Prioritization of Mycotoxins Based on Their Genotoxic Potential with an In Silico-In Vitro Strategy.

Area of Science:

• Toxicology and Risk Assessment
• Computational Toxicology
• In Vitro Toxicology

Background:

• Widespread human exposure to diverse mycotoxins necessitates efficient prioritization strategies.
• Assessing mycotoxin toxicity requires cost-effective and time-efficient methods.
• Existing methods may not adequately address complex mycotoxin mixtures and metabolic activation.

Purpose of the Study:

• To develop and validate a combined in silico and in vitro strategy for prioritizing mycotoxins based on mutagenicity.
• To assess the toxic potential of 12 mycotoxins using a two-phase approach.
• To evaluate the utility of the SOS/umu test in conjunction with computational tools for mycotoxin risk assessment.

Main Methods:

• Phase 1: Employed expert knowledge-based (DEREK Nexus) and statistical-based (VEGA QSAR) in silico tools to predict mutagenicity.
• Phase 2: Utilized the in vitro SOS/umu assay to confirm in silico predictions and investigate metabolic activation.
• Mycotoxins were structurally clustered into three groups for systematic evaluation.

Main Results:

• In silico analysis successfully classified Group 1 (aflatoxin, sterigmatocystin) as mutagenic and Group 3 (ochratoxin A, zearalenone, fumonisin B1) as non-mutagenic.
• In silico tools provided conflicting results for Group 2 (trichothecenes), indicating limitations and applicability domain issues.
• The SOS/umu test confirmed classifications for Groups 1 and 3, provided insights into metabolic activation, and ultimately classified Group 2 as non-mutagenic.

Conclusions:

• The integrated in silico-in vitro strategy effectively prioritized mycotoxins, correlating well with Ames test data.
• The SOS/umu test serves as a valuable screening tool for mycotoxin mutagenicity, usable with or without metabolic activation.
• Combining in silico and in vitro methods enhances decision-making in mycotoxin risk assessment.