Physiologically based models for bone-seeking elements. IV. Kinetics of lead disposition in humans

Area of Science:

• Physiology
• Toxicology
• Biomathematics

Background:

• Lead exposure poses significant health risks.
• Accurate modeling of lead disposition is essential for risk assessment.
• Existing models may not fully capture age-dependent lead behavior, particularly in bone.

Purpose of the Study:

• To develop a comprehensive model of lead disposition in humans.
• To explicitly incorporate age-dependent bone characteristics into lead modeling.
• To simulate lead kinetics and compare model predictions with experimental data.

Main Methods:

• Developed a physiologically based pharmacokinetic (PBPK) model for lead.
• Included specific compartments for liver, kidney, well-perfused tissues, poorly perfused tissues, and bone.
• Modeled age-dependent bone volume, composition, and metabolic activity.
• Represented lead transfer rates as functions of plasma lead concentration.
• Modeled erythrocyte binding of lead as capacity-limited.
• Simulated lead exchange between plasma and bone as a series of linked events, including surface exchange and diffusion into bulk bone.
• Incorporated lead incorporation into mineralizing bone and release during bone resorption.
• Validated the model using data from human dietary and inhalation studies.

Main Results:

• The model successfully simulates lead disposition in humans, accounting for various tissues.
• Age-dependent parameters for bone significantly influence lead kinetics.
• The model captures the complex interplay between plasma lead, blood lead, and bone lead.
• Simulations show good agreement with epidemiological and experimental data.

Conclusions:

• The developed model provides a robust framework for understanding human lead disposition.
• Explicitly modeling age-dependent bone dynamics is critical for accurate lead pharmacokinetic predictions.
• This model can be a valuable tool for assessing lead exposure risks and informing public health interventions.