Key Event Title
|Level of Biological Organization|
Key Event Components
Key Event Overview
AOPs Including This Key Event
|AOP Name||Role of event in AOP|
|ROS-mediated chemical phototoxicity||AdverseOutcome|
|All life stages||High|
Key Event Description
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
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
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
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).
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.