From dietary exposure to systemic toxicity: organ-on-chip and multi-organ microphysiological systems for green food toxicology

Abstract

Food safety assessment must protect diverse human populations from chronic, low-dose, and mixed dietary exposures, yet conventional animal and static cell models often incompletely represent human digestion, metabolism, microbiota, and vulnerable life stages. This critical review maps living Organ-on-chip (OoC) and multi-organ microphysiological system (MPS) studies published through 10 July 2026 that address food contaminants, additives, foodborne toxins or pathogens, particles, and diet-relevant environmental chemicals. Direct food-toxicology evidence was distinguished from route-adjacent studies, transferable validation, and governance evidence, and studies were appraised for exposure realism, organ connectivity, dosimetry, and regulatory readiness. Gut chips demonstrate flow- and route-dependent responses to mycotoxins, dioxins, metals, enterotoxins, and food-relevant particles; liver and placenta models resolve metabolism- and life-stage-specific effects; and gut–liver systems show how translocation can produce distant-organ injury. However, most studies still use purified single agents, short exposures, transformed cell lines, and nominal concentrations, whereas authentic food matrices, digestion, microbiota, chronic mixtures, human benchmarks, and interlaboratory transfer remain uncommon. We therefore define Green Food Toxicology through five auditable dimensions—human relevance, animal independence, exposure-led evidence, resource sustainability, and regulatory utility—and recommend qualifying OoC/MPS for narrowly defined contexts of use within integrated weight-of-evidence assessment rather than treating them as universal animal replacements.