Pollutant distribution in vertebrates across scales: Organs, cells, and organelles

Pollutant accumulation patterns are essential for understanding their toxicity mechanisms and health risks. Accurately identifying pollutant accumulation sites and toxicity targets requires an integrated understanding of their distribution across multiple scales. This review systematically examines recent advances in the multi-scale distribution of environmental pollutants in vertebrates, spanning organ, cellular, and subcellular levels. It highlights the influence of exposure pathways (inhalation, ingestion, dermal) and partition coefficients on pollutant biodistribution, while also emphasizing the uncertainties arising from pollutant biotransformation. Compared to metals and small-molecule organics, nanomaterials (NMs) generally exhibit lower partition coefficients, and their distributions are much susceptible to the exposure pathway. While traditional studies focus on organ-level distribution, emerging high-resolution techniques (e.g., single-cell sequencing) are increasingly revealing pollutant dynamics at the cellular scale. However, only limited studies have explored pollutant distribution at the cell population and subcellular levels. Most research has concentrated on the cellular distribution of pollutants in the blood, intestine, liver, and gill/lung. The remaining works are largely limited to the multi-scale distribution of NMs. Future research should prioritize cross-scale imaging technologies, computational predictive models, and a greater focus on pollutant speciation in blood and subcellular compartments. By bridging the gap between macroscopic accumulation and microscopic toxicity mechanisms, this review provides a framework for advancing risk assessment and targeted interventions in environmental health.