Staff Publications

  • external user (warningwarning)
  • Log in as
  • language uk
Record number 498227
Title Dose-dependent DNA adduct formation by cinnamaldehyde and other food-borne α,β-unsaturated aldehydes predicted by physiologically based in silico modelling
Author(s) Kiwamoto, R.; Ploeg, D.; Rietjens, I.M.C.M.; Punt, A.
Source Toxicology in Vitro 31 (2016). - ISSN 0887-2333 - p. 114 - 125.
DOI http://dx.doi.org/10.1016/j.tiv.2015.11.014
Department(s) Sub-department of Toxicology
VLAG
WIMEK
Publication type Refereed Article in a scientific journal
Publication year 2016
Keyword(s) Cinnamaldehyde - DNA adducts - Genotoxicity - Physiologically based kinetic/dynamic modelling - α,β-Unsaturated aldehydes
Abstract

Genotoxicity of α,β-unsaturated aldehydes shown in vitro raises a concern for the use of the aldehydes as food flavourings, while at low dose exposures the formation of DNA adducts may be prevented by detoxification. Unlike many α,β-unsaturated aldehydes for which in vivo data are absent, cinnamaldehyde was shown to be not genotoxic or carcinogenic in vivo. The present study aimed at comparing dose-dependent DNA adduct formation by cinnamaldehyde and 18 acyclic food-borne α,β-unsaturated aldehydes using physiologically based kinetic/dynamic (PBK/D) modelling. In rats, cinnamaldehyde was predicted to induce higher DNA adducts levels than 6 out of the 18 α,β-unsaturated aldehydes, indicating that these 6 aldehydes may also test negative in vivo. At the highest cinnamaldehyde dose that tested negative in vivo, cinnamaldehyde was predicted to form at least three orders of magnitude higher levels of DNA adducts than the 18 aldehydes at their respective estimated daily intake. These results suggest that for all the 18 α,β-unsaturated aldehydes DNA adduct formation at doses relevant for human dietary exposure may not raise a concern. The present study illustrates a possible use of physiologically based in silico modelling to facilitate a science-based comparison and read-across on the possible risks posed by DNA reactive agents.

Comments
There are no comments yet. You can post the first one!
Post a comment
 
Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.