Mitochondrial alterations associated with zeolitic imidazolate framework-8 nanoparticle-induced reproductive toxicity...

Zeolitic imidazolate framework-8 nanoparticles (ZIF-8), a multifunctional metal-organic framework material with broad application prospects, have attracted increasing attention because of their potential environmental risks. However, their toxicity to terrestrial organisms remains poorly understood. Here, we evaluated the acute toxicity of ZIF-8 to the earthworm Eisenia fetida and compared the toxicological effects of different formulations in a terrestrial exposure system. Following OECD guidelines, a 14-day soil exposure study demonstrated that ZIF-8 exhibited acute toxicity, with the methanol-dispersed formulation showing the lowest LC₅₀ (48.034 mg/kg; median overall survival, OS: 5 days), followed by the dry powder (LC₅₀: 171.730 mg/kg; OS: >12 days) and the aqueous-dispersed formulation (LC₅₀: 240.454 mg/kg; OS: 6 days). Growth inhibition, abnormal behaviors, and surface lesions were observed in all exposure groups, accompanied by reproductive epithelial atrophy, reduced secretory function, and histopathological damage. Ultrastructural examination further revealed mitochondrial swelling, cristae disruption, and numerous electron-dense particle-like structures within the cytoplasm of reproductive epithelial cells. Although these intracellular structures exhibited sizes comparable to those of the synthesized ZIF-8 nanoparticles, their identity could not be definitively confirmed. Overall, our findings indicate that mitochondrial alterations are associated with ZIF-8-induced reproductive injury and may contribute to reproductive epithelial damage. These results provide new evidence for formulation-dependent toxicity of ZIF-8 and contribute to the environmental risk assessment of metal-organic framework nanomaterials in terrestrial ecosystems.