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)

Abstract

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.

Mycotoxins in blood and urine of Swedish adolescents—possible associations to food intake and other background characteristics

“…However, the concentrations were in line with other studies (Viegas et al 2018). Toxicity and toxicokinetics in other species have recently been reviewed by Fraeyman (Fraeyman et al 2017) and as an EFSA supporting document (Maranghi et al 2018), which hopefully makes it possible to risk assess enniatins in the near future.…”

The Occurrence and Dietary Exposure Assessment of Mycotoxins, Biogenic Amines, and Heavy Metals in Mould-Ripened Blue Cheeses

“…According to the EFSA CONTAM panel, acute exposure to ENNB does not indicate concern for human health, but that may not be the case in the case of chronic exposure. Based on the repeated-dose ENNB study, the lowest NOAEL has been observed for female mice at 0.18 mg kg −1 bw day −1 for effects on thymus, uterus, and spleen [48]. We converted the NOAEL by applying an interspecies safety factor of 10 to obtain an aRfD of 18 µg kg −1 bw day −1 for humans.…”

Removal of Small Kernels Reduces the Content of Fusarium Mycotoxins in Oat Grain

“…Enns and BEA have shown cytotoxic, genotoxic and immunomodulating effects, as well as toxic effects on reproductive systems [39,40]. These toxins have been reported to accumulate in animal tissues and eggs [41].…”