From: Cellular Toxicity and Immunological Effects of Carbon-based Nanomaterials
Test materials | Exposure pathways | Exposure doses | Suspension buffer | Time points of sacrifice | Test animals | Main findings | Refe-rence |
---|---|---|---|---|---|---|---|
MWCNTs | Pharyngeal aspiration | 40 μg/mouse | PBS with 0.6 mg/mL serum albumin and 0.01 mg/mL 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DSPC) | 24 h, 7 days, and 28 days | C57BL/6 mice aged 10 weeks | An early increase in serum cytokines and inflammatory gene expression in serum; consistently increased eosinophils in blood and BALF. | [34] |
Biodegraded and non-biodegraded carbon nanotubes | Pharyngeal aspiration | 40 μg/mouse | PBS for non-biodegraded CNTs; PBS with hMPO and H2O2 for biodegrated CNTs | 7 days | C57BL/6 mice | No pro-inflammatory pulmonary response observed in mice treated with biodegraded nanotubes. | [73] |
Carbon black nanoparticles | Intratracheal instillation (single) | 0.018, 0.054 or 0.162 mg/mouse | 0.9% NaCl MilliQ water with 10% (v/v) acellular BAL from C57BL/6 mice. | 1, 3 and 28 days | Female C57BL/6 mice aged 5-6 weeks | Strongest lung inflammation on day 1 and day 3 post exposure, elevating for the two highest doses (0.054 and 0.162 mg) 28 days post-exposure. | [114] |
High-purity WMCNTs | Orotracheal aspiration | 4 mg/kg body weight | PBS with 1% Pluronic F127 | 1 h, 6 h, 12 h, 18 h, 24 h, 48 h and 72 h | CF-1 Non-Swiss Albino mice aged 6 weeks | Time-dependent neutrophil influx and pro-inflammatory mediator (TNF-α and IL-6) release in bronchoalveolar lavage (BAL) fluid; attenuated influx of neutrophils in AM-depleted mice. | [115] |
MWCNTs | Intratracheal instillation; inhalation | 0.2 mg or 1 mg/mouse; 0.37mg/m3 aerosols (6 h/day, 5 days/week) for 4 weeks | Distilled water with 0.05% Triton X | 3 days, 1 week, 1 month, 3 months, and 6 months; 3 days, 1 month, and 3 months | Male Wistar rats aged 9 weeks | Less amounts of MWCNTs delivered into the lungs, and therefore less pulmonary inflammation responses in the group of inhalation exposure compared to intratracheal instillation. | [116] |
SWCNTs | Intratracheal instillation | 0.04, 0.2, 1 mg/kg body weight | PBS with 10 mg/mL Tween 80 | 3 days, 1 week, 1 month, 3 months and 6 months | Male Crl: CD (SD) rats aged seven weeks | Increased inflammatory cells in BALF in a dose-dependent manner from 3 days post-exposure up to 3 months; alveolar macrophage accumulation and inflammatory cell infiltration in the lung sections. | [117] |
Long tangled MWCNTs and long rod-like MWCNTs | Pharyngeal aspiration | 10 or 40 μg/mouse | PBS with 0.6 mg/ml BSA | 4 and 16 h or 7, 14, and 28 days | Female C57BL/6 mice aged 7–8 weeks | Attenuated inflammatory reactions caused by CNTs in IL-1R-/-mice and antagonist-treated (etanercept and anakinra) mice | [119] |
MWCNTs | Pharyngeal aspiration | 5, 20, or 40 μg/mouse | Ca2+ and Mg2+-free PBS with 0.6 mg/ml mouse serum albumin and 0.01 mg/ml DPPC | 1, 3, 7 and 14 days | Male C57BL/6J mice aged 8 weeks | Rapid and prominent fibrosis formation remarkably near where the particles were deposited in the lungs; pronounced infiltration of neutrophils and macrophages alongside fibrosis. | [122] |
SWCNTs and fullerenes | Intratracheal instillation | Low dose: 0.0003, 0.0015, 0.003, 0.015, and 0.3 mg/mouse; high dose: 0.1 and 0.5 mg/mouse | Pluronic F-68 | 7 days | Male ICR mice aged 5-6 weeks | Airway hyperreactivity and airflow obstruction; upregulation of cathepsin K, MMP-12, CCL2 and CCL3, and macrophage receptors such as Toll-like receptor 2 and macrophage scavenger receptor 1. | [123] |
SWCNTs, MWCNTs and ultrafine carbon black particles | Subcutaneous injection into the footpad together with OVA; intranasal administration together with OVA. | For the injection model, ~200 μg /single dose (max dose with fourfold dilutions) for 3 doses; for the intranasal model, 133 μg/day for 3consecutive days | Hank’s balanced salt solution with 10% serum from BALB/cA mouse | An OVA booster on days 21, sacrificed on days 26; An OVA booster on days 21,22 and 23, sacrificed on days 26. | Female inbred BALB/cAnNCrl mice aged 6–7 weeks | Increased serum levels of OVA-specific IgE, number of eosinophils in BALF, and secretion of Th2-associated cytokines in the mediastinal lymph node in the group of CNTs together with OVA; increased IgG2a levels, neutrophil cell numbers, and levels of TNF-α and MCP-1 in BALF in the group of MWCNT and ufCB with OVA. | [124] |
MWCNTs | Intratracheal instillation | 50 μg/mouse once a week for 6 weeks | PBS with 0.05% Tween 80 | 24 h after the final intratracheal administration | Male ICR mice aged 6-7 weeks | Aggravated airway inflammation observed in the group of OVA+MWCNTs, characterized by infiltration of immune cells and production of cytokines; increased levels of serum immunoglobulin (allergen-specific IgG1 and IgE) compared with OVA alone. | [125] |
Carbon nanoparticles | Pharyngeal aspiration | 2.5 mg/kg body weight | PBS | 12 h, 24 h, 48 h | Female Balb/cJRj mice aged 8 weeks | Increased allergic airway inflammation and specific Th2 response in the lymph nodes to OVA in the presence of carbon nanoparticles. | [126] |
Carbon nanoparticles | Intratracheal instillation | 20 μg/mouse | Pyrogene-free distilled water | 3, 6, 12, 18, 24 h, and 3 or 7 days | Female C57BL/6 J mice aged 8–10 weeks | Prominent culmination of neutrophil granulocytes 12 to 24 h after instillation; BAL concentrations and increased levels of neutrophil chemoattractants (CXCL1, -2 and-5) from alveolar epithelial type II cells. | [127] |
MWCNTs | Intranasal instillation | administered on days 0, 7, and 14 (75 μg/dose) | A synthetic lung surfactant | On the day 23 | Male BALB/cByJ mice aged 9 weeks | Aggravated airway inflammation and the generation of epithelium-derived innate cytokines caused by the coexposure of MWCNTs and HDM compared to HDM alone. | [128] |
Rod-like MWCNTs and tangled MWCNTs | Inhalation | 6.2-8.2 mg/m3 for rCNT and 17.5-18.5 mg/m3 for tCNT (4 hours at a time once or on four consecutive days) | — | 4 h, 24 h | Female C57BL/6 and BALB/c mice aged 7–8 weeks | Allergic-like airway inflammation and the upregulation of innate immunity-relevant genes and cytokine/chemokine pathways caused by rod-like CNTs after 4-hour exposure. | [129] |
MWCNTs | Oropharyngeal aspiration | 4 mg/kg body weight | Saline with 10% surfactant | 1 or 30 days | C57BL/6J and B6.Cg-kit (W-sh) mast cell deficient mice aged 4–10 weeks | Involvement of mast cells and the IL-33/ST2 axis in the pulmonary and cardiovascular responses to MWCNT exposure; no toxicological effects observed in mast cell-deficient mice or in mice without response to IL-33. | [132] |
MWCNTs | Intratracheal instillation | 5, 20, and 50 mg/kg body weight | PBS | 1,3, 7,14 days | Male ICR mice | Increased pro-inflammatory cytokines in BALF and in blood in a dose-dependent manner, peaking at day 1 postexposure; more pronounced elevation of Th2-type cytokines than that of Th1-type cytokines; considerably enhanced number of B cells in the spleen and blood. | [133] |
MWCNTs | Intravenous injection | 100 μg/mouse | Ca2+ and Mg2+-free PBS | 24 h, 7 days and 15 days | Female C57BL/6 mice aged 6-8 weeks | Proliferative response of T lymphocytes to a nonspecific mitogen and to ovalbumin (OVA); an increase in expression of proinflammatory cytokines such as TNF-α and IL-6 and IFN-γ, and a decrease in TGF-β and IL-10; increased antibody production to OVA in the treated group. | [134] |
nonPEGylated SWCNTs | Intravenous injection | 1.2 mg/kg body weight | PBS | 6 min and 60 min | Male Wistar rats of body weight 250–280 g | A significant rise in plasma thromboxane B2 levels. | [145] |
MWCNTs | Inhalation | 0.3, 1, or 5 mg/m3 (6 h/day) for 7 or 14 days | — | 7 or 14 days | Male C57BL/6 mice aged 10 weeks | An absence of severe inflammation and tissue injury; decreased NK cell function and T cell-dependent antibody response. | [148] |
MWCNTs | Inhalation | 0, 0.3 or 1 mg/m3 (6 h/day) for 14 consecutive days | — | — | Male C57Bl/6 mice aged approximately 8 weeks | A dose-dependent decrease in antibody formation in response to antigen, not altering lymphocyte subpopulations; activation of the cyclooxygenase pathway in the spleen by MWCNTs through TGF-ß release in the lung, leading to T-cell dysfunction and decreased T-cell-dependent antibody formation. | [149] |
MWCNTs | Pharyngeal aspiration | 50 μg/mouse | PBS with 0.6 mg/ml mouse serum albumin and 0.01 mg/ml DPPC | day 7, 28 | Wild-type C57BL/6 and IL-1R-/- mice aged 2 months | Severe acute pulmonary inflammation, and increases of TNF-α, IL-6, IL-1β and MCP-1 protein levels in BALF in wild-type mice; reduced pulmonary inflammatory response in IL-1R-/- mice exposed to MWCNT. | [157] |
Four samples of MWCNTs: NTtang1 (diameter ~14.84 nm, length 1-5 μm), NTtang2 (diameter ~10.40 nm, length 5-20 μm), NTlong1 (diameter ~84.89 nm, mean length 13 μm) and NTlong2 (diameter ~165.02 nm, max length 56 μm) | Intraperitoneal injection | 50 μg/mouse | Saline with 0.5% BSA | 24 h and 7 days | Female C57BL/6 mice aged 8 weeks | Significant polymorphonuclear leukocyte (PMN) or protein exudation and granulomas formation on the peritoneal side of the diaphragm in the group of long-fiber-containing samples. | [160] |
Nano-sized carbon black | Inhalation | For a 3-day experiment, 13.08 ± 3.18 mg/m3 of non-sonicated carbon black (group N) and 13.67 ± 3.54 mg/m3 of sonicated carbon black (group S); for a 2-week experiment, 9.83 ±3.42 mg/m3 of non-sonicated carbon black and 9.08 ± 4.49 mg/m3 of sonicated carbon black. (exposed 6 h/day, 5 days/week for 3 days or 2 weeks) | Distilled water | — | Male Sprague-Dawley (SD) rats aged 5 weeks | More carbon black particles-laden macrophages observed in BALF and more carbon black deposited in the lungs exposed to sonicated carbon black; no significant difference in the levels of inflammatory cytokines or damage-indicating proteins between the two groups in the 3-day experiment, whereas 2-week exposure induced increased number of total cells, macrophages, and PMNs in the group S. | [163] |
SWCNTs, MWCNTs (diameter 10-15 nm), MWCNTs (diameter 20-50 nm) and MWCNTs (diameter 3-10 nm) | Intratracheal instillation | 100 mg/rat | NaCl solution with or without 0.5 mg/ml BSA | 24 h | Male Sprague Dawley rats of body weight 180-220 g | Remarkably accentuated inflammatory cell infiltration in BALF, and increased the number of CNT-loaded alveolar macrophages, caused by CNTs dispersed in BSA, but not in NaCl solution, indicating the potential importance of CNT dispersion for the toxicological studies. | [164] |
Several types of covalently functionalized MWCNTs: COOH-MWCNTs, sw-NH2- MWCNTs, NH2-MWCNTs, PEG-MWCNTs and PEI-MWCNTs | Oropharyngeal aspiration | 2 mg/kg body weight | PBS with or without 0.6 mg/mL BSA and 0.01 mg/mL DPPC | 40 h or 21 days | Male C57BL/6 mice aged 8 weeks | Obvious lung fibrosis induced by cationic PEI-MWCNTs, whereas reduced pulmonary fibrosis observed in the group of MWCNT-COOH. | [167] |
Tau-MWCNTs and raw MWCNTs | Intratracheal instillation | 0.125, 0.25, 0.5 or 1 mg/kg body weight | PBS | 1, 7, 14 or 28 days | Male CD-1 (ICR) mice of body weight 18∼22 g | Less toxic induced by Tau-MWNTs than insoluble raw MWNTs | [168] |