News Release

Progression from in vivo validation to in vitro screening in hazard
assessment for leukoderma-inducible chemicals
Key Points•6 positive control chemicals with leukoderma in duction potencies and 3
negative control chemicals with leukoderma induction potencies were chosen
based on human case studies.
•6 positive control chemcals induced leukoderma while 3 negative control
chemicals did not validated by in vivo assessment.
•6 possitive and 3 negative control chemicals were correctly distinguished by
the presence or absence of endoplasmic reticulum stress induction inimmortalized normal melanocytes.
Summary
Chemicals are representative environmental factors that affect human health.
Recently, external exposure to a chemical of rhododenol (RD) caused
chemical leukoderma, an acquired patchy hypopigmentation, in about 20,000
Asian people. The development of a hazard assessment system for accurate
determination of leukoderma-inducible chemicals is required for the preventionof such tragedies. Case studies in humans have shown 6 chemicals, including
RD, with a constitutive leukoderma-inducible potency and 3 chemicals with aphotosensitive but not a constitutive leukoderma-inducible potency. In thisstudy, the 6 positive and 3 negative control chemicals with or without
constitutive leukoderma-inducible potencies were investigated by ourpreviously developed in vivo hazard assessment system using tail skin of mice.
Based on the results of validation, this study aimed to develop an in vitro hazard
assessment system to correctly determine chemicals with a constitutive
leukoderma-inducible potency. As expected, external exposure to the 6
positive control chemicals, but not external exposure to the 3 negative control
chemicals, resulted in development of constitutive leukoderma in mouse tailskin with a decreased level of skin melanin and decreased number ofmelanocytes. Moreover, the 6 positive and 3 negative control chemicals werecorrectly distinguished by the presence or absence of endoplasmic reticulum(ER) stress induction, but not by tyrosinase-dependent cell death or productionof reactive oxygen species (ROS), in immortalized normal melanocytes. The
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hazard assessment system using tail skin could be a solid in vivo tool to reliably
determine the chemical potency of a chemical for constitutive leukodermainduction. The hazard assessment system focusing on ER stress induction innormal melanocytes might be a novel and convenient in vitro tool for accurately
evaluating chemicals with leukoderma-inducible potencies. Thus, this study
contributed to environmentology through the development of a screening
system for preventing an environmental factor-related disease.

Publication
Journal name: Environmental Pollution
DOI: 10.1016/j.envpol.2024.124508
Title: Progression from in vivo validation to in vitro screening in hazard
assessment for leukoderma-inducible chemicalsAuthors and Affiliations: Akira Tazaki a,b,c,†, Delgama A. S. M. Nishadhi a,c,†, Ao Li a,c,
Lanyue Zhang a,c, Than Hitke Maw a,c, Lisa Kondo-Ida a,d, Kiyoshi Yanagisawa d,Masashi Kato a,b,ca

Department of Occupational and Environmental Health, Nagoya University

Graduate School of Medicine, Nagoya, Aichi, Japan.
b

Activities of the Institute of Innovation for Future Society of Nagoya University,Aichi, Japan.
cVoluntary Body for International Healthcare in Universities, Nagoya, Aichi,

Japan.
d

Department of Molecular and Cancer Medicine, Fuculty of Pharmacy, Meijo

University, Nagoya, Japan.

Japanese ver.
https://www.med.nagoya-u.ac.jp/medical_J/research/pdf/Env_240806.pdf

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