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In Silico Modeling Method for Computational Aquatic Toxicology of Endocrine Disruptors: A Software-Based Approach Using QSAR Toolbox
Published on: August 28, 2019
Parameters for pyrethroid insecticide QSAR and PBPK/PD models for human risk assessment
James B Knaak1, Curtis C Dary, Xiaofei Zhang
1Department of Pharmacology and Toxicology, SUNY at Buffalo, Buffalo, NY 14214, USA. jbknaak@aol.com
Summary
This review identifies essential parameters for pyrethroid Quantitative Structure-Activity Relationship (QSAR) and Physiologically Based Pharmacokinetic/Pharmacodynamic (PBPK/PD) models. It highlights data gaps and methods for developing accurate health risk assessments for these insecticides.
Area of Science:
- Toxicology and Pharmacology
- Computational Chemistry
- Environmental Health
Background:
- Pyrethroid insecticides require robust Quantitative Structure-Activity Relationship (QSAR) and Physiologically Based Pharmacokinetic/Pharmacodynamic (PBPK/PD) models for accurate health risk assessment.
- Significant data gaps exist for crucial parameters needed to develop these predictive models, hindering comprehensive risk evaluation.
Purpose of the Study:
- To review and identify the necessary parameters for developing QSAR-PBPK/PD models for pyrethroids.
- To assess the current status of available data and highlight areas requiring further research for model development.
Main Methods:
- Compilation and analysis of existing toxicokinetic, metabolism, and physicochemical data for pyrethroids.
- Identification of chiral isomers, analytical standards, and chromatographic methods (e.g., chiral HPLC) for pyrethroid analysis.
- Evaluation of modeling approaches, including substrate depletion, partition coefficient calculations, and advanced compartmental transit models.
Main Results:
- Rat toxicokinetic studies, metabolism data with labeled pyrethroids, and chiral isomer information are most valuable.
- Resynthesis of analytical standards for metabolites and development of chiral HPLC columns are crucial for future studies.
- Tissue:blood partition coefficients require correction considering plasma protein binding; advanced models are needed for gastrointestinal absorption and dermal penetration.
Conclusions:
- Accurate QSAR-PBPK/PD models for pyrethroids necessitate comprehensive data on metabolism, pharmacokinetics, and physicochemical properties.
- Addressing data gaps, particularly regarding metabolite identification and chiral isomer kinetics, is essential for refining health risk assessments.
- Further research is needed to integrate findings on absorption, distribution, metabolism, and excretion (ADME) into robust PBPK/PD models for human exposure scenarios.
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