A Case Study with Triazole Fungicides to Explore Practical Application of Next-Generation Hazard Assessment Methods...

Area of Science:

• Environmental Toxicology
• Chemical Risk Assessment
• Computational Toxicology

Background:

• Chemical risk assessment is evolving with sophisticated nonanimal models for hazard characterization.
• A pragmatic approach is explored for implementing these new concepts in risk assessment.

Purpose of the Study:

• To evaluate a pragmatic approach for chemical risk assessment using nonanimal models.
• To assess the utility of in silico and in vitro methods for hazard identification and mechanism elucidation.

Main Methods:

• Case study using three triazole fungicides: flusilazole, propiconazole, and cyproconazole.
• Integration of in silico tools, literature-derived high-throughput screening assays, and computational elaborations.
• Targeted in vitro tests to confirm toxicity mechanisms and generate points of departure.

Main Results:

• Nonanimal methods provided adequate qualitative hazard information for risk assessment when compared to traditional in vivo testing.
• The proposed strategy effectively identified potential toxicological mechanisms and targets.
• The approach successfully evaluated the overall level of concern by comparing exposure estimates to toxicological potential.

Conclusions:

• Nonanimal methods are suitable for hazard identification in chemical risk assessment.
• Toxicological mechanisms should guide the selection of assays for next-generation risk assessment.
• Further refinement of the nonanimal testing toolbox, toxicokinetics, and exposure models is necessary.