Advancing ecotoxicological studies: Utilizing new approach methodologies to enable cross-species extrapolation and...

Area of Science:

• Environmental Toxicology
• Pharmacokinetics
• Ecological Risk Assessment

Background:

• Traditional avian toxicity testing poses ethical, economic, and extrapolation challenges.
• New Approach Methodologies (NAMs) offer alternatives for assessing agrochemical risks.
• Physiologically Based Kinetic (PBK) modeling shows promise for avian risk assessment.

Purpose of the Study:

• To demonstrate the utility of PBK modeling for agrochemical risk assessment in avian species.
• To enable dosimetry extrapolations and reduce reliance on traditional in vivo testing.
• To compare thiamethoxam's toxicokinetics across different avian species and exposure routes.

Main Methods:

• Developed PBK models for northern bobwhite, mallard, and laying hen.
• Parameterized and validated models using in vitro and in vivo toxicokinetic data.
• Extrapolated models across species using allometric scaling and simulated internal dose metrics (Cmax, AUC).

Main Results:

• PBK models successfully mapped thiamethoxam's toxicokinetic profiles across species.
• Internal exposure was identified as a key determinant of chronic toxicity.
• Mallards exhibited greater sensitivity to acute oral thiamethoxam exposure.

Conclusions:

• PBK modeling enhances the interpretation of avian toxicity studies.
• This in vitro-in silico approach facilitates more robust ecological risk assessments for agrochemicals.
• NAMs, like PBK modeling, are crucial for advancing avian ecotoxicology and risk assessment.