A new photosafety screening strategy based on in chemico photoreactivity and in vitro skin exposure for dermally-applied chemicals.

Abstract:

:This study involved an attempt to establish a new photosafety screening system for dermally-applied chemicals consisting of a reactive oxygen species (ROS) assay and an in vitro skin permeation test. The ROS assay was undertaken to evaluate photoreactivity of six test compounds, acridine (ACD), furosemide (FSM), hexachlorophene (HCP), 8-methoxypsoralen (MOP), norfloxacin (NFX), and promethazine (PMZ), and the in vitro skin permeation test was conducted to obtain steady-state concentration (Css) values of test compounds in removed rat skin. All test compounds were photoreactive based on ROS generation under simulated sunlight exposure. In particular, ROS generation from ACD was high compared with other test compounds, and photoreactivity of ACD was deduced to be potent. The Css values of ACD, HCP, MOP, and PMZ were over 50 μg/mL, and skin exposure to FSM and NFX was found to be extremely low. Upon these findings, ACD was judged to be highly phototoxic. The rank for phototoxic risk of test compounds based on photoreactivity and in vitro skin exposure was mostly in agreement with outcomes on their in vivo phototoxicity in rats. The proposed strategy, an alternative to animal testing, would be efficacious for photosafety evaluation of drug candidates in early stages of pharmaceutical development.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Iyama Y,Sato H,Seto Y,Onoue S

doi

10.1016/j.toxlet.2019.09.016

subject

Has Abstract

pub_date

2019-12-15 00:00:00

pages

45-52

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(19)30287-5

journal_volume

317

pub_type

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