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Metabolic Profiles of Tetrabromobisphenol A in Humans Extrapolated from Humanized-Liver Mouse Data Using a Simplified
Tomonori Miura1, Shotaro Uehara2, Kazuki Shigeta1
1Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Chemical Research in Toxicology
|November 17, 2020
Summary
Tetrabromobisphenol A (TBBPA), a flame retardant, poses potential health risks. Physiologically based pharmacokinetic (PBPK) models indicate human exposure is well below safety limits, suggesting a wide safety margin.
Area of Science:
- Environmental Science
- Toxicology
- Pharmacokinetics
Background:
- Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant with increasing global prevalence.
- Concerns exist regarding its potential health risks and human exposure levels.
Purpose of the Study:
- To develop and apply physiologically based pharmacokinetic (PBPK) models for estimating human exposure to TBBPA.
- To assess the health risks associated with TBBPA exposure using biomonitoring data and dosimetry estimations.
Main Methods:
- Scaled animal biomonitoring equivalents to humans using allometric scaling factors to create simplified PBPK models.
- Investigated TBBPA metabolism in vivo and in silico hepatic exposures.
- Utilized reverse dosimetry with human PBPK models to estimate daily TBBPA intake from human serum concentrations.
Main Results:
- TBBPA was metabolized to its glucuronide in vivo, with extensive metabolism observed in humanized-liver mice.
- In silico models showed consistency with reported hepatic exposures.
- Estimated daily TBBPA intake in humans was significantly lower than established health benchmark levels, indicating a wide safety margin (4 orders of magnitude).
Conclusions:
- Simplified PBPK models are effective tools for both forward and reverse dosimetry of TBBPA exposure in humans.
- Current estimated human exposure levels to TBBPA are well within safe limits.
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