The influence of cation exchange on the possible mechanism of erionite toxicity: A synchrotron-based micro-X-ray fluorescence study on THP-1-derived macrophages exposed to erionite-Na.

Fibrous erionite is the only zeolite classified as Group 1 carcinogen by the International Agency for Research on Cancer (IARC). Carcinogenesis induced by erionite is thought to involve several factors as biopersistence, the iron role and cation exchange processes. To better understand these mechanisms, a detailed investigation at the micro scale was performed, collecting elemental information on iron and cation release and their distribution in biological systems by synchrotron micro-X-ray fluorescence mapping (SR-micro-XRF) and synchrotron micro-X-ray absorption spectroscopy (SR-micro-XANES) at the TwinMic beamline (Elettra synchrotron) and at the ID21 beamline of the European Synchrotron Radiation Facility (ESRF). By microscopy and chemical mapping, highly detailed maps of the chemical and morphological interaction of biological systems with fibres could be produced. In detail, THP-1 cell line derived macrophages, used as in vitro model, were analysed during erionite-Na phagocytosis at different time intervals, after single dose exposure. For comparison, cellular fluorescent probes were also used to evaluate the intracellular free sodium and calcium concentrations. Synchrotron analyses visualised the spatial distribution of both fibre and mineral particle associated metals during the phagocytosis, describing the mechanism of internalisation of erionite-Na and its accessory mineral phases. The intracellular distribution of metals and other cations was mapped to evaluate metal release, speciation changes and/or cation exchange during phagocytosis. The fluorescent probes complemented microchemical data clarifying, and confirming, the cation distribution observed in the SR-micro-XRF maps. The significant cytoplasmic calcium decrease, and the concomitant sodium increase, after the fibre phagocytosis seemed due to activation of plasma membrane cations exchangers triggered by the internalisation while, surprisingly, the ion-exchange capacity of erionite-Na could play a minor role in the disruption of the two cations intracellular homeostasis. These results help to elucidate the role of cations in the toxicity of erionite-treated THP-1 macrophages and add knowledge to its carcinogenicity process.

Effect of zeolites on the reduction of the ecotoxicity of carbamazepine in the environment.

In this study, the impact of calcination of zeolites on the ecotoxicity of carbamazepine solutions in two matrices, water and synthetic sewage, was assessed. Two types of zeolites were tested: natural zeolite, in the form of a zeolite rock consisting mainly of clinoptilolite, and a synthetic zeolite type 5 A. Additionally, zeolites were calcined at a temperature of 200 °C. The kinetics of carbamazepine adsorption in aqueous solutions and in synthetic sewage matrix was determined. Higher adsorption capacity was obtained for carbamazepine aqueous solutions as well as zeolites after the calcination process. Considering type of zeolite, the highest and fastest uptake of carbamazepine was observed for natural zeolite after calcination. In the case of ecotoxicity, carbamazepine solutions before adsorption was the most toxic towards Raphidocelis subcapitata, next Aliivibrio fischeri and Daphnia magna, regardless to the matrix type. The differentiation in toxicity regarding the type of matrix was observed, in the case of algae and bacteria, higher toxicity was demonstrated by carbamazepine solutions in the water matrix, while in the case of crustaceans-the sewage matrix. After the adsorption process, the toxicity of carbamazepine solutions on zeolites decreased by 34.5-60.9 % for R. subcapitata, 33-39 % for A. fischeri and 55-60 % for D. magna, thus confirming the effectiveness of the proposed method of carbamazepine immobilization.

Persistence and Recovery of ZIF-8 and ZIF-67 Phytotoxicity.

Zeolitic imidazolate frameworks (ZIFs) have been developed quickly and have attracted considerable attention for use in the detection and removal of various pollutants. Understanding the environmental risks of ZIFs is a prerequisite to their safe application by industry and new chemical registration by governments; however, the persistence and recovery of toxicity induced by ZIFs remain largely unclear. This study finds that typical ZIFs (e.g., ZIF-8 and ZIF-67) at a concentration of 0.01-1 mg/L induce significant algal growth inhibition, plasmolysis, membrane permeability, chloroplast damage, and chlorophyll biosynthesis, and the above alterations are recoverable. Unexpectedly, a persistent decrease in reactive oxygen species (ROS) is observed due to the quenching of hydroxyl free radicals. The adverse effects of ZIF-8 are weak and easily alleviated compared with those of ZIF-67. ZIF-8 is internalized mainly by caveolae-mediated endocytosis, while ZIF-67 is internalized mainly by clathrin-mediated endocytosis. Omics studies reveal that the downregulation of mRNA associated with oxidative phosphorylation and the inhibition of chlorophyll and adenosine triphosphate (ATP) synthesis in mitochondria are related to the persistence of phytotoxicity. These findings highlight the phenomena and mechanisms of the persistence and recovery of phytotoxicity, indicating the need to reconsider the environmental risk assessments of ZIFs.

A Comparative Analysis of In Vitro Toxicity of Synthetic Zeolites on IMR-90 Human Lung Fibroblast Cells.

Broad industrial application of zeolites increases the opportunity of inhalation. However, the potential impact of different types and compositions of zeolite on cytotoxicity is still unknown. Four types of synthetic zeolites have been prepared for assessing the effect on lung fibroblast: two zeolite L (LTL-R and LTL-D), ZSM-5 (MFI-S), and faujasite (FAU-S). The cytotoxicity of zeolites on human lung fibroblast (IMR-90) was assessed using WST1 cell proliferation assay, mitochondrial function, membrane leakage of lactate dehydrogenase, reduced glutathione levels, and mitochondrial membrane potential were assessed under control. Intracellular changes were examined using transmission electron microscopy (TEM). Toxicity-related gene expressions were evaluated by PCR array. The result showed significantly higher toxicity in IMR-90 cells with FAU-S than LTL-R, LTL-D and MFI-S exposure. TEM showed FAU-S, spheroidal zeolite with a low Si/Al ratio, was readily internalized forming numerous phagosomes in IMR-90 cells, while the largest and disc-shaped zeolites showed the lowest toxicity and were located in submembranous phagosomes in IMR-90 cells. Differential expression of TNF related genes was detected using PCR arrays and confirmed using qRT-PCR analysis of selected genes. Collectively, the exposure of different zeolites shows different toxicity on IMR-90 cells.

Cyto-genotoxic and inflammatory effects of commercial Linde Type A (LTA) nanozeolites on human alveolar epithelial cells.

Nanozeolites (NZs) are increasingly used in several sectors, including catalysts, ion exchange materials or thermal isolators, taking advantage of the major property of NZs to absorb residual water and moisture to preserve the insulation of devices and products, but very few data are available on their toxicity. We investigated the potential cyto-genotoxicity and pro-inflammatory effects of manufactured Linde Type A (LTA)-NZs on human alveolar cells (A549) exposed to 10, 25, 50 and 100 µg/mL. LTA NZs were characterized by dynamic light scattering (DLS). Cell viability, mortality and apoptosis were evaluated by cytofluorimetric assay after 24h exposure. Membrane damage was evaluated by lactate dehydrogenase release and direct and oxidative DNA damage induction by formamide-pyrimidine glycosylase-Comet assay after 4 and 24 h. The induction of pro-inflammatory effects was evaluated in terms of interleukin 6 (IL-6) and IL-8 cytokine release after 24 h by ELISA. We found a slight increase in apoptotic cell percentage at 50 and 100 µg/mL and dead cell percentage at 100 µg/mL after 24 h; slight, but statistically significant, direct DNA damage starting from 25 µg/mL and slight oxidative DNA damage both at 4 and at 24 h; increased release of IL-6 only at the lowest concentration after 24 h. The results show lack of cytotoxicity, early moderate genotoxicity and slight inflammatory effects at the lowest used concentration. These findings represent the first data on potential genotoxic, oxidative and inflammatory effects of LTA NZs and highlight the need to perform further studies to confirm such results.

Characterization of pulmonary responses in mice to asbestos/asbestiform fibers using gene expression profiles.

Humans exposed to asbestos and/or asbestiform fibers are at high risk of developing many lung diseases including asbestosis, lung cancer, and malignant mesothelioma. However, the disease-causing potential and specific metabolic mechanisms and pathways associated with various asbestos/asbestiform fiber exposures triggering different carcinogenic and non-carcinogenic outcomes are still largely unknown. The aim of this this study was to investigate gene expression profiles and inflammatory responses to different asbestos/asbestiform fibers at the acute/sub-acute phase that may be related to delayed pathological outcomes observed at later time points. Mice were exposed to asbestos (crocidolite, tremolite asbestos), asbestiform fibers (erionite), and a low pathogenicity mineral fiber (wollastonite) using oropharyngeal aspiration. Similarities in inflammatory and tissue damage responses, albeit with quantitative differences, were observed at day 1 and 7 post treatment. Exposure to different fibers induced significant changes in regulation and release of a number of inflammatory cytokines/chemokines. Comparative analysis of changes in gene regulation in the lung on day 7 post exposure were interpretable in the context of differential biological responses that were consistent with histopathological findings at days 7 and 56 post treatment. Our results noted differences in the magnitudes of pulmonary responses and gene regulation consistent with pathological alterations induced by exposures to four asbestos/asbestiform fibers examined. Further comparative mechanistic studies linking early responses with the long-term endpoints may be instrumental to understanding triggering mechanisms underlying pulmonary carcinogenesis, that is lung cancer versus mesothelioma.

Geological occurrence, mineralogical characterization, and risk assessment of potentially carcinogenic erionite in Italy.

Erionite is a zeolite representing a well-known health hazard. In fact, exposure of humans to its fibers has been unequivocally associated with occurrence of malignant mesothelioma. For this reason, a multi-methodological approach, based upon field investigation, morphological characterization, scanning electron microscopy (SEM)/energy-dispersive spectroscopy (EDS) chemical analysis, and structure refinement through X-ray powder diffraction (XRPD), was applied to different samples of potentially carcinogenic erionite from Northern Italy. The studied crystals have a chemical composition ranging from erionite-Ca to erionite-Na and display variable morphologies, varying from prismatic, through acicular and fibrous, to extremely fibrous asbestiform habits. The fibrous samples were characterized by an unusual preferred partition of aluminum (Al) at tetrahedral site T1 instead of tetrahedral site T2. Further, a mismatch between the a-parameter of erionite-Ca and levyne-Ca that are intergrown in the asbestiform sample was detected. This misfit was coupled to a relevant micro-strain to maintain structure coherency at the boundary. Erionite occurs in 65% of the investigated sites, with an estimated quantity of 10 to 40 vol% of the associated minerals. The presence of this mineral is of concern for risk to human health, especially if one considers the vast number of quarries and mining-related activities that are operating in the zeolite host rocks. The discovery of fibrous and asbestiform erionite in Northern Italy suggests the need for a detailed risk assessment in all Italian areas showing the same potential hazard, with specific studies such as a quantification of the potentially respirable airborne fibers and targeted epidemiological surveillance.

Cytotoxicity of Postmodified Zeolitic Imidazolate Framework-90 (ZIF-90) Nanocrystals: Correlation between Functionality and Toxicity.

Using a simple method, the aldehyde groups of zeolitic imidazolate framework-90 (ZIF-90) nanocrystals were converted into carboxyl, amino, and thiol groups, without affecting the integrity of the framework. Notably, for the first time, correlations between functionality and cytotoxicity are also demonstrated via in vitro cytotoxicity assays. The positive charged aminated-ZIF-90 presumably results in either perturbation of cell membrane, more efficient cell uptake, or both. Therefore, the half-maximal effective (EC50 ) concentration of aminated-ZIF-90 has a higher cytotoxicity of about 30 µg mL(-1) .

A mesothelioma epidemic in Cappadocia: scientific developments and unexpected social outcomes.

In Cappadocia, Turkey, an unprecedented mesothelioma epidemic causes 50% of all deaths in three small villages. Initially linked solely to the exposure to a fibrous mineral, erionite, recent studies by scientists from Turkey and the United States have shown that erionite causes mesothelioma mostly in families that are genetically predisposed to mineral fibre carcinogenesis. This manuscript reports, through the eyes of one of the researchers, the resulting scientific advances that have come from these studies and the social improvements that were brought about by both the scientists and members of the Turkish Government.

The role of key genes and pathways involved in the tumorigenesis of Malignant Mesothelioma.

Malignant Mesothelioma (MM) is a very aggressive cancer with low survival rates and often diagnosed at an advanced stage. Several players have been implicated in the development of this cancer, such as asbestos, erionite and the simian virus 40 (SV40). Here, we have reviewed the involvement of erionite, SV40, as well as, the role of several genes (p16(INK4a), p14(ARF), NF2, LATS2, SAV, CTNNB1 and among others), the pathways (RAS, PI3K, Wnt, BCL and Hippo), and their respective roles in the development of MM.

High incidence of lung cancer and malignant mesothelioma linked to erionite fibre exposure in a rural community in Central Mexico.

OBJECTIVE: To report the high incidence of lung cancer (LC) and malignant mesothelioma (MM) linked to environmental exposure to erionite fibres in a rural village of central Mexico. METHODS: This is a retrospective survey of clinical and mortality records from the years 2000-2012, accompanied by an environmental survey for nine Group-1 lung and pleura carcinogenic agents listed by the International Agency for Research on Cancer (IARC). RESULTS: Out of a total of 45 deaths between 2000 and 2012, 14 deaths correspond to different neoplasms of the lung, and at least four deaths to MM. The ages at diagnosis of MM were between 30 and 54 years. Annual age-standardised mortality rates per thousand due to LC and MM in the village (age >20 years) are 7.09 and 2.48 for males, and 4.75 and 1.05 for females, respectively. Erionite fibres were found in exposed rocks and soils, which can easily become airborne and be carried into streets and recreational areas near schools and homes. Other carcinogenic elements and minerals are found only in trace amounts, except for quartz dust and asbestos (chrysotile) cement sheeting, which are also present in the neighbouring villages. CONCLUSIONS: These results indicate that environmental exposure to erionite is the main cause of the high rates of MM mortality in the Village of Tierra Blanca, supporting previous similar reports for people exposed to erionite fibres in villages in Turkey.

Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice.

BACKGROUND: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. OBJECTIVES: We performed this study to determine whether erionite evokes autoimmune reactions in mice. METHODS: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposure to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60µg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. RESULTS: Erionite and tremolite caused increased cytokine production belonging to the TH17 profile including IL-17, IL-6, TGF-ß, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. CONCLUSIONS: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities.

Environmental occurrence, origin, physical and geochemical properties, and carcinogenic potential of erionite near San Miguel de Allende, Mexico.

Detailed geologic surveys and different microscopic and analytical techniques were conducted near Tierra Blanca de Abajo where lung cancer and malignant mesothelioma (MM) are the primary causes of death. Results show that erionite-K occurs as a diagenetic product in altered Oligocene-Miocene rhyolitic tuffs. The microscopic structure of erionite minerals shows concentrations of individual fibers in the range of 0.14-0.547 µm in diameter and 2.81-50 µm in length, with a few "bundles" about 0.2-2.5 µm wide by 10-50 µm long. Chemical properties of erionite show Si/Al in the range of 3.23-3.58 (at.%) and T Si in the range of 0.76-0.78 (at.%). Potassium is the dominant cation (K > Ca > Mg > Fe). Associated minerals are heulandite, clinoptilolite, quartz, sanidine, anorthite, smectite and opal. This mineral assemblage formed in the lower part of an open catchment, where bicarbonate-rich (T > 30 °C, pH > 8) groundwater discharge conditions prevailed in the past. The physical and chemical characteristics of erionite near San Miguel de Allende are similar to those of erionite from the Cappadocian region of Turkey where erionite is associated with MM. The presence of erionite and the type of respiratory diseases that occur in the village strongly suggest the need for detailed health-based studies in the region. Pliocene-Holocene fine-grain deposits, used in the past for the construction of adobe-houses and exposed in recreational areas, also contain erionite associated with erosion and alluvial transport from the rhyolitic tuffs, potentially affecting more than 13 villages located downstream toward the Allende Dam.

Functional groups effect on the toxicity of modified ZIF-90 to Photobacterium phosphoreum.

Zeolitic imidazolate framework (ZIF) is of wide interest in biomedical applications due to its extraordinary properties such as high storage capacity, functionality and favorable biocompatibility. However, more comprehensive safety assessments are still essential before ZIF is broadly used in biomedicine. Using the characteristic that aldehyde groups on the surface of ZIF-90 can be modified with other functional groups, a series of ZIF-90s modified with different functional groups (oxime group, carboxyl group, amino group and sulfhydryl group) were synthesized to investigate the effect of functionalization on the toxicity of ZIF-90. ZIF-90 series showed concentration-dependent toxic effects on Photobacterium phosphoreum T3 and the functionalized ZIF-90s are more toxic than pristine ZIF-90, with the ZIF-90 modified with amino group (ZIF-90-NH2) showing the strongest toxicity (IC50 = 23.06 mg/L). Based on the results of the cellular assay and stability exploration, we concluded that corresponding imidazole-ligand release and the property of positively charged are responsible for the elevated toxicity of ZIF-90-NH2. Cell membrane damage, oxidative damage and luminescence damage are the main contributors to the toxic effects of ZIF-90 series. This study explored the effect of surface functionalization on the toxicity of ZIF and proposed mechanistic clues for the safety application of ZIF.

Asbestos and erionite prime and activate the NLRP3 inflammasome that stimulates autocrine cytokine release in human mesothelial cells.

BACKGROUND: Pleural fibrosis and malignant mesotheliomas (MM) occur after exposures to pathogenic fibers, yet the mechanisms initiating these diseases are unclear. RESULTS: We document priming and activation of the NLRP3 inflammasome in human mesothelial cells by asbestos and erionite that is causally related to release of IL-1ß, IL-6, IL-8, and Vascular Endothelial Growth Factor (VEGF). Transcription and release of these proteins are inhibited in vitro using Anakinra, an IL-1 receptor antagonist that reduces these cytokines in a human peritoneal MM mouse xenograft model. CONCLUSIONS: These novel data show that asbestos-induced priming and activation of the NLRP3 inflammasome triggers an autocrine feedback loop modulated via the IL-1 receptor in mesothelial cell type targeted in pleural infection, fibrosis, and carcinogenesis.

Geologic occurrences of erionite in the United States: an emerging national public health concern for respiratory disease.

Erionite, a mineral series within the zeolite group, is classified as a Group 1 known respiratory carcinogen. This designation resulted from extremely high incidences of mesothelioma discovered in three small villages from the Cappadocia region of Turkey, where the disease was linked to environmental exposures to fibrous forms of erionite. Natural deposits of erionite, including fibrous forms, have been identified in the past in the western United States. Until recently, these occurrences have generally been overlooked as a potential hazard. In the last several years, concerns have emerged regarding the potential for environmental and occupational exposures to erionite in the United States, such as erionite-bearing gravels in western North Dakota mined and used to surface unpaved roads. As a result, there has been much interest in identifying locations and geologic environments across the United States where erionite occurs naturally. A 1996 U.S. Geological Survey report describing erionite occurrences in the United States has been widely cited as a compilation of all US erionite deposits; however, this compilation only focused on one of several geologic environments in which erionite can form. Also, new occurrences of erionite have been identified in recent years. Using a detailed literature survey, this paper updates and expands the erionite occurrences database, provided in a supplemental file (US_erionite.xls). Epidemiology, public health, and natural hazard studies can incorporate this information on known erionite occurrences and their characteristics. By recognizing that only specific geologic settings and formations are hosts to erionite, this knowledge can be used in developing management plans designed to protect the public.

Low-dose of zeolitic imidazolate framework-8 nanoparticle cause energy metabolism disorder through lysosome-mitochondria dysfunction.

Understanding the underlying interaction between nanoparticle and organelles is conclusive to the nanotoxicology. According to existing literatures, lysosome is a crucial target of the nanoparticle carrier. Meanwhile, mitochondria could provide the essential energy for nanopaticles entering/exiting the cell. Based on the investigation of lysosome-mitochondria connection, we decoded the effects of low-dose ZIF-8 on energy metabolism, which are still largely obscure beforehand. In this research, low-dose ZIF-8 NPs were utilized to explore the effects on vascular endothelial cells, the first cells exposed to NPs during intravenous injection. Consequently, ZIF-8 could damage the energy metabolism, mainly manifested as mitochondrial fission, the decreased ATP production, and lysosomal dysfuction, which would subsequently affect the cell survival, proliferation and protein expression. This study highlights the fundamental understanding for exploring the regulation of nanoscale ZIF-8 in biological processes and its further application in biomedical field.

SOD mineralized zeolitic imidazole framework-8 for the treatment of chemotherapy-related acute kidney injury.

Acute kidney injury (AKI), a prevalent and fatal adverse event, seriously affects cancer patients undergoing chemotherapy. The most important pathological mechanism of AKI is oxidative stress from reactive oxygen species (ROS). Currently, ROS scavenging is a promising strategy to manage the risk of chemotherapy-induced AKI. Herein, we successfully synthesized SOD@ZIF-8 nanoparticles by biomimetic mineralization, which were taken up by cells and could improve cell viability by limiting oxidative stress damage, as found in in vitro studies. Moreover, SOD@ZIF-8 nanoparticles exhibit broad-spectrum antioxidant properties in addition to significant renal accumulation in AKI mice, preventing clinically related cisplatin-induced AKI in murine models. AKI alleviation in the model was validated by measuring blood serum, staining kidney tissue, and related biomarkers. SOD@ZIF-8 nanoparticle therapeutic efficiency exceeds NAC, a small molecular antioxidant functioning through free radical scavenging. The results suggest SOD@ZIF-8 nanoparticles as a potential therapeutic option for AKI and other ROS-related disorders.

Environmental decomposition and remodeled phytotoxicity of framework-based nanomaterials.

Zeolitic imidazole frameworks (ZIFs) have attracted a considerable amount of attention for use in environmental applications (e.g., pollutant adsorption and photocatalysis in water treatments). The environmental stability and toxicity of ZIFs are key prerequisites for their practical applications, but information about these factors is largely lacking. The present work finds that pristine ZIFs (ZIF-8 and ZIF-67) photodegrade from frame structures into two-dimensional nanosheets and are oxidized to zinc carbonate (ZIF-8) and Co3O4 (ZIF-67) under visible-light irradiation. The photoinduced electrons, holes and free radicals promote dissolution of the metal cores and organic ligands, leading to collapse of the frame structure. The photodegradation of ZIF-8 alleviates developmental inhibition, oxidative stress, plasmolysis, and photosynthetic toxicity, while the photodegradation of ZIF-67 aggravates nanotoxicity. The integration of metabolomics and transcriptomics analysis reveals that unsaturated fatty acid biosynthesis and metal ion-binding transcription contribute to the altered toxicity of ZIF photodegradation. These findings highlight the roles of photodegradation in structural transformation and alteration of the toxicity of ZIFs, alarming the study of pristine metal-organic frameworks (MOFs).

Nano-sized zeolite-like metal-organic frameworks induced hematological effects on red blood cell.

Understanding the toxicity of metal-organic frameworks (MOFs) is important for improving their biocompatibility in further applications, especially the hematotoxicity of MOFs due to the unavoidable contact of MOFs with blood in biomedical science. Here we report the hematotoxicity and underlying mechanisms of nano-sized zeolite-like MOFs ZIF-8 and ZIF-67 because of their wide applications in biomedical science. ZIF-67 induced significant hemolysis of red blood cell (Rb) through breaking the structure of membrane due to the generation of free radicals, whereas ZIF-8 was hematocompatible. ZIF-67 was thus internalized by Rb and then bound with hemoglobin via hydrogen bond and van der Waals force, which influenced the structure and function of hemoglobin in accompany with heme release. These findings reveal the detailed mechanism of the hematological effects of MOFs on Rb and are helpful to the assessment of the toxicity and potential health risks of MOFs and the design of biosafe MOFs for biomedical applications.