API

Event: 1599

Key Event Title

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Inflamatory events in light-exposed tissues

Short name

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Inflammatory events

Biological Context

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Level of Biological Organization
Organ


Organ term

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Key Event Components

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Process Object Action

Key Event Overview


AOPs Including This Key Event

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AOP Name Role of event in AOP
ROS-mediated chemical phototoxicity AdverseOutcome

Stressors

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Taxonomic Applicability

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Term Scientific Term Evidence Link
human Homo sapiens High NCBI

Life Stages

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Life stage Evidence
All life stages High

Sex Applicability

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Term Evidence
Mixed High

Key Event Description

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Photoirritation is frequently characterized as exaggerated sunburn sometimes mediated by oxidative stress in the cell membrane, and hyperpigmentation and desquamation may occur as a residual effect of a phototoxic reaction. Theoretically, if a high concentration of a phototoxic drug accumulates in the skin and the appropriate wavelength of light is present, any individual will develop a phototoxic reaction. In particular, peroxidation of membrane lipid could be induced by some photosensitizers under photo-irradiation, and this photochemical reaction certainly correlates with damage produced in the cell membrane, leading to the skin photoirritation (Castell et al. , 1994, Onoue et al. , 2009).


How It Is Measured or Detected

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Inflammatory events induced by photoreactive chemicals can be detected in vivo phototoxicity testing and photopatch test in clinical (Epstein, 1964, ICH, 2014, Onoue et al., 2009). 


Domain of Applicability

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Chemicals: This AO applies to a wide range of chemicals.  Phototoxic chemicals are recognized to have following characteristics: (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) in ICH S10 guideline for photosafety assessment (ICH, 2014).

Sex: This AO applies to both males and females. 

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

Taxonomic: This AO mainly applies to human.


Evidence for Perturbation by Stressor



Regulatory Significance of the Adverse Outcome

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Inflammatory events in light-exposed tissues are considered to be the endpoint of ROS-mediated chemical phototoxicity, especially photoirritant reactions (ICH, 2014, Onoue et al., 2009). 


References

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Castell JV, Gomez-Lechon MJ, Grassa C, Martinez LA, Miranda MA, Tarrega P. Photodynamic lipid peroxidation by the photosensitizing nonsteroidal antiinflammatory drugs suprofen and tiaprofenic acid. Photochem Photobiol. 1994;59:35-9.

Epstein S. The Photopatch Test; Its Technique, Manifestations, and Significance. Ann Allergy. 1964;22:1-11.

ICH. ICH Guideline S10 Guidance on Photosafety Evaluation of Pharmaceuticals.: International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2014.

Onoue S, Seto Y, Gandy G, Yamada S. Drug-induced phototoxicity; an early in vitro identification of phototoxic potential of new drug entities in drug discovery and development. Current drug safety. 2009;4:123-36.