Exposure and tissue distribution analyses of brominated flame retardants in Neophocaena phocaenoides through physiologically based toxicokinetic (PBTK) modeling

The Pearl River Delta region in southern China, as a major urban and manufacturing center, receives an elevated burden of brominated flame retardant (BFR) pollution, with its estuary acting as an important sink. Resident cetacean species like Indo-Pacific finless porpoise (Neophocaena phocaenoides) can serve as a bioindicator for the spatiotemporal dynamics of BFRs in the Pearl River Estuary because of their susceptibility to bioaccumulation, but prohibitions on sample collection from living individuals necessitates the development of non-invasive exposure assessment methods. In this study, physiologically based toxicokinetic (PBTK) modeling was used as a non-intrusive tool for assessing the exposure of N. phocaenoides to legacy and novel BFRs. Model-generated data were compared to concentrations detected in various tissue samples collected from stranded individuals (during 2013-2022) for further validation. Temporal trends in prey species concentrations were approximated through modeling-based approaches and observed data from blubber samples. The models were able to approximate the relative tissue distribution patterns of both legacy and novel BFRs, with the highest concentrations found in adipose tissue. Sensitivity analysis indicates that parameters relating to adipose tissue are most likely to affect model outcomes due to its function as the main reservoir of BFRs in vivo. Our PBTK modeling further supports the use of N. phocaenoides as a bioindicator for temporal trends of BFR releases from the Pearl River Delta region. Overall, the developed PBTK modeling can be used to assess the exposure and tissue distribution of legacy and novel BFRs for N. phocaenoides in the Indo-Pacific region.