Validation of the (Q)SAR combination approach for mutagenicity prediction of flavor chemicals

Atsushi Ono, Mika Takahashi, Akihiko Hirose, Eiichi Kamata, Tomoko Kawamura, Takeshi Yamazaki, Kyoko Sato, Masami Yamada, Takayuki Fukumoto, Hiroyuki Okamura, Yoshiharu Mirokuji, Masamitsu Honma

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Most exposure levels of flavor in food are considered to be extremely low. If at all, genotoxic properties should be taken into account in safety evaluations. We have recently established a (quantitative) structure-activity relationship, (Q)SAR, combination system, which is composed of three individual models of mutagenicity prediction for industrial chemicals. A decision on mutagenicity is defined as the combination of predictive results from the three models. To validate the utility of our (Q)SAR system for flavor evaluation, we assessed 367 flavor chemicals that had been evaluated mainly by JECFA and for which Ames test results were available. When two or more models gave a positive evaluation, the sensitivity was low (19.4%). In contrast, when one or more models gave a positive evaluation, the sensitivity increased to 47.2%. The contribution of this increased sensitivity was mainly due to the result of the prediction by Derek for Windows, which is a knowledge-based model. Structural analysis of false negatives indicated some common sub-structures. The approach of improving sub-structural alerts could effectively contribute to increasing the predictability of the mutagenicity of flavors, because many flavors possess categorically similar functional sub-structures or are composed of a series of derivatives.

Original languageEnglish
Pages (from-to)1538-1546
Number of pages9
JournalFood and Chemical Toxicology
Volume50
Issue number5
DOIs
Publication statusPublished - May 2012
Externally publishedYes

Fingerprint

mutagenicity
Flavors
flavor
prediction
Quantitative Structure-Activity Relationship
quantitative structure-activity relationships
Industrial chemicals
Ames test
Structural analysis
Safety
Food
Derivatives

Keywords

  • (Quantitative) structure-activity relationship ((Q)SAR)
  • Ames test
  • Flavor
  • Genotoxicity
  • Mutagenicity

ASJC Scopus subject areas

  • Food Science
  • Toxicology

Cite this

Ono, A., Takahashi, M., Hirose, A., Kamata, E., Kawamura, T., Yamazaki, T., ... Honma, M. (2012). Validation of the (Q)SAR combination approach for mutagenicity prediction of flavor chemicals. Food and Chemical Toxicology, 50(5), 1538-1546. https://doi.org/10.1016/j.fct.2012.02.009

Validation of the (Q)SAR combination approach for mutagenicity prediction of flavor chemicals. / Ono, Atsushi; Takahashi, Mika; Hirose, Akihiko; Kamata, Eiichi; Kawamura, Tomoko; Yamazaki, Takeshi; Sato, Kyoko; Yamada, Masami; Fukumoto, Takayuki; Okamura, Hiroyuki; Mirokuji, Yoshiharu; Honma, Masamitsu.

In: Food and Chemical Toxicology, Vol. 50, No. 5, 05.2012, p. 1538-1546.

Research output: Contribution to journalArticle

Ono, A, Takahashi, M, Hirose, A, Kamata, E, Kawamura, T, Yamazaki, T, Sato, K, Yamada, M, Fukumoto, T, Okamura, H, Mirokuji, Y & Honma, M 2012, 'Validation of the (Q)SAR combination approach for mutagenicity prediction of flavor chemicals', Food and Chemical Toxicology, vol. 50, no. 5, pp. 1538-1546. https://doi.org/10.1016/j.fct.2012.02.009
Ono, Atsushi ; Takahashi, Mika ; Hirose, Akihiko ; Kamata, Eiichi ; Kawamura, Tomoko ; Yamazaki, Takeshi ; Sato, Kyoko ; Yamada, Masami ; Fukumoto, Takayuki ; Okamura, Hiroyuki ; Mirokuji, Yoshiharu ; Honma, Masamitsu. / Validation of the (Q)SAR combination approach for mutagenicity prediction of flavor chemicals. In: Food and Chemical Toxicology. 2012 ; Vol. 50, No. 5. pp. 1538-1546.
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