Physiologically based in silico modelling to examine DNA adduct formation by different food-borne α,ß-unsaturated aldehydes at realistic low dietary exposure levels

Promovendus R (Reiko) Kiwamoto MSc
Promotor IMCM (Ivonne) Rietjens
Copromotor Ans Punt
Organisatie Wageningen University, Sub-department of Toxicology

wo 13 mei 2015 11:00 tot 12:30

Locatie Aula, gebouwnummer 362
Generaal Foulkesweg 1
6703 BG Wageningen


This thesis aimed at determining dose-dependent detoxification and DNA adduct formation of food-borne α,β-unsaturated aldehydes by using a physiologically based in silico modelling (PBK/D modelling) to contribute to the safety assessment of the aldehydes used as food flavourings. Various α,β-unsaturated aldehydes are present in foods as natural constituents or as added flavourings. The aldehydes react with DNA and raise a concern for genotoxicity although formation of DNA adducts may be insignificant because of adequate detoxification. The PBK/D models developed for 18 aldehydes indicated that the DNA adduct formation by the 18 aldehydes is negligible and does not raise a safety concern at their levels of intake as food flavourings. Also, the models supported read-across from cinnamaldehyde, which is known not to be genotoxic in animals, to other aldehydes. Altogether this thesis presented PBK/D modelling as an approach to investigate genotoxicity of DNA reactive compounds in a body without performing animal experiments.