Characterizing the coverage of critical effects relevant in the safety evaluation of food additives by AOPs

Nynke I. Kramer, Yvette Hoffmans, Siyao Wu, Anette Thiel, Natalie Thatcher, Timothy E.H. Allen, Sara Levorato, Heinz Traussnig, Stefan Schulte, Alan Boobis, Ivonne M.C.M. Rietjens, Mathieu Vinken*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Scopus)


There is considerable interest in adverse outcome pathways (AOPs) as a means of organizing biological and toxicological information to assist in data interpretation and method development. While several chemical sectors have shown considerable progress in applying this approach, this has not been the case in the food sector. In the present study, safety evaluation reports of food additives listed in Annex II of Regulation (EC) No 1333/2008 of the European Union were screened to qualitatively and quantitatively characterize toxicity induced in laboratory animals. The resulting database was used to identify the critical adverse effects used for risk assessment and to investigate whether food additives share common AOPs. Analysis of the database revealed that often such scrutiny of AOPs was not possible or necessary. For 69% of the food additives, the report did not document any adverse effects in studies based on which the safety evaluation was performed. For the remaining 31% of the 326 investigated food additives, critical adverse effects and related points of departure for establishing health-based guidance values could be identified. These mainly involved effects on the liver, kidney, cardiovascular system, lymphatic system, central nervous system and reproductive system. AOPs are available for many of these apical endpoints, albeit to different degrees of maturity. For other adverse outcomes pertinent to food additives, including gastrointestinal irritation and corrosion, AOPs are lacking. Efforts should focus on developing AOPs for these particular endpoints.

Original languageEnglish
Pages (from-to)2115-2125
JournalArchives of Toxicology
Issue number8
Early online date29 Jun 2019
Publication statusPublished - Aug 2019


  • 3Rs
  • Acceptable daily intake
  • Adverse outcome pathway
  • Critical adverse effect
  • Food additives


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