Strategic photosafety screening system consisting of in chemico photoreactivity and in vitro skin exposure for quinolone derivatives

Iyama, Yosuke; Sato, Hideyuki; Seto, Yoshiki; Onoue, Satomi

doi:10.1016/j.ejps.2020.105257

Cited by 1 publication

(1 citation statement)

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“…To improve the reliability of the photosafety testing of complex materials, as well as their photoreactivity, the pharmacokinetic behavior of major components should also be assessed with a focus on absorption, distribution to UV-exposed tissues, and skin penetration and retention. In our previous investigation, a number of potent phototoxins in humans exhibited significant permeation and accumulation in the skin, and even photoreactive chemicals with low transdermal absorbability tended to show a low phototoxic potential in animal testing (Seto et al, 2012(Seto et al, , 2020Iyama et al, 2020Iyama et al, , 2019. Thus, the combined use of the ROS assay at aMw of 250 and a pharmacokinetic study would be efficacious to make reliable photosafety predictions on the complex materials.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species (ROS) assay-based photosafety screening for complex ingredients: Modification of the ROS assay protocol

et al. 2022

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A reactive oxygen species (ROS) assay has been widely used for photosafety assessment; however, the phototoxic potential of complex materials, including plant extracts, essential oils, and functional polymers, is unevaluable because of their undefined molecular weights. The present study was undertaken to modify the ROS assay protocol for evaluating phototoxic potentials of those materials with use of their apparent molecular weight (aMw). On preparing sample solutions for the ROS assay, aMw ranging from 150 to 350 was tentatively employed for test substances. The modified ROS assays were applied to 45 phototoxic and 19 non-phototoxic substances, including 44 chemicals and 20 complex materials (plant extracts) for clarification of the predictive performance. Generation of ROS from photo-irradiated samples tended to increase as aMW grew, resulting in the largest number of false-positive predictions at aMW of 350. Some false-negative predictions were also observed when aMW was set at 200 or less. At aMw of 250, all tested phototoxic substances could be correctly identified as photoreactive with no false-negative predictions. Based on these observations, aMw of 250 was found to be suitable for the ROS assay on complex materials, and the sensitivity, specificity, and positive and negative predictivity for the proposed ROS assay were calculated to be 100, 52.6, 83.3, and 100%, respectively. Thus, the proposed approach may be efficacious for predicting phototoxic potentials of complex materials and contribute to the development of new products with a wide photosafety margin.

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Section: Discussionmentioning

confidence: 99%