The Application of a Physiologically Based Toxicokinetic Model in Health Risk Assessment.

Toxicokinetics plays a crucial role in the health risk assessments of xenobiotics. Classical compartmental models are limited in their ability to determine chemical concentrations in specific organs or tissues, particularly target organs or tissues, and their limited interspecific and exposure route extrapolation hinders satisfactory health risk assessment. In contrast, physiologically based toxicokinetic (PBTK) models quantitatively describe the absorption, distribution, metabolism, and excretion of chemicals across various exposure routes and doses in organisms, establishing correlations with toxic effects. Consequently, PBTK models serve as potent tools for extrapolation and provide a theoretical foundation for health risk assessment and management. This review outlines the construction and application of PBTK models in health risk assessment while analyzing their limitations and future perspectives.

Activated Two-Photon Near-Infrared Ratiometric Fluorescent Nanoprobe for ONOO- Detection and Early Diagnosis and Assessment of Liver Injury.

Liver injury poses a serious threat to human health and growing evidence suggests that it is closely associated with a biomarker (peroxynitrite, ONOO-). Therefore, considering that the relationship of ONOO- levels with the occurrence and development of liver injury disease remains a challenge, an urgent need exists to develop a reliable and robust tool for its visual rapid diagnosis and assessment. Herein, a two-photon near-infrared (TP-NIR) ratiometric fluorescent nanoprobe (NTC) based on a fluorescence resonance energy transfer (FRET) strategy was designed, synthesized, and characterized, which had the advantages of good water solubility, low background interference, deep tissue penetration, and high imaging resolution. Specially, NTC was constructed by self-assembly of an alkynyl group of a small-molecule fluorescent probe (NR) via click chemistry grafting onto azide chitosan (natural polymeric nanomaterial). NR contained acceptor 1 (NIR fluorophore) and donor 3 (D-π-A structure of naphthalimide derivative fluorophore) with outstanding TP properties that could be activated by ONOO- for the ratiometric detection of ONOO-. Furthermore, in the presence of ONOO-, NTC exhibited a short response time (∼10 s) and high selectivity and sensitivity toward ONOO- with an excellent detection limit as low as 15.3 nM over other reactive oxygen/nitrogen species. Notably, NTC has been successfully employed for ONOO- detection and imaging in living HepG2 cells, liver injury mice tissues, and mice models with satisfactory results. Thus, the construction of this NTC nanoprobe can provide a robust molecule tool for enabling early diagnosis and assessment of liver injury in the future.