In vivo toxicity and genotoxicity of beauvericin and enniatins. Combined approach to study in vivo toxicity and genotoxicity of mycotoxins beauvericin (BEA) and enniatin B (ENNB)

Francesca Maranghi (1) , Roberta Tassinari (1) , Laura Narciso (1) , Sabrina Tait (1) , Cinzia Rocca (1) , Gabriella Di Felice (1) , Cinzia Butteroni (1) , Silvia Corinti (1) , Bianca Barletta (1) , Eugenia Cordelli (2) , Francesca Pacchierotti (2) , Patrizia Eleuteri (2) , Paola Villani (2) , Ludovic Le Hégarat (3, 4) , Valérie Fessard (4, 3) , Océane Reale (4, 3)

1 ISS - Istituto Superiore di Sanità = National Institute of Health
2 ENEA - Agenzia Nazionale per le nuove Tecnologie, l’energia e lo sviluppo economico sostenibile = Italian National Agency for New Technologies, Energy and Sustainable Economic Development
3 Unité de Toxicologie des Contaminants
4 ANSES - Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail

Beauvericin (BEA) and Enniatins (ENN) are mycotoxins produced by Fusarium fungi detected in food and feed; there are insufficient data to establish their reference values. To evaluate BEA and ENN oral toxicity, an integrated approach was applied. Among ENN, Enniatin B (ENNB) was selected as test substance. The approach is composed by: i) in vitro and acute in vivo genotoxicity tests; ii) a repeated-dose oral toxicity study focused on genotoxic, immune, endocrine, nervous endpoints and the reproductive/developmental toxicity screening. For BEA, all the genotoxicity endpoints yielded negative results excluding Comet assay in duodenum and kidney after repeated doses. BEA immunotoxicity was observed in female mice, concentrated in number and functional activity of effector T cells in the spleen. Based on the repeated-dose BEA study, the No Observed Adverse Effect Level (NOAEL) for female mice is 1 mg/kg b.w. per day (increased thyroid pycnotic nuclei and endometrial hyperplasia). In males, the NOAEL is 0.1 mg/kg b.w. per day (reduced colloid and altered T4 serum levels). Maternal NOAEL is 0.1 mg/kg b.w. per day (increased thymus weight), developmental NOAEL is 10 mg/kg b.w. per day. For ENNB, the results support a genotoxic effect in bone marrow and liver cells after acute treatment, but not after repeated exposure. Immunotoxic ENNB effects were observed in both genders, suggestive of a suppressive/inhibiting activity particularly evident in males. Based on the repeated-dose ENNB study, the NOAEL for females is 0.18 mg/kg b.w. per day (histomorphometrical effects on thymus, uterus and spleen). In male mice, the NOAEL is 1.8 mg/kg b.w. per day (enterocyte vacuolization in duodenum and increased Reactive Oxygen Species and reduced Glutathione brain levels). The maternal NOAEL is 1.8 mg/kg b.w. per day (decreased white pulp area and increased red/white pulp area ratio in spleen), developmental NOAEL is 18 mg/kg b.w. per day.

Mots clés: beauvericin; enniatin B; Mycotoxin; In-vivo test; immunotoxicity; genotoxicity; Toxicity; Food safety; Feed

Mots clés: mycotoxine; toxicité; génotoxicité; test in-vivo; sécurité des aliments

Domaines: Toxicologie et chaîne alimentaire; Toxicologie végétale et mycotoxicologie

Francesca Maranghi, Roberta Tassinari, Laura Narciso, Sabrina Tait, Cinzia Rocca, et al.. In vivo toxicity and genotoxicity of beauvericin and enniatins. Combined approach to study in vivo toxicity and genotoxicity of mycotoxins beauvericin (BEA) and enniatin B (ENNB). [Research Report] 2018, pp.1-183. ⟨anses-01818576⟩