共查询到20条相似文献,搜索用时 671 毫秒
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Yuka Suzuki Saeko Tada-Oikawa Gaku Ichihara Masayuki Yabata Kiyora Izuoka Masako Suzuki Kiyoshi Sakai Sahoko Ichihara 《Toxicology and applied pharmacology》2014
Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO2 and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO2 particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation. 相似文献
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Chen-Chen Lee Shih-Hsuan Huang Ya-Ting Yang Yu-Wen Cheng Ching-Hao Li Jaw-Jou Kang 《Toxicology in vitro》2012,26(4):552-560
Epidemiological studies have shown that there is a strong correlation between atherosclerosis and ambient air pollution. In this study, we found that motorcycle exhaust particles (MEP) induced adhesion between cells of the human monocytic leukemia cell line (THP-1) and human umbilical vein endothelial cells (HUVECs) in a time-and dose-dependent manner. In addition, MEP treatment induced both mRNA and protein expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HUVECs. The IκB degradation and p65 nuclear translocation was found in MEP-treated HUVECs, suggested the involvement of nuclear factor-κB (NF-κB). MEP-induced VCAM-1 and ICAM-1 protein expression was inhibited by NF-κB inhibitor BAY 11-7085. Oxidative stress was also involved in the signaling of VCAM-1 and ICAM-1 expression. MEP treatment caused hydrogen peroxide and superoxide formation. Pretreatment with α-tocopherol could inhibit MEP-induced reactive oxygen intermediates generation and suppressed MEP-induced IκB degradation and adhesion molecules expression. Furthermore, the carbon black (CB) nanoparticles with different diameters could induce VCAM-1 and ICAM-1 protein expression; however, polycyclic aromatic hydrocarbons (PAHs) only increased the expression of ICAM-1 but not that of VCAM-1 in HUVECs. In this study, we found that MEPs could induce ICAM-1 and VCAM-1 expression through oxidative stress and NF-κB activation in HUVECs. 相似文献
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Yuxiu Gu Shanshan Cheng Gui Chen Yuexin Shen Xiyue Li Qin Jiang 《Toxicology mechanisms and methods》2017,27(3):191-200
It was recently shown that ZnO nanoparticles (NPs) could induce endoplasmic reticulum (ER) stress in human umbilical vein endothelial cells (HUVECs). If ER stress is associated the toxicity of ZnO NPs, the presence of ER stress inducer thapsigargin (TG) should alter the response of HUVECs to ZnO NP exposure. In this study, we addressed this issue by assessing cytotoxicity, oxidative stress and inflammatory responses in ZnO NP exposed HUVECs with or without the presence of TG. Moreover, TiO2 NPs were used to compare the effects. Exposure to 32?μg/mL ZnO NPs (p?0.05), but not TiO2 NPs (p?>?0.05), significantly induced cytotoxicity as assessed by WST-1 and neutral red uptake assay, as well as intracellular ROS. ZnO NPs dose-dependently increased the accumulation of intracellular Zn ions, and ZnSO4 induced similar cytotoxic effects as ZnO NPs, which indicated a role of Zn ions. The release of inflammatory proteins tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) or the adhesion of THP-1 monocytes to HUVECs was not significantly affected by ZnO or TiO2 NP exposure (p?>?0.05). The presence of 250?nM TG significantly induced cytotoxicity, release of IL-6 and THP-1 monocyte adhesion (p?0.01), but did not significantly affect intracellular ROS or release of TNFα (p?>?0.05). ANOVA analysis indicated no interaction between exposure to ZnO NPs and the presence of TG on almost all the endpoints (p?>?0.05) except neutral red uptake assay (p?0.01). We concluded ER stress is probably not associated with ZnO NP exposure induced oxidative stress and inflammatory responses in HUVECs. 相似文献
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Kwon OE Lee HS Lee SW Chung MY Bae KH Rho MC Kim YK 《Archives of pharmacal research》2005,28(1):55-60
Leukocyte adhesion to the vascular endothelium is a critical initiating step in inflammation and atherosclerosis. We have herein studied the effect of manassantin A (1) and B (2), dineolignans, on interaction of THP-1 monocytic cells and human umbilical vein endothelial cells (HUVEC) and expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in HUVEC. When HUVEC were pretreated with 1 and 2 followed by stimulation with TNF-alpha, adhesion of THP-1 cells to HUVEC decreased in dose-dependent manner with IC50 values of 5 ng/mL and 7 ng/mL, respectively, without cytotoxicity. Also, 1 and 2 inhibited TNF-alpha-induced up-regulation of ICAM-1, VCAM-1 and E-selectin. The present findings suggest that 1 and 2 prevent monocyte adhesion to HUVEC through the inhibition of ICAM-1, VCAM-1 and E-selectin expression stimulated by TNF-alpha, and may imply their usefulness for the prevention of atherosclerosis relevant to endothelial activation. 相似文献
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Ali Kermanizadeh Kim Jantzen Michael B. Ward Jon Ambæk Durhuus Lene Juel Rasmussen Steffen Loft 《Nanotoxicology》2017,11(2):184-200
Autophagy is the catabolic process involving the sequestration of the cytoplasm within double-membrane vesicles, which fuse with lysosomes to form autolysosomes in which autophagic targets are degraded. Since most endocytic routes of nanomaterial uptake converge upon the lysosome and the possibility that autophagy induction by NMs may be an attempt by the cell to self-preserve following the external challenge, this study investigated the role of autophagy following exposure to a panel of widely used metal-based NMs with high toxicity (Ag and ZnO) or low toxicity (TiO2) in a pulmonary (A549) and hepatic (HepG2) cell line. The in vitro exposure to the Ag and ZnO NMs resulted in the induction of both apoptosis and autophagy pathways in both cell types. However, the progression of autophagy was blocked in the formation of the autolysosome, which coincided with morphologic changes in the actin cytoskeleton. This response was not observed following the exposure to low-toxicity TiO2 NMs. Overall, the results show that high toxicity NMs can cause a dysfunction in the autophagy pathway which is associated with apoptotic cell death. 相似文献
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Inhibitory activity of lignan components from the flower buds of Magnoliae fargesii on the expression of cell adhesion molecules 总被引:2,自引:0,他引:2
Inhibitory activity of lignans isolated from Magnoliae fargesii Cheng on cell adhesion molecules on the surface of THP-1 human monocytic cell lines were investigated. Among 16 lignan components tested, six displayed relatively potent inhibitory activity on the expression of both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). 相似文献
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María del Pilar Ramos-Godínez Blanca Eunice González-Gómez Angélica Montiel-Dávalos Rebeca López-Marure Ernesto Alfaro-Moreno 《Toxicology in vitro》2013,27(2):774-781
The effects of particulate matter (PM) on endothelial cells have been evaluated in vitro by exposing isolated endothelial cells to different types of PM. Although some of the findings from these experiments have been corroborated by in vivo studies, an in vitro model that assesses the interaction among different cell types is necessary to achieve more realistic assays. We developed an in vitro model that mimics the alveolar–capillary interface, and we challenged the model using TiO2 nanoparticles (TiO2-NPs). Human umbilical endothelial cells (HUVECs) were cultured on the basolateral side of a membrane and pneumocytes (A549) on the apical side. Confluent co-cultures were exposed on the apical side to 10 μg/cm2 of TiO2-NPs or 10 ng/mL of TNFα for 24 h. Unexposed cultures were used as negative controls. We evaluated monocyte adhesion to HUVECs, adhesion molecule expression, nitric oxide concentration and proinflammatory cytokine release. The TiO2-NPs added to the pneumocytes induced a 3- to 4-fold increase in monocyte adhesion to the HUVECs and significant increases in the expression of adhesion molecules (4-fold for P-selectin at 8 h, and about 8- and 10-fold for E-selectin, ICAM-1, VCAM-1 and PECAM-1 at 24 h). Nitric oxide production also increased significantly (2-fold). These results indicate that exposing pneumocytes to TiO2-NPs causes endothelial cell activation. 相似文献
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Inhibitory activity of stilbenes from medicinal plants on the expression of cell adhesion molecules on THP1 cells 总被引:2,自引:0,他引:2
The inhibitory activity of stilbenes isolated from medicinal plants on cell adhesion molecules on the surface of THP-1 human monocytic cell lines was investigated. Among ten stilbenes tested, four stilbenes displayed a significant inhibitory activity on the expression of both intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). A cell-to-cell adhesion assay showed that 3,5-dihydroxy-4'-methoxystilbene and 2,3,4',5-tetrahydroxystilbene-2-O-beta-D-glucopyranoside as well as resveratrol blocked significantly TNF-alpha-inducing cell-cell adhesion between human umbilical vein endothelial cells (HUVEC) and THP-1 cells. 相似文献
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Ursula G. Sauer Sandra Vogel Alexandra Aumann Annemarie Hess Susanne N. Kolle Lan Ma-Hock Wendel Wohlleben Martina Dammann Volker Strauss Silke Treumann Sibylle Gröters Karin Wiench Bennard van Ravenzwaay Robert Landsiedel 《Toxicology and applied pharmacology》2014
The applicability of rat precision-cut lung slices (PCLuS) in detecting nanomaterial (NM) toxicity to the respiratory tract was investigated evaluating sixteen OECD reference NMs (TiO2, ZnO, CeO2, SiO2, Ag, multi-walled carbon nanotubes (MWCNTs)). Upon 24-hour test substance exposure, the PCLuS system was able to detect early events of NM toxicity: total protein, reduction in mitochondrial activity, caspase-3/-7 activation, glutathione depletion/increase, cytokine induction, and histopathological evaluation. Ion shedding NMS (ZnO and Ag) induced severe tissue destruction detected by the loss of total protein. Two anatase TiO2 NMs, CeO2 NMs, and two MWCNT caused significant (determined by trend analysis) cytotoxicity in the WST-1 assay. At non-cytotoxic concentrations, different TiO2 NMs and one MWCNT increased GSH levels, presumably a defense response to reactive oxygen species, and these substances further induced a variety of cytokines. One of the SiO2 NMs increased caspase-3/-7 activities at non-cytotoxic levels, and one rutile TiO2 only induced cytokines. Investigating these effects is, however, not sufficient to predict apical effects found in vivo. Reproducibility of test substance measurements was not fully satisfactory, especially in the GSH and cytokine assays. Effects were frequently observed in negative controls pointing to tissue slice vulnerability even though prepared and handled with utmost care. Comparisons of the effects observed in the PCLuS to in vivo effects reveal some concordances for the metal oxide NMs, but less so for the MWCNT. The highest effective dosages, however, exceeded those reported for rat short-term inhalation studies. To become applicable for NM testing, the PCLuS system requires test protocol optimization. 相似文献
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目的:探讨阿托伐他汀对内皮细胞微粒(EMPs)诱导的人脐静脉内皮细胞(HUVECs)表达血管细胞粘附分子(VCAM)-1和细胞间粘附分子(ICAM)-1的影响。方法:取生长良好的第4,5代人脐静脉内皮细胞,将细胞分为3大组:对照组、EMPs组、EMPs+阿托伐他汀组。对照组加入培养基,EMPs组以不同浓度的EMPs(0/mL,1×102/mL,1×103/mL,1×104/mL,1×105/mL)与HUVECs共同孵育24 h,EMPs+阿托伐他汀组以不同浓度的阿托伐他汀(0.05,0.1,1.0,10μmol.L-1)与HUVECs作用1 h后,加入105/mL EMPs共同孵育24 h。分别采用实时荧光定量聚合酶链反应和蛋白免疫印迹方法检测VCAM-1和ICAM-1 mRNA和蛋白的表达。结果:HUVECs受EMPs刺激后,VCAM-1和ICAM-1 mRNA及蛋白表达呈浓度依赖性增加,阿托伐他汀可不同程度上抑制EMPs的作用。结论:阿托伐他汀抗动脉粥样硬化作用可能部分与抑制EMPs诱导的内皮细胞VCAM-1和ICAM-1的表达有关。 相似文献
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Yu-ping Zhu Tao Shen Ya-jun Lin Bei-dong Chen Yang Ruan Yuan Cao Yue Qiao Yong Man Shu Wang Jian Li 《Acta pharmacologica Sinica》2013,34(8):1036-1042
Aim:
To investigate the effects Astragalus polysaccharides (APS) on tumor necrosis factor (TNF)-α-induced inflammatory reactions in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanisms.Methods:
HUVECs were treated with TNF-α for 24 h. The amounts of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were determined with Western blotting. HUVEC viability and apoptosis were detected using cell viability assay and Hoechst staining, respectively. Reactive oxygen species (ROS) production was measured by DHE staining. Monocyte and HUVEC adhesion assay was used to detect endothelial cell adhesive function. NF-κB activation was detected with immunofluorescence.Results:
TNF-α (1-80 ng/mL) caused dose- and time-dependent increases of ICAM-1 and VCAM-1 expression in HUVECs, accompanied by significant augmentation of IκB phosphorylation and NF-κB translocation into the nuclei. Pretreatment with APS (10 and 50 μg/mL) significantly attenuated TNFα-induced upregulation of ICAM-1 VCAM-1 and NF-κB translocation. Moreover, APS significantly reduced apoptosis, ROS generation and adhesion function damage in TNF-α-treated HUVECs.Conclusion:
APS suppresses TNFα-induced adhesion molecule expression by blocking NF-κB signaling and inhibiting ROS generation in HUVECs. The results suggest that APS may be used to treat and prevent endothelial cell injury-related diseases. 相似文献14.
We investigated whether ginsenoside Rb1 (Rb1) could block tumor necrosis factor-alpha (TNF-alpha)-induced over-expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and human lung microvascular endothelial cells (HMVECs-L). Cells were treated with various concentrations of TNF-alpha with or without Rb1 pre-treatment for 16 h. The mRNA and protein levels of VCAM-1 were determined with real-time polymerase chain reaction (PCR) and flow cytometry, respectively. Human monocytic THP-1 cells labeled with fluorescent dye (Calcein-AM) was used for the adhesion assay on HUVEC monolayers. Dihydroethidium (DHE) was used to demonstrate in situ levels of superoxide production. JC-1 dye was used to measure changes in mitochondrial membrane potential. Activation of mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) was determined by Bio-Plex immunoassay. TNF-alpha treatment significantly increased the mRNA and protein levels of VCAM-1 in HUVECs in a dose dependent manner. Rb1 pre-treatment effectively blocked the TNF-alpha-induced expression of VCAM-1 mRNA or protein by 80% and 43%, respectively (p<0.01). THP-1 adhesion was also blocked. Furthermore, Rb1 reduced the TNF-alpha-induced increase of superoxide anion production by 41% and inhibited the TNF-alpha-induced decrease of mitochondrial membrane potential by 44% in HUVECs. Rb1 also effectively blocked TNF-alpha-induced activation of p38, c-Jun N-terminal protein kinase, extracellular signal-regulated kinase 1/2 and IkappaBalpha. In conclusion, Rb1 effectively blocked the TNF-alpha-induced over-expression of VCAM-1, increased THP-1 adhesion and over-production of superoxide anion. Furthermore, Rb1 inhibited TNF-alpha-induced MAPKs and NF-kappaB activation. These data suggested that Rb1 might have potential therapeutic effects in controlling inflammation in vascular diseases. 相似文献
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Forchhammer L Loft S Roursgaard M Cao Y Riddervold IS Sigsgaard T Møller P 《Toxicology letters》2012,209(2):121-128
Toxicological effects of wood smoke particles are less investigated than traffic-related combustion particles. We investigated the effect of wood smoke particles, generated by smouldering combustion conditions, on human umbilical endothelial cells (HUVECs) co-cultured with or without monocytic THP-1 cells. Standard reference material (SRM) 2975 diesel exhaust particles were used as benchmark particles. Wood smoke particles at 50 μg/ml or 100 μg/ml caused adhesion of THP-1 monocytes onto HUVECs in co-cultures, whereas SRM2975 had no such effect. Both types of particles from 1 μg/ml increased VCAM-1 expression on HUVECs in mono-cultures. However, only the exposure to wood smoke particles was associated with increased expression of TNF and IL8 mRNA in THP-1 cells. We found no effect on the intracellular production of reactive oxygen species by the fluorescent probe DCFH-DA, whereas especially the wood smoke particles caused increased level of DNA strand breaks and oxidised guanines at concentrations with low cytotoxicity. In conclusion, our results indicate that the adherence of monocytes on endothelial cells in wood smoke particle exposed cultures depend on activation of both cell types. 相似文献
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白黎芦醇对fMLP诱导中性白细胞与人脐静脉内皮细胞粘附的抑制作用及机制 总被引:1,自引:3,他引:1
目的研究白藜芦醇(resveratrol,Res)对趋化肽N-甲酰-甲硫氨酰-亮氨酰苯丙氨酸(fMLP)诱导中性白细胞与人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)的粘附及HUVECs释放可溶性粘附分子的影响。方法观察不同浓度Res对fMLP(10μmol.L-1)刺激HU-VECs与中性白细胞粘附的影响。以ELISA法测定可溶性细胞间粘附分子,血管细胞粘附分子和E-选择素。以Fura-3和海萤萤光素诱导剂为荧光指示剂分别测定中性白细胞内[Ca2+]i水平和O2.浓度。结果Res(1~50μmol.L-1)明显抑制fMLP诱导的中性白细胞与HUVECs的粘附反应,同时,明显抑制fMLP诱导粘附分子的释放效应。Res抑制中性白细胞中O2.生成和[Ca2+]i升高,其中Res5μmol.L-1和50μmol.L-1与fMLP诱导组相比具有统计学意义(P<0.01)。结论白藜芦醇通过影响中性白细胞内O2.生成和[Ca2+]i水平,抑制中性白细胞与内皮细胞的粘附以及细胞间粘附分子表达,在阻断炎性反应的发生与发展过程中发挥着重要作用。 相似文献
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目的探讨s-油酰丙醇胺对用肿瘤坏死因子α(TNF-α)诱导的人脐静脉内皮细胞黏附分子(VCAM-1,I-CAM-1,E选择素)表达的影响。方法从新鲜的脐带中分离出人脐静脉内皮细胞,培养至3~9代,用不同浓度的s-油酰丙醇胺(10,50,100μmol/L)孵育12 h后,用TNF-α(20 ng/mL)孵育8 h,采用荧光实时定量PCR和细胞酶联免疫吸附试验分别检测VCAM-1,ICAM-1,E选择素的mRNA及蛋白的表达,同时采用细胞黏附实验检测其对细胞黏附的影响。结果相对于正常的人脐静脉内皮细胞,TNF-α诱导后的人脐静脉内皮细胞黏附分子(VCAM-1,ICAM-1,E-选择素)的表达明显增加。s-油酰丙醇胺可以显著的抑制VCAM-1的表达,并呈现出一定的剂量依赖性,而且对人急性单核细胞性白血病细胞(THP-1)的黏附也有明显的抑制作用,但对ICAM-1,E-选择素的表达却没有影响。结论s-油酰丙醇胺和大多数的PPARα激动剂一样,能够抑制慢性炎症,减少单核细胞的黏附,抑制VCAM-1的表达,而对急性炎症没有作用,如对E-选择素的表达无影响。 相似文献
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槲皮素对TNFα诱导的内皮细胞与中性粒细胞粘附的抑制作用 总被引:10,自引:0,他引:10
目的:研究槲皮素对TNFα诱导的内皮细胞与中性粒细胞粘附的抑制作用及作用机制。方法:用髓过氧化酶法测定中性粒细胞与内皮细胞的粘附,ELISA法测定内皮细胞粘附分子的表达。结果:TNFα通过增加/诱导内皮细胞ICAM-1,VCAM-1及E-selectin的表达而剂量、时间依赖性地增加内皮细胞与中性粒细胞的粘附。槲皮素可剂量依赖性地抑制上述粘附,其作用机制为抑制TNFα诱导内皮细胞上述3种粘附分子的表达。结论:槲皮素通过抑制ICAM-1,VCAM-1及E-selectin的表达而降低TNFα诱导的内皮细胞与中性粒细胞的粘附。 相似文献
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Olesja M. Bondarenko Margit Heinlaan Mariliis Sihtmäe Angela Ivask Imbi Kurvet Elise Joonas 《Nanotoxicology》2016,10(9):1229-1242
Within EU FP7 project NANOVALID, the (eco)toxicity of 7 well-characterized engineered nanomaterials (NMs) was evaluated by 15 bioassays in 4 laboratories. The highest tested nominal concentration of NMs was 100?mg/l. The panel of the bioassays yielded the following toxicity order: Ag?>?ZnO?>?CuO?>?TiO2?>?MWCNTs?>?SiO2?>?Au. Ag, ZnO and CuO proved very toxic in the majority of assays, assumingly due to dissolution. The latter was supported by the parallel analysis of the toxicity of respective soluble metal salts. The most sensitive tests/species were Daphnia magna (towards Ag NMs, 24-h EC50?=?0.003?mg Ag/l), algae Raphidocelis subcapitata (ZnO and CuO, 72-h EC50?=?0.14?mg Zn/l and 0.7?mg Cu/l, respectively) and murine fibroblasts BALB/3T3 (CuO, 48-h EC50?=?0.7?mg Cu/l). MWCNTs showed toxicity only towards rat alveolar macrophages (EC50?=?15.3?mg/l) assumingly due to high aspect ratio and TiO2 towards R. subcapitata (EC50?=?6.8?mg Ti/l) due to agglomeration of TiO2 and entrapment of algal cells. Finally, we constructed a decision tree to select the bioassays for hazard ranking of NMs. For NM testing, we recommend a multitrophic suite of 4 in vitro (eco)toxicity assays: 48-h D. magna immobilization (OECD202), 72-h R. subcapitata growth inhibition (OECD201), 30-min Vibrio fischeri bioluminescence inhibition (ISO2010) and 48-h murine fibroblast BALB/3T3 neutral red uptake in vitro (OECD129) representing crustaceans, algae, bacteria and mammalian cells, respectively. Notably, our results showed that these assays, standardized for toxicity evaluation of “regular” chemicals, proved efficient also for shortlisting of hazardous NMs. Additional assays are recommended for immunotoxicity evaluation of high aspect ratio NMs (such as MWCNTs). 相似文献