Development of a category approach to predict the testicular toxicity of chemical substances structurally related to ethylene glycol methyl ether

Takashi Yamada, Yushiro Tanaka, Ryuichi Hasegawa, Yuki Sakuratani, Yasushi Yamazoe, Atsushi Ono, Akihiko Hirose, Makoto Hayashi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

We propose a category approach to assessing the testicular toxicity of chemicals with a similar structure to ethylene glycol methyl ether (EGME). Based on toxicity information for EGME and related chemicals and accompanied by adverse outcome pathway information on the testicular toxicity of EGME, this category was defined as chemicals that are metabolized to methoxy- or ethoxyacetic acid, a substance responsible for testicular toxicity. A Japanese chemical inventory was screened using the Hazard Evaluation Support System, which we have developed to support a category approach for predicting the repeated-dose toxicity of chemical substances. Quantitative metabolic information on the related chemicals was then considered, and seventeen chemicals were finally obtained from the inventory as a shortlist for the category. Available data in the literature shows that chemicals for which information is available on the metabolic formation of EGME, ethylene glycol ethyl ether, methoxy- or ethoxyacetic acid do in fact possess testicular toxicity, suggesting that testicular toxicity is a concern, due to metabolic activation, for the remaining chemicals. Our results clearly demonstrate practical utility of AOP-based category approach for predicting repeated-dose toxicity of chemicals.

Original languageEnglish
Pages (from-to)711-719
Number of pages9
JournalRegulatory Toxicology and Pharmacology
Volume70
Issue number3
DOIs
Publication statusPublished - Dec 1 2014
Externally publishedYes

Keywords

  • Adverse outcome pathway
  • Category approach
  • Methoxyacetic acid
  • Repeated-dose toxicity
  • Testicular toxicity

ASJC Scopus subject areas

  • Toxicology

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