Toxicity-based toxicokinetic/toxicodynamic assessment for bioaccumulation of polystyrene microplastics in mice

Area of Science:

• Environmental Toxicology
• Mammalian Toxicology
• Computational Toxicology

Background:

• Microplastic (MP) accumulation in organisms is documented, but mechanistic toxicity data in mammals is scarce.
• Understanding MP toxicity in mammals is crucial for human health risk assessment.

Purpose of the Study:

• To mechanistically assess polystyrene (PS)-MP toxicity in mice using toxicity-based toxicokinetic/toxicodynamic (TBTK/TD) modeling.
• To quantify organ-specific bioaccumulation and biomarker responses to PS-MPs in mice.
• To establish a TBTK/TD framework for extrapolating MP health risks from mice to humans.

Main Methods:

• Applied TBTK/TD modeling to a PS-MP-mice system using published datasets.
• Quantified key TBTK parameters for liver, kidney, and gut exposure to 5 and 20 μm PS-MPs.
• Determined threshold concentrations for sensitive biomarkers.

Main Results:

• The gut exhibited the highest bioaccumulation factor (BCF) of ~8 for 5 μm PS-MPs, with a mean residence time of ~17 days.
• Threshold concentrations varied significantly with particle size (5 μm: 8 ± 5 μg g⁻¹ bw; 20 μm: 0.71 ± 0.14 μg g⁻¹ bw).
• Particle size demonstrably influences TK/TD behavior in mice.

Conclusions:

• The developed TBTK/TD framework provides a mechanistic approach to assess MP toxicity in mice.
• Size-specific TK parameters and threshold criteria are essential for accurate MP risk assessment.
• This study offers a valuable tool-kit for extrapolating mammalian MP exposure risks to humans.