Physiologically based pharmacokinetic (PBPK) tool kit for environmental pollutants--metals

Area of Science:

• Environmental Health
• Toxicology
• Computational Biology

Background:

• The Agency for Toxic Substances and Disease Registry (ATSDR) identifies human exposure levels to environmental pollutants.
• Physiologically Based Pharmacokinetic (PBPK) models are crucial for assessing toxicity via multiple exposure pathways.
• ATSDR is creating a PBPK model tool kit for translational research.

Purpose of the Study:

• To re-code existing PBPK models for priority environmental contaminants into a common simulation language.
• To evaluate the fidelity and sensitivity of the re-coded models.
• To apply the PBPK tool kit for interpreting biomonitoring data.

Main Methods:

• Re-coding published PBPK models for cadmium, mercury, and arsenic.
• Model fidelity evaluation and sensitivity analysis post re-coding.
• Application of the cadmium PBPK model to National Health and Nutrition Examination Survey (NHANES) data.

Main Results:

• Re-coded models for cadmium, mercury, and arsenic showed good agreement with original simulations.
• Sensitivity analysis confirmed model reliability.
• The cadmium PBPK model successfully interpreted NHANES biomonitoring data.

Conclusions:

• The PBPK model tool kit is a valuable resource for ATSDR scientists.
• The tool kit facilitates simulations of environmental pollutant exposures.
• It enhances the interpretation of site-specific biomonitoring data for public health protection.