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||KeyEvent|
|All life stages||High|
Key Event Description
Lipid peroxidation of membrane lipids has been considered to be one of the major mechanisms in phototoxic skin responses induced by photoreactive chemicals (Castell et al., 1994, Girotti, 1990, 2001, Onoue et al., 2011, Onoue and Tsuda, 2006, Seto et al., 2013).
How It Is Measured or Detected
An in vitro system using thiobarbituric acid can monitor lipid peroxidation by photoactivated chemicals (Onoue et al., 2011, Onoue and Tsuda, 2006).
Domain of Applicability
Chemicals: This KE applies to a wide range of chemicals. The chemicals generate a reactive species, such as reactive oxygen species, following absorption of photon energy from light within the range of natural sunlight (290-700 nm) (ICH, 2014, Onoue and Tsuda, 2006).
Sex: This KE applies to both males and females.
Life stages: The relevant life stages for this KE are all life stages after born.
Taxonomic: This KE mainly applies to human.
Evidence for Perturbation by Stressor
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.
Girotti AW. Photodynamic lipid peroxidation in biological systems. Photochem Photobiol. 1990;51:497-509.
Girotti AW. Photosensitized oxidation of membrane lipids: reaction pathways, cytotoxic effects, and cytoprotective mechanisms. J Photochem Photobiol B. 2001;63:103-13.
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, Ochi M, Inoue R, Ito H, Hatano T, et al. In vitro photochemical and phototoxicological characterization of major constituents in St. John's Wort (Hypericum perforatum) extracts. Phytochemistry. 2011;72:1814-20.
Onoue S, Tsuda Y. Analytical studies on the prediction of photosensitive/phototoxic potential of pharmaceutical substances. Pharmaceutical research. 2006;23:156-64.
Seto Y, Inoue R, Kato M, Yamada S, Onoue S. Photosafety assessments on pirfenidone: photochemical, photobiological, and pharmacokinetic characterization. J Photochem Photobiol B. 2013;120:44-51.