In chemico sequential testing strategy for assessing the photoallegic potential

Hayato Nishida; Toshiyuki Ohtake; Takao Ashikaga; Morihiko Hirota; Satomi Onoue; Yoshiki Seto; Yoshiki Tokura; Hirokazu Kouzuki

doi:10.1016/j.tiv.2021.105245

In chemico sequential testing strategy for assessing the photoallegic potential

Toxicol In Vitro. 2021 Dec:77:105245. doi: 10.1016/j.tiv.2021.105245. Epub 2021 Sep 9.

Authors

Hayato Nishida¹, Toshiyuki Ohtake², Takao Ashikaga³, Morihiko Hirota¹, Satomi Onoue⁴, Yoshiki Seto⁴, Yoshiki Tokura⁵, Hirokazu Kouzuki¹

Affiliations

¹ Shiseido Global Innovation Center, 1-2-11, Takashima, Nishi-ku, Yokohama, Kanagawa 220-0011, Japan.
² Shiseido Global Innovation Center, 1-2-11, Takashima, Nishi-ku, Yokohama, Kanagawa 220-0011, Japan. Electronic address: toshiyuki.otake@shiseido.com.
³ Division of Risk Assessment, Center for Biological Safety and Research, National Institute of Health Sciences, 3-25-26 Tonomachi, Kawasaki-ku, Kanagawa 210-9501, Japan.
⁴ Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan.
⁵ Allergic Disease Research Center, Chutoen General Medical Center, 1-1 Shobugaike, Kakegawa, Shizuoka 436-0040, Japan.

PMID: 34509602
DOI: 10.1016/j.tiv.2021.105245

Abstract

Several non-animal testing methods to assess photoallergic potential have been developed so far, while none of them have yet to be validated and regulatory accepted. Currently, some photoreactivity assays such as UV-VIS spectral analysis and ROS assay are generally used for initial photosafety assessments because of their high sensitivity. However, they have a low specificity, generating a high percentage of false positive results, and the development of a follow-up assessment method is desired. Therefore, this study aimed to develop an in chemico photoallergy testing method, photo-direct peptide reactivity assay (photo-DPRA). Based on photosafety information, 34 photoallergens and 16 non-photoallergens were selected and subjected to UV-VIS spectral analysis, ROS/micellar ROS assays, photo-DPRA, sequential testing strategy (STS) consisting of all three methods, and 3T3 neutral red uptake phototoxicity testing (3T3 NRU PT). Combination of the methods addressing the key events of photoallergy exhibited high prediction performance. Our results showed the proposed strategy would be useful to predict the photoallergic potential of chemicals as the follow-up assessment for false positive chemicals by UV/VIS spectral analysis and ROS assay.

Keywords: Photo-DPRA; Photoallergy; Phototoxicity; ROS assay; STS; UV-VIS spectral analysis.

MeSH terms

Dermatitis, Photoallergic / diagnosis*
Dermatitis, Photoallergic / etiology
Dose-Response Relationship, Drug
Drug Hypersensitivity / diagnosis*
Drug Hypersensitivity / etiology
Humans
Light / adverse effects
Reactive Oxygen Species
Sensitivity and Specificity
Spectrophotometry, Ultraviolet

Substances

Reactive Oxygen Species