MISC

2013年3月

A category approach to predicting the repeated-dose hepatotoxicity of allyl esters

REGULATORY TOXICOLOGY AND PHARMACOLOGY
  • Takashi Yamada
  • Yushiro Tanaka
  • Ryuichi Hasegawa
  • Yuki Sakuratani
  • Jun Yamada
  • Eiichi Kamata
  • Atsushi Ono
  • Akihiko Hirose
  • Yasushi Yamazoe
  • Ovanes Mekenyan
  • Makoto Hayashi
  • 全て表示

65
2
開始ページ
189
終了ページ
195
記述言語
英語
掲載種別
DOI
10.1016/j.yrtph.2012.12.001
出版者・発行元
ACADEMIC PRESS INC ELSEVIER SCIENCE

We tested a category approach to predict the hepatotoxic effects of repeated doses of allyl esters using a new database for repeated-dose toxicity. Based on information on hepatotoxic mechanism of allyl acetate, the category was defined as allyl esters that are hydrolyzed to allyl alcohol. Allyl alcohol is readily oxidized to acrolein in the liver, causing hepatotoxicity. Seventeen marketed allyl esters were obtained and grouped into category by identifying or predicting allyl alcohol formation. Allyl esters with a saturated straight alkyl carboxylic acid moiety (allyl acetate, hexanoate and heptanoate as tested species, and allyl butyrate, pentanoate, octanoate, nonanoate and decanoate as untested species) are likely similar in rate of ester hydrolysis, thereby defining subcategory 1. NOAEL and LOAEL for the hepatotoxic effects were estimated at 0.12 and 0.25 mmol/kg/d for the untested species, based on those of allyl acetate. The remaining nine allyl esters with other alkyl or aromatic carboxylic acid moieties were placed in subcategory 2: their hepatotoxicity levels were not predictable due to an unclear match between their degree of structural complexity and rate of hydrolysis. Our results demonstrate the usefulness of the category approach for predicting the hepatotoxicity of untested allyl esters with saturated straight alkyl chains. (C) 2012 Elsevier Inc. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/j.yrtph.2012.12.001
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23246603
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000315429200002&DestApp=WOS_CPL
URL
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84872409885&origin=inward
ID情報
  • DOI : 10.1016/j.yrtph.2012.12.001
  • ISSN : 0273-2300
  • ORCIDのPut Code : 54809840
  • PubMed ID : 23246603
  • SCOPUS ID : 84872409885
  • Web of Science ID : WOS:000315429200002

エクスポート
BibTeX RIS