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Research ArticleToxicology

Phototoxic Risk Assessments on Benzophenone Derivatives: Photobiochemical Assessments and Dermal Cassette-Dosing Pharmacokinetic Study

Yoshiki Seto, Hiroto Ohtake, Masashi Kato and Satomi Onoue
Journal of Pharmacology and Experimental Therapeutics August 2015, 354 (2) 195-202; DOI: https://doi.org/10.1124/jpet.115.223644
Yoshiki Seto
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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Hiroto Ohtake
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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Masashi Kato
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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Satomi Onoue
Department of Pharmacokinetics and Pharmacodynamics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
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Abstract

This study aimed to qualify photosafety screening on the basis of photochemical and pharmacokinetic (PK) data on dermally applied chemicals. Six benzophenone derivatives (BZPs) were selected as model compounds, and in vitro photochemical/phototoxic characterization and dermal cassette-dosing PK study were carried out. For comparison, an in vivo phototoxicity test was also conducted. All of the BZPs exhibited strong UVA/UVB absorption with molar extinction coefficients of over 2000 M−1 × cm−1, and benzophenone and ketoprofen exhibited significant reactive oxygen species (ROS) generation upon exposure to simulated sunlight (about 2.0 mW/cm2); however, ROS generation from sulisobenzone and dioxybenzone was negligible. To verify in vitro phototoxicity, a 3T3 neutral red uptake phototoxicity test was carried out, and benzophenone and ketoprofen were categorized to be phototoxic chemicals. The dermal PK parameters of ketoprofen were indicative of the highest dermal distribution of all BZPs tested. On the basis of its in vitro photochemical/phototoxic and PK data, ketoprofen was deduced to be highly phototoxic. The rank of predicted phototoxic risk of BZPs on the basis of the proposed screening strategy was almost in agreement with the results from the in vivo phototoxicity test. The combined use of photochemical and cassette-dosing PK data would provide reliable predictions of phototoxic risk for candidates with high productivity.

Footnotes

    • Received February 13, 2015.
    • Accepted May 21, 2015.
  • This work was supported in part by a Health Labour Sciences Research Grant from the Ministry of Health, Labour, and Welfare, Japan [H25-iyaku-wakate-024]; a grant from the Cosmetology Research Foundation [527]; and a grant from the Hoyu Science Foundation [31].

  • dx.doi.org/10.1124/jpet.115.223644.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 354 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 354, Issue 2
1 Aug 2015
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Research ArticleToxicology

Phototoxic Risk Assessments on Benzophenone Derivatives

Yoshiki Seto, Hiroto Ohtake, Masashi Kato and Satomi Onoue
Journal of Pharmacology and Experimental Therapeutics August 1, 2015, 354 (2) 195-202; DOI: https://doi.org/10.1124/jpet.115.223644

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Research ArticleToxicology

Phototoxic Risk Assessments on Benzophenone Derivatives

Yoshiki Seto, Hiroto Ohtake, Masashi Kato and Satomi Onoue
Journal of Pharmacology and Experimental Therapeutics August 1, 2015, 354 (2) 195-202; DOI: https://doi.org/10.1124/jpet.115.223644
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