Environment International (Oct 2024)
Novel insights into the mechanisms of bioaccumulation and tissue-specific distribution of hexafluoropropylene oxide homologues, novel PFOA alternatives, in zebrafish (Danio rerio)
Abstract
Hexafluoropropylene oxide trimer acid (HFPO-TA) and hexafluoropropylene oxide tetramer acid (HFPO-TeA) are two novel alternatives of perfluorooctanoic acid (PFOA). However, their toxicokinetics and accumulation mechanisms in fish are still unknown. This study provides the first line of in vivo uptake and depuration kinetic, bioaccumulation mechanism and tissue-specific distribution for HFPO-TA and HFPO-TeA, upon a 28-day water exposure and a 14-day depuration in zebrafish (Danio rerio). HFPO-TeA and HFPO-TA could quickly accumulate in zebrafish, and the highest concentrations of HFPO-TeA (15.4 ± 1.6 nmol/g ww), HFPO-TA (4.95 ± 0.19 nmol/g ww) and PFOA (0.47 ± 0.03 nmol/g ww) were consistently present in the blood, which was followed by liver, kidney, intestine, gill, gonad and brain, while the lowest were observed in the muscle (1.01 ± 0.11, 0.16 ± 0.02, and 0.01 ± 0.001 nmol/g ww, respectively), indicating both higher accumulation potentials of both HFPO homologs than their predecessor PFOA. The tissue protein content, rather than lipid content, played an enhancing role in the enrichment of three target chemicals, exhibiting a significant positive correlation (r = 0.735, p = 0.038 for HFPO-TeA; r = 0.770, p = 0.026 for HFPO-TA and r = 0.942, p = 0.001 for PFOA) between the tissue bioconcentration factor (BCF) and the protein contents in corresponding tissues. This phenomenon was validated by the equilibrium dialysis experiment, molecular docking analysis and molecular dynamics simulation, which consistently indicated that the binding affinities of serum and liver proteins were greatest with HFPO-TeA, followed by HFPO-TA and least with PFOA. These results suggested that the binding of the target chemicals to specific proteins determined their tissue-specific accumulation potentials. Nontarget screening by high resolution mass spectrometry (HRMS) did not identify suspicious degradation products for HFPO-TA, implying the strong persistence of HFPO-TA in fish.
