A Bioenergetic Framework for Microplastic Accumulation in Human Tissues: A Cellular Turnover Hypothesis.

Micro- and nanoplastics (MNPs) are now pervasive in human tissues, yet their biological behavior remains unexplained within conventional pharmacokinetic frameworks. Here, we propose that MNP distribution may follow a bioenergetic logic governed by cellular turnover and metabolic demand, rather than passive diffusion alone. Integrating the human autopsy literature datasets with programmatic biological parameters suggests that MNPs persist intracellularly and are propagated through cycles of cell death and renewal, establishing a previously unrecognized system of retention-driven recirculation. By integrating tissue-specific metabolic rates, macrophage abundance, and intracellular vulnerability indices across 19 organs, we define a hierarchy of susceptibility, with highest accumulation in the spleen, intestinal epithelium, lung, and bone marrow. This hierarchy maps onto clinical patterns of tissue dysfunction and supports a unifying mechanism in which oxidative stress, energetic instability, and chronic inflammation emerge as convergent responses to MNP burden. We further identify a minimal circulating signature-lactate, high-sensitivity C-reactive protein (hsCRP), and lactate dehydrogenase (LDH)-that reflects systemic bioenergetic disruption associated with MNP exposure. Together, this framework offers a conceptual shift from diffusion-limited to turnover-driven accumulation models, providing testable hypotheses for future prospective validation.