Upstream eventROS generation
Oxidation of membrane lipids
Key Event Relationship Overview
AOPs Referencing Relationship
|AOP Name||Adjacency||Weight of Evidence||Quantitative Understanding|
|Reactive oxygen species generated from photoreactive chemicals leading to phototoxic reactions||adjacent||High||Low|
Life Stage Applicability
|All life stages||High|
Key Event Relationship Description
Some photoactivated chemicals can generate reactive oxygen species (ROS) after photoactivation of chemicals by irradiation of light (290–700 nm). ROS generated from photoactivated chemicals can react with membrane lipids and lead to oxidation of membrane lipids.
Evidence Supporting this KER
Photoactivated chemicals generate ROS, and the ROS-generating chemicals cause lipid peroxidation under exposure to light (290–700 nm) in chemical and biological systems (Girotti, 1990, 2001, Onoue and Tsuda, 2006).
Lipid peroxidation was occurred by ROS-generating chemicals under exposure to simulated sunlight (Onoue et al. , 2011, Onoue and Tsuda, 2006).
A photoreactive chemical indicated dose-dependent increases in ROS generation and lipid peroxidation after exposure to a fixed dose of simulated sunlight (Seto et al. , 2013).
Uncertainties and Inconsistencies
Quantitative Understanding of the Linkage
Known modulating factors
Known Feedforward/Feedback loops influencing this KER
Domain of Applicability
Chemicals: This KER applies to a wide range of chemicals. The chemicals absorb photon energy from light within the range of light (290-700 nm) (ICH, 2014, Onoue and Tsuda, 2006).
Sex: This KER applies to both males and females.
Life stages: The relevant life stages for this KER are all life stages after born.
Taxonomic: This KER mainly applies to human.
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.