Toxicological Research

Korean Society of Toxicology & Korea Environmental Mutagen Society (한국독성학회)
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Evaluation of the skin phototoxicity of systemically administered pharmaceuticals in Sprague-Dawley rats

  • Kim, Eun Ji (Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Youn, Nam Hee (Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Yi, Jung-Sun (Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Kim, Joo Hwan (Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Cho, Ye-Jin (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Nam, Ki Taek (Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Park, Ki Sook (Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety) ;
  • Lee, Jong Kwon (Toxicological Evaluation and Research Department, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety)
  • Received : 2020.08.13
  • Accepted : 2020.12.04
  • Published : 2021.10.15
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Abstract

In vivo phototoxicity testing is important for predicting drug-induced phototoxicity in humans. Currently, there is no internationally validated in vivo test method for the photosafety evaluation of pharmaceuticals. In this study, we evaluated the phototoxicity of systemically administered drugs using SD rats. We first determined the appropriate ultraviolet A (UVA) dose using 8-methoxypsoralen, a well-known phototoxic drug. Compared to lower and higher UVA doses, we found that a UVA dose of 10 J/cm2 allowed for the detection of phototoxic responses in both a dose- and time-dependent manner. We next performed a phototoxicity study using seven pharmaceutical drugs which included known phototoxic and non-phototoxic drugs using a UVA dose of 10 J/cm2. In order to improve the accuracy of our assessment, we evaluated both gross skin findings as well as histopathological findings. Using gross skin findings alone resulted in an accuracy of 85.7% which could be increased to 100% accuracy when the gross skin findings were combined with histopathological findings. This study suggests that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of systemically administered drugs in SD rats. In conclusion, we found that for studying drug-induced phytotoxicity, a 10 J/cm2 UVA dose serves as the optimal radiation dose, and that the inclusion of histopathological findings increases the accuracy of the phototoxicity evaluation of the drugs.

Keywords

Acknowledgement

This research was supported by the Ministry of Food and Drug Safety of Korea in 2017-2018 (grant numbers 17181MFDS402). We would like to thank Editage (www.editage.co.kr) for English language editing.

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