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Aop: 282

AOP Title

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Reactive oxygen species (ROS) generated from photoirradiated chemicals leading to phototoxic reactions

Short name:

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ROS induces phototoxic reactions

Graphical Representation

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Authors

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Yoshiki Seto, Satomi Onoue

Laboratory of Biophamracy, School of Pharmaceutical Sciences, University of Shizuoka

Corresponding Author: Satomi Onoue

Point of Contact

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Satomi Onoue   (email point of contact)

Contributors

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  • Yoshiki Seto
  • Satomi Onoue

Status

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Author status OECD status OECD project SAAOP status
Under development: Not open for comment. Do not cite


This AOP was last modified on February 11, 2019 19:04

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Revision dates for related pages

Page Revision Date/Time
Absorption of photon energy February 05, 2019 01:39
ROS generation (singlet oxygen and superoxide) February 03, 2019 00:50
Radicals of target chemicals February 03, 2019 00:51
Oxidation of membrane proteins/lipids February 03, 2019 00:52
Denatuation of membrane proteins February 03, 2019 00:53
Oxidation of DNA February 03, 2019 00:53
Formation of DNA photo-adducts February 03, 2019 00:54
Formation of protein photo-adducts February 03, 2019 00:55
Inflamatory events in light-exposed tissues February 05, 2019 01:41
Absorption of photon energy leads to ROS generation February 04, 2019 02:18
Absorption of photon energy leads to Radical generation February 04, 2019 02:22
ROS generation leads to Oxidation of membrane proteins/lipids February 04, 2019 02:22
ROS generation leads to Denatuation of membrane proteins February 04, 2019 02:23
ROS generation leads to Oxidation of DNA February 04, 2019 02:23
Radical generation leads to DNA photo-adducts February 04, 2019 02:23
Radical generation leads to Protein photo-adducts February 04, 2019 02:24
Oxidation of membrane proteins/lipids leads to Inflammatory events February 04, 2019 02:25
Denatuation of membrane proteins leads to Inflammatory events February 04, 2019 02:29
Oxidation of DNA leads to Inflammatory events February 04, 2019 02:29
DNA photo-adducts leads to Inflammatory events February 04, 2019 02:31
Protein photo-adducts leads to Inflammatory events February 04, 2019 02:31

Abstract

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Phototoxicity is an adverse reaction in the light-exposed tissues triggered by normally harmless doses of sunlight [Moore, 1998; Moore 2002].  Recently, high-intensity UV rays from the sun have reached the Earth’s surface with the destruction of the ozone layer, and interest in phototoxic events has increased enormously.  Notably, phototoxic reactions against exogenous agents are caused by the combined effects of environmental light and external agents, including drugs, cosmetics, and foods [Epstein et al., 1983; Stein et al., 2007]. 

In this AOP, the primary trigger for a compound to be considered with respect to potential to create photochemical and photobiological reaction is the absorption of photon energy from light ranging from 290 to 700 nm.  The extent of absorption depends on the wavelength of light and the type of absorbing chromophores in the light-exposed tissues.  A molecule is excited by absorption of photon energy, and the photoactivated molecule induces photochemical reactions via energy transfer (type I photochemical reaction) and free radical generation (type II photochemical reaction).  These photochemical reactions result in generation of radicals and reactive oxygen species, and the reactive species react with biomolecules.  Generated radicals of a target chemical bind to DNA and proteins, resulting in formation of these photo-adducts, and reactive oxygen species, including singlet oxygen and superoxide, induce oxidation of biomolecules.  These key events bring inflammatory events in the light-exposed tissues [Epstein et al., 1985; Quintero et al., 2000; Brendler-Scwaab et al., 2004].

 

This AOP describes the pathway of photochemical toxicity between absorption of photon energy and inflammatory events in light-exposed tissues. 


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
MIE 1591 Absorption of photon energy Absorption of photon energy
MIE 1592 ROS generation (singlet oxygen and superoxide) ROS generation
MIE 1593 Radicals of target chemicals Radical generation
KE 1594 Oxidation of membrane proteins/lipids Oxidation of membrane proteins/lipids
KE 1595 Denatuation of membrane proteins Denatuation of membrane proteins
KE 1596 Oxidation of DNA Oxidation of DNA
KE 1597 Formation of DNA photo-adducts DNA photo-adducts
KE 1598 Formation of protein photo-adducts Protein photo-adducts
AO 1599 Inflamatory events in light-exposed tissues Inflammatory events

Relationships Between Two Key Events
(Including MIEs and AOs)

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Title Adjacency Evidence Quantitative Understanding
Absorption of photon energy leads to ROS generation adjacent High Low
Absorption of photon energy leads to Radical generation adjacent High Low
ROS generation leads to Oxidation of membrane proteins/lipids adjacent High Low
ROS generation leads to Denatuation of membrane proteins adjacent High Low
ROS generation leads to Oxidation of DNA adjacent High Low
Radical generation leads to DNA photo-adducts adjacent High Low
Radical generation leads to Protein photo-adducts adjacent High Low
Oxidation of membrane proteins/lipids leads to Inflammatory events adjacent High Low
Denatuation of membrane proteins leads to Inflammatory events adjacent High Low
Oxidation of DNA leads to Inflammatory events adjacent High Low
DNA photo-adducts leads to Inflammatory events adjacent High Low
Protein photo-adducts leads to Inflammatory events adjacent High Low

Network View

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Stressors

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Life Stage Applicability

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Life stage Evidence
All life stages High

Taxonomic Applicability

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Term Scientific Term Evidence Link
human Homo sapiens High NCBI

Sex Applicability

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Sex Evidence
Mixed High

Overall Assessment of the AOP

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Domain of Applicability

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Chemicals: This AOP applies to a wide range of chemicals.  The characteristics of phototoxic chemicals are recognized as follows: (i) absorption of light within the range of natural sunlight (290-700 nm); (ii) generation of a reactive species following absorption of UV-visible light; (iii) distribution to light-exposed tissues (e.g., skin and eye) (ICH S10).

Sex: This AOP applies to both males and females. 

Life stages: The relevant life stages for this AOP are all life stages after born.

Taxonomic: This AOP mainly applies to human. 


Essentiality of the Key Events

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The essentiality of KEs for this AOP was rated high on the basis of experimental evidence in the investigations related to each of KEs and published guidelines.  For details see the table on “Support for Essentiality of KEs”.


Evidence Assessment

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Quantitative Understanding

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Considerations for Potential Applications of the AOP (optional)

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References

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