Abstract: The 2025 Nobel Prize in Chemistry was awarded for the development of metal-organic frameworks （MOFs）,accelerating the industrial application of crystalline porous materials. However, with the rapid expansion of MOFs, covalent organic frameworks （COFs）, and hydrogen-bonded organic frameworks （HOFs）, life-cycle ecological risk assessment remains severely lagging. Unlike traditional inorganic nanomaterials, the environmental behavior of these three classes of materials is governed by their intrinsic topological structures and dynamic bonding characteristics. This review analyzes their toxic mechanisms along the “exposure-fate-effect” chain and finds significant structure-dependent toxicity： MOFs exhibit a synergistic metal-ligand toxicity highly dependent on the electronic structure of the metal node. Drawing upon Pearson’s hard and soft acids and bases （HSAB） theory, frameworks constructed with borderline acids （e.g., Cu²⁺, Zn²⁺） undergo rapid intracellular dissociation within acidic lysosomes, triggering severe disruption of calcium homeostasis, overproduction of reactive oxygen species （ROS）, and mitochondrial damage. In contrast, MOFs constructed with hard acids （e.g., Zr⁴⁺, Fe³⁺） exhibit superior thermodynamic stability and excellent biocompatibility. Furthermore, COFs present a toxicity profile centered on interfacial binding and genotoxicity. Driven by strong π-π stacking, two-dimensional rigid conjugated nanosheets intercalate into lipid bilayers, thereby producing irreversible membrane damage. These rigid structures also exhibit strong deoxyribonucleic acid （DNA） intercalation into GC-rich grooves, leading to chronic genotoxicity and physical developmental defects such as microcephaly and impaired mandibular ossification. HOFs demonstrate high environmental sensitivity due to their reliance on weak H-bonding networks. Fluctuations in ionic strength or polarity trigger framework collapse and release of highly lipophilic small-molecule ligands. These free ligands rapidly penetrate biological barriers to accumulate in the lipid-rich yolk sac and neural tubes in embryos, resulting in acute neurodevelopmental toxicity and early mortality.Using zebrafish embryos as an in vivo platform and the adverse outcome pathway （AOP） framework,this review discusses the aquatic ecological risks and food-chain transfer potential of these three materials. To address matrix effects caused by the “eco-corona” formed by natural organic matter （NOM） and interference from synthetic residuals, material purity control and standardized exposure conditions should be incorporated into risk assessment to improve the comparability of toxicity data. In response to the current dilemmas of inadequate standardized testing protocols and the lack of long-term exposure data, this review proposes the integration of the safe-by-design （SbD） concept at the earliest stages of material development. Closed-loop regulatory strategies are recommended to mitigate ecological impacts fundamentally. Source reduction can be achieved through topological modifications, such as transitioning from two-dimensional （2D） to three-dimensional （3D） frameworks or employing multidentate chelation to enhance structural inertness. Interfacial passivation via polymer shielding can effectively block non-specific biological adsorption. Finally, the development of quantitative structure-activity relationship （QSAR） prediction models driven by machine learning is highlighted as a core technological breakthrough, thereby providing theoretical support for the green and sustainable production of novel porous materials.

Key words: crystalline porous materials, metal-organic frameworks, covalent organic frameworks, hydrogen-bonding organic frameworks, structure-toxicity relationship, environmental risk assessment