Genotoxic, Cytotoxic, and Physiological Effects of Nano- and Microplastics in Invertebrate Model Organisms: Mechanistic Integration, Adverse Outcome Pathways, and Multi-Omics Perspectives

Nano- (NPs, <1 µm) and microplastics (MPs, 1 µm–5 mm) are ubiquitous contaminants whose toxicity to invertebrates carries implications at the individual scale and (although not yet quantitatively validated) at the population scale. This semi-systematic narrative review organizes available evidence within an adverse outcome pathway (AOP) framework, linking primary molecular initiating events (MIEs) to adverse outcomes while flagging evidence strength at each step. It involves a structured synthesis that applies selected PRISMA 2020 transparency principles, namely disclosed databases, a priori eligibility criteria, and explicit harvest and de-duplication counts, but does not attempt the exhaustive paired screening, formal risk-of-bias scoring, or quantitative meta-analysis of a full systematic review; this design was chosen because the marked heterogeneity of particle physicochemistry, exposure regimes, and endpoint metrics across the available literature makes pooled statistical synthesis premature. Evidence is appraised across Daphnia, Artemia, Chironomus, Caenorhabditis elegans, Eisenia, marine mollusks, and crustaceans. Polymer chemistry, size, surface charge, weathering, biofilm formation, additives, and adsorbed co-contaminants shape uptake and downstream toxicity. Reactive oxygen species, mitochondrial dysfunction, lysosomal destabilization, and ER stress recur as coupled key events downstream of four MIEs (direct membrane interaction, protein corona formation, surface-catalyzed redox chemistry, and Trojan horse delivery). Multi-omics datasets converge on dysregulated stress, repair, apoptotic, immune, and inflammatory programs; epigenetic marks are increasingly considered as substrates for persistent and potentially heritable toxicity, although stable transgenerational transmission remains poorly demonstrated. The review delivers (i) an AOP map with evidence-strength annotations (strong, moderate, emerging), (ii) a structured cross-study synthesis comparing NP and MP effect profiles, and (iii) a critical layer that reinterprets biphasic and apparently contradictory data as mechanistically informative once particle physicochemistry and tissue context are resolved. Progress will depend on standardized characterization, environmentally realistic mixtures, and AOP-anchored designs that distinguish experimentally demonstrated mechanisms from inferred mechanisms and theoretical extrapolations.