Utilizing High-Throughput Screening Data, Integrative Toxicological Prioritization Index Score, and Exposure-Activity...

Area of Science:

• Environmental Toxicology
• Endocrinology
• Computational Toxicology

Background:

• Endocrine-active chemicals disrupt metabolism and homeostasis, increasing chronic disease risk.
• Pesticide effects on estrogen, androgen, and thyroid receptors are known, but others are less understood.

Purpose of the Study:

• To comprehensively characterize and prioritize endocrine-active pesticides.
• To evaluate pesticide endocrine-disrupting potentials across 11 nuclear receptors.

Main Methods:

• Utilized exposure-activity ratio (EAR) and toxicological prioritization index (ToxPi).
• Aggregate exposure assessed via Stochastic Human Exposure and Dose Simulation High-Throughput Model (SHEDS-HT).
• In vitro data converted to human oral equivalent doses using in vitro-to-in vivo extrapolation.

Main Results:

• Evaluated endocrine-disrupting potentials using 76 assays across 11 nuclear receptors.
• Derived EARs and ToxPi scores to prioritize 79 food-based pesticides.
• Identified key pesticides requiring further health risk assessment.

Conclusions:

• EAR profiling effectively informs regulatory chemical prioritization.
• This approach supports targeted, in-depth health risk assessments for endocrine-disrupting pesticides.