Pregnancy-specific physiologically-based toxicokinetic models for bisphenol A and bisphenol S

Area of Science:

• Environmental Health
• Toxicology
• Pharmacokinetics

Background:

• Bisphenol S (BPS) is a prevalent environmental chemical detected in humans.
• BPS, like Bisphenol A (BPA), can cross the placenta and affect placental function.
• Existing toxicokinetic models for BPA cannot be directly applied to BPS due to differing properties.

Purpose of the Study:

• To develop pregnancy-specific physiologically based toxicokinetic (p-PBTK) models for both BPA and BPS.
• To utilize a unified model structure for comparing BPA and BPS toxicokinetics during pregnancy.
• To simulate fetal exposure and accumulation of BPA and BPS.

Main Methods:

• Developed nine-compartment p-PBTK models for BPA and BPS.
• Calibrated models using paired maternal and fetal plasma concentration data from pregnant sheep.
• Simulated fetal exposure following daily maternal intake at tolerable daily intake (TDI) levels over two weeks.

Main Results:

• The developed p-PBTK models accurately simulated maternal and fetal BPA and BPS concentrations.
• Simulations demonstrated fetal accumulation of both BPA and BPS with daily maternal exposure.
• Predicted fetal unconjugated BPA levels reached those observed in human cord blood studies.

Conclusions:

• The validated p-PBTK models provide robust predictions of BPA and BPS toxicokinetics during pregnancy.
• These models enhance understanding of fetal exposure to bisphenolic compounds.
• The models serve as a quantitative tool for future risk assessments and related chemical comparisons.