Reverse dosimetry: interpreting trihalomethanes biomonitoring data using physiologically based pharmacokinetic...

Area of Science:

• Environmental Health
• Toxicology
• Pharmacokinetics

Background:

• Biomonitoring data indicate chemical exposure but don't quantify it directly.
• Physiologically based pharmacokinetic (PBPK) modeling offers a method to interpret biomonitoring results.
• Reverse dosimetry integrates PBPK models with exposure data to estimate exposure distributions.

Purpose of the Study:

• To develop PBPK models for trihalomethanes (THMs) using chloroform's model as a framework.
• To estimate population exposure distributions for THMs consistent with biomonitoring data.
• To evaluate potential inhibition of hepatic metabolism among THMs during household exposure.

Main Methods:

• Utilized an existing PBPK model for chloroform.
• Developed new PBPK models for other trihalomethanes (THMs).
• Employed Monte Carlo sampling for pharmacokinetic and exposure pattern variability.
• Assessed hepatic metabolism inhibition under household exposure scenarios.

Main Results:

• Estimated population distributions of THM blood concentrations linked to various exposure patterns.
• Demonstrated PBPK modeling's utility in inferring population exposures from biomonitoring results.
• Showcased the tool's potential for estimating populations exceeding health risk thresholds.

Conclusions:

• PBPK modeling, via reverse dosimetry, is a valuable tool for understanding population exposures from biomonitoring data.
• This approach can link biomonitoring results to specific exposure levels and inform risk assessment.
• The developed models can identify populations at risk based on toxicity levels and measured exposures.