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Behavioural and metabolomic changes from chronic dietary exposure to low-level deoxynivalenol reveal impact on mouse well-being

Abstract

The mycotoxin deoxynivalenol (DON) has a high global prevalence in grain-based products. Biomarkers of exposure are detectable in most humans and farm animals. Considering the acute emetic and chronic anorexigenic toxicity of DON, maximum levels for food and feed have been implemented by food authorities. The tolerable daily intake (TDI) is 1 µg/kg body weight (bw)/day for the sum of DON and its main derivatives, which was based on the no-observed adverse-effect level (NOAEL) of 100 µg DON/kg bw/day for anorexic effects in rodents. Chronic exposure to a low-DON dose can, however, also cause inflammation and imbalanced neurotransmitter levels. In the present study, we therefore investigated the impact of a 2-week exposure at the NOAEL in mice by performing behavioural experiments, monitoring brain activation by c-Fos expression, and analysing changes in the metabolomes of brain and serum. We found that DON affected neuronal activity and innate behaviour in both male and female mice. Metabolite profiles were differentiable between control and treated mice. The behavioural changes evidenced at NOAEL reduce the safety margin to the established TDI and may be indicative of a risk for human health.

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Acknowledgements

The authors would like to thank Dr. Ipek Yalcin for helpful advice about behavioural experiments and Dr. Pierre Veinante for critical reading of the manuscript. We would also like to thank Dr. Hege Divon at the Norwegian Veterinary Institute (NVI) for funding the consumables and chemical analyses used in the study through FUNtox, a strategic institute program on Fungi and Mycotoxins in a “One Health” perspective. Furthermore, we are very thankful to Dr. Silvio Uhlig in the chemistry section of the NVI for his support in the chemical and metabolomics analyses.

Funding

This project was funded through the bilateral PHC AURORA-program by the Research Council of Norway (Grant Number NFR255406) and Campus France, and in addition the CNRS, the University of Strasbourg and the Norwegian Veterinary Institute.

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Correspondence to Christiane K. Faeste or Dominique Massotte.

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This article does not contain clinical studies or patient data. This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

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Faeste, C.K., Pierre, F., Ivanova, L. et al. Behavioural and metabolomic changes from chronic dietary exposure to low-level deoxynivalenol reveal impact on mouse well-being. Arch Toxicol 93, 2087–2102 (2019). https://doi.org/10.1007/s00204-019-02470-1

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Keywords

  • Deoxynivalenol
  • Chronic administration in mice
  • Anxiety
  • Innate behaviour
  • Brain activation