Human next-generation risk assessment of trichothecene toxicity
Résumé
Trichothecenes are naturally occurring chemicals, produced by fungi, that can be found in contaminated crops. Trichothecenes have the potential to indirectly damage DNA and exacerbate genotoxic effects of genotoxicants. However, genotoxicity data for most trichothecenes are limited and data gaps remain. Here we use the γH2AX/ pH3 assay to evaluate DNA damage in vitro of 13 trichothecenes. Three human cell lines (SH-SY5Y, ACHN, and HepG2) were exposed to each trichothecene (0.001-100 μM) to assess toxicity as models for the brain, kidney, and liver, respectively. Concentration-dependent induction of DNA damage, illustrated by γH2AX induction, was observed for all trichothecenes. In vitro-in vivo extrapolation (IVIVE) modeling was employed to support in vivo equivalent potency ranking and screen for risk potential. Diacetoxyscirpenol, T-2, and HT-2 had the highest genotoxic potency, notably in SH-SY5Y cells. Administered equivalent doses (AEDs) derived from IVIVE were compared against exposure data from French total diet studies to assess risk potential. AEDs derived for T-2 and HT-2 from the SH-SY5Y model were within 100-fold of exposure levels for infants aged one year or less. Overall, the potential for trichothecenes to damage DNA and higher exposures in infants highlights the need to investigate the cumulative effects across the broader trichothecene family.
Mots clés
Trichothecenes
Genotoxicity
Toxicity
H2AX
Mycotoxins
risk assessment
toxicology
fungus
fungi
DNA damage
genotoxicity
in-vitro test
public health
human
crop
food safety
contamination
Trichothécènes
génotoxicité
toxicité
mycotoxines
évaluation des risques
toxicologie
champignon
champignons
dommages à l'ADN
test in vitro
santé publique
humain
culture
sécurité alimentaire
Domaines
Toxicologie| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
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