Bio: Dr. Xu concurrently serves as:

• Associate Editor-in-Chief of the Asian Journal of Ecotoxicology

• Member of the National Expert Committee on Ecological and Environmental Benchmarks

• Member of Committee on Chemical Risk Prevention & Control. Chinese Society for Environmental Sciences Research Focus on Aquatic Ecotoxicology and Environmental Risk Assessment, specifically focusing on:

• Non-animal testing methods for chemical pollutants

• Toxicokinetic-toxicodynamic (TK-TD) modeling

• Environmental risk assessment methodologies

Major Publications & Achievements:

• Published over 110 peer-reviewed articles in leading journals (ES&T, JHM, etc.)

• Authorized nearly 20 Chinese national invention patents

• Edited or co-authored 4 academic monographs

• Awarded a 2nd Prize for Environmental Protection Scientific and Technological Progress Award

Abstract: : Endocrine disrupting chemicals (EDCs), increasingly detected in various environmental media due to industrial and agricultural activities, can interfere with human and animal endocrine systems, posing risks to human and ecosystem health. High-throughput in vitro assays, combined with in vitro-in vivo extrapolation (IVIVE), enable the use of in vitro responses to predict corresponding in vivo exposures and thresholds of concern. This integrated approach also holds potential for efficiently estimating chemical toxicity to diverse wildlife species, reducing reliance

on animal testing. However, developing wildlife physiologically based toxicokinetic (PBTK) models for ecological IVIVE applications is challenging, particularly for accurately estimating the internal effective dose (biological equivalent concentration, BEC) linked to complex biological pathways and adverse outcomes (AOs) of EDCs. Fish, key vertebrates in freshwater ecosystems, are the most common models in ecotoxicology. We established an enhanced fish PBTK model integrated with an IVIVE approach. This model incorporates parameter optimization for chemical unbound fraction, pH-dependent ionization, and hepatic clearance, along with calibration of temperature effects and growth dilution based physiological models of fish. The fish-PBTK-IVIVE approach provides more precise estimates of tissue-specific concentrations and reasonable approximations of BEC targeting the nuclear receptor binding activity of EDCs. Comparisons with in vivo data showed accurate predictions for most dissociable and non-dissociable EDCs. Furthermore, BECs derived from in vitro fish assays partially characterized the in vivo  dose-response relationships for adverse vision and swimming disorder outcomes. Additionally, the model aids in assessing cross-species variability and sensitivity among fish species. Utilizing IVIVE-derived BECs with target pathways facilitates developing predicted no-effect concentrations (PNECs) for chemicals sharing analogous modes of action (MOA). It is acknowledged that limitations in available in vitro activity data and the number of fish species studied may affect the accuracy of PNECs and species sensitivity extrapolations.

In conclusion, the proposed fish PBTK-IVIVE approach provides valuable information for screening-level ecological risk assessment of EDCs and supports chemical environmental exposure assessment to prioritize testing and monitoring efforts rigorously.