Event: 1592

Key Event Title


ROS generation from photoactivated chemicals

Short name


ROS generation

Biological Context


Level of Biological Organization

Cell term


Organ term


Key Event Components


Process Object Action

Key Event Overview

AOPs Including This Key Event


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



Taxonomic Applicability


Term Scientific Term Evidence Link
human Homo sapiens High NCBI

Life Stages


Life stage Evidence
All life stages High

Sex Applicability


Term Evidence
Mixed High

Key Event Description


In the primary event, photoreactive chemicals are excited by the absorption of photon energy.  The energy of the photoactivated chemicals transfer to oxygen and then generates the reactive oxygen species (ROS), including superoxide (O2) via type I reaction and singlet oxygen (1O2) via type II reaction, as principal intermediate species in phototoxic reaction (Foote, 1991, Onoue et al. , 2009).

How It Is Measured or Detected


On the basis of the pathogenesis of drug-induced phototoxicity, a reactive oxygen species (ROS) assay was proposed to evaluate the phototoxic risk of chemicals. The ROS assay can monitor generation of ROS, such as singlet oxygen and superoxide, from photoirradiated chemicals, and the ROS data can be used to evaluate the photoreactivity of chemicals (Onoue et al. , 2014, Onoue et al. , 2013, Onoue and Tsuda, 2006).  The ROS assay is a recommended approach by guidelines to evaluate the phototoxic risk of chemicals (ICH, 2014, PCPC, 2014).

Domain of Applicability


Chemicals: This MIE applies to a wide range of chemicals.  The chemicals absorb photon energy from light within the range of natural sunlight (290-700 nm) (ICH, 2014, Onoue and Tsuda, 2006).

Sex: This MIE applies to both males and females. 

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

Taxonomic: This MIE mainly applies to human.

Evidence for Perturbation by Stressor

Overview for Molecular Initiating Event


Several classes of chemicals cause ROS generation under light exposure, and the ROS generation can be monitored by ROS assay (Onoue et al., 2014, Onoue et al., 2013, Onoue et al. , 2008, Seto et al. , 2013).  The criteria of ROS assay for photosafety assessment of chemicals were defined (Onoue et al., 2014, Onoue et al., 2013).



Foote CS. Definition of type I and type II photosensitized oxidation. Photochem Photobiol. 1991;54:659.

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, Hosoi K, Toda T, Takagi H, Osaki N, Matsumoto Y, et al. Intra-/inter-laboratory validation study on reactive oxygen species assay for chemical photosafety evaluation using two different solar simulators. Toxicology in vitro : an international journal published in association with BIBRA. 2014;28:515-23.

Onoue S, Hosoi K, Wakuri S, Iwase Y, Yamamoto T, Matsuoka N, et al. Establishment and intra-/inter-laboratory validation of a standard protocol of reactive oxygen species assay for chemical photosafety evaluation. Journal of applied toxicology : JAT. 2013;33:1241-50.

Onoue S, Kawamura K, Igarashi N, Zhou Y, Fujikawa M, Yamada H, et al. Reactive oxygen species assay-based risk assessment of drug-induced phototoxicity: classification criteria and application to drug candidates. J Pharm Biomed Anal. 2008;47:967-72.

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.

Onoue S, Tsuda Y. Analytical studies on the prediction of photosensitive/phototoxic potential of pharmaceutical substances. Pharmaceutical research. 2006;23:156-64.

PCPC. PCPC 2014 safety evaluation guidelines; Chapter 7: Evaluation of Photoirritation and Photoallergy potential. Personal Care Products Council; 2014.

Seto Y, Kato M, Yamada S, Onoue S. Development of micellar reactive oxygen species assay for photosafety evaluation of poorly water-soluble chemicals. Toxicology in vitro : an international journal published in association with BIBRA. 2013;27:1838-46.