Bioconcentration of perfluorinated alkyl acids: how important is specific binding?

Area of Science:

• Environmental Chemistry
• Toxicology
• Biomolecular Modeling

Background:

• Perfluorinated alkyl acids (PFAAs) are persistent global pollutants with complex pharmacokinetics.
• Protein interactions, including serum albumin, fatty acid-binding proteins (FABPs), and organic anion transporters (OATs), significantly influence PFAA behavior in mammals.
• Similar protein-mediated pharmacokinetics are observed in fish, yet mechanistic models for PFAA bioaccumulation in fish are lacking.

Purpose of the Study:

• To develop and present the first mechanistic protein-binding bioconcentration model for PFAAs in fish.
• To explicitly incorporate protein interactions into a model of PFAA uptake, distribution, and elimination in fish.
• To evaluate the model's accuracy in predicting PFAA bioconcentration and tissue distribution.

Main Methods:

• Developed a mechanistic model considering PFAA uptake via gill diffusion.
• Incorporated protein binding to serum albumin and FABP, and renal transport by OATs.
• Validated the model using existing bioconcentration and tissue distribution data from rainbow trout and common carp.

Main Results:

• The mechanistic protein-binding model accurately predicts PFAA bioconcentration and tissue distribution in fish.
• Comparison with nonspecific partitioning models highlights the critical role of protein interactions.
• The model demonstrates improved accuracy in predicting tissue-specific PFAA levels.

Conclusions:

• Protein interactions are essential for accurately modeling PFAA bioconcentration and tissue distribution in fish.
• The developed model provides a significant advancement over previous nonspecific approaches.
• This mechanistic model offers a robust tool for understanding and predicting PFAA environmental fate and toxicokinetics in aquatic organisms.