 2017 04:10
N/A, Cell injury/death leads to N/A, Neuroinflammation May 23, 2017 04:05
N/A, Neuroinflammation leads to N/A, Cell injury/death November 09, 2017 04:11
N/A, Cell injury/death leads to Neuronal network function, Decreased November 09, 2017 04:12
Neuronal network function, Decreased leads to Impairment, Learning and memory May 15, 2017 10:55
Binding, SH/seleno proteins leads to Oxidative Stress November 09, 2017 04:13
Oxidative Stress leads to N/A, Cell injury/death November 09, 2017 04:13
Glutamate dyshomeostasis leads to Neuronal network function, Decreased November 09, 2017 04:14
Methylmercuric(II) chloride November 29, 2016 18:42
Mercuric chloride November 29, 2016 18:42
Acrylamide November 08, 2017 11:15
Acrolein August 15, 2017 09:55

Abstract

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Background (optional)

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Summary of the AOP

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Events: Molecular Initiating Events (MIE)

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Key Events (KE)

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Adverse Outcomes (AO)

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Sequence Type Event ID Title Short name
1 MIE 1487 Binding, SH/seleno proteins Binding, SH/seleno proteins
2 KE 177 N/A, Mitochondrial dysfunction 1 N/A, Mitochondrial dysfunction 1
3 KE 1392 Oxidative Stress Oxidative Stress
4 KE 1488 Glutamate dyshomeostasis Glutamate dyshomeostasis
5 KE 55 N/A, Cell injury/death N/A, Cell injury/death
6 KE 188 N/A, Neuroinflammation N/A, Neuroinflammation
7 KE 1492 Tissue resident cell activation Tissue resident cell activation
8 KE 1493 Increased Pro-inflammatory mediators Increasaed pro-inflammatory mediators
9 KE 386 Decrease of neuronal network function Neuronal network function, Decreased
10 AO 341 Impairment, Learning and memory Impairment, Learning and memory

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Binding, SH/seleno proteins leads to N/A, Mitochondrial dysfunction 1 adjacent
Oxidative Stress leads to Glutamate dyshomeostasis adjacent
Glutamate dyshomeostasis leads to N/A, Cell injury/death adjacent
N/A, Cell injury/death leads to N/A, Neuroinflammation adjacent
N/A, Neuroinflammation leads to N/A, Cell injury/death adjacent
N/A, Cell injury/death leads to Neuronal network function, Decreased adjacent
Neuronal network function, Decreased leads to Impairment, Learning and memory adjacent
Binding, SH/seleno proteins leads to Oxidative Stress non-adjacent
Oxidative Stress leads to N/A, Cell injury/death non-adjacent
Glutamate dyshomeostasis leads to Neuronal network function, Decreased non-adjacent

Network View

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Stressors

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Name Evidence Term
Methylmercuric(II) chloride High
Mercuric chloride High
Acrylamide Moderate
Acrolein Low

Life Stage Applicability

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Life stage Evidence
During brain development

Taxonomic Applicability

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Sex Applicability

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Overall Assessment of the AOP

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Domain of Applicability

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Essentiality of the Key Events

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Evidence Assessment

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Summary Table
Provide an overall summary of the weight of evidence based on the evaluations of the individual linkages from the Key Event Relationship pages.


Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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