Table 2.
Type of SiNPs | Exposure route | Primary particle size | Source | Species and Strain | Exposure dose | Exposure duration | Organ(s)/sample(s) | Effect(s)/endpoint(s) | Assay (s)/method(s) | Results | References |
---|---|---|---|---|---|---|---|---|---|---|---|
C-SiNPs | Oral | 20 and 100 nm | E&B Nanotech | Rat; SD (female and male) | 500 and 1000 mg/kg bw | 1 h–10 days | Animal | Clinical signs | Observation | No animal death | Lee et al. (2014) |
Lungs, liver, brain, kidneys, testis and spleen | Tissue distribution | Molybdenum blue method | NPs detected in lungs, liver, spleen and kidneys | ||||||||
NP Localization | TEM | NPs detected in the nuclei of hepatocytes | |||||||||
Urine and feces | Excretion kinetics | Molybdenum blue method | Most NPs excreted via feces | ||||||||
C-SiNPs | Oral | 20 and 100 nm (uncoated or l-arginine coated) | E&B Nanotech | Mice; C57BL/6 | 750 mg/kg bw | Daily for 14 days | Blood | WBCs count | Serum analyzer | Increase | Kim et al. (2014b) |
Pro-inflammatory response(s) | Multiplex analysis | Differential expression of cytokines | |||||||||
Spleen | Oxidative stress | DCFH-DA assay | Increase | ||||||||
Oxidative stress | SOD and GPx assay | No effect | |||||||||
Oxidative stress | Griess reagent/NO production | Increase | |||||||||
C-SiNPs | Oral | 12 nm | ABC Nanotech | Rat; SD | Acute-1959 and 2061; Sub-acute-489.8, 979.5, 1959; Sub-chronic: 244.9, 489.8 and 975.9 mg/kg bw | Acute—14 days Sub-acute—daily for 14 days Sub-chronic: daily for 13 w |
Blood | Blood cell count | Hematoanalyzer | No effect | Yun et al. (2015) |
Organ damage bio-markers | Serum analyzer | No effect | |||||||||
Urine | Urinalysis | Urine analyzer | No effect | ||||||||
Eye | Ophthalmology | Morphological examination | No effect | ||||||||
Major organs | Tissue distribution | ICP-MS | NPs not detected | ||||||||
Urine and feces | Excretion kinetics | ICP-MS | Most NPs excreted via feces | ||||||||
C-SiNPs | Oral gavage | 20 and 80 nm, coated with l-arginine | E&B Nanotech | Rats; Crl:CD(SD) | 500, 1000 and 2000 mg/kg bw | Daily for 90 days | Animal | Clinical signs | Observation | No animal death | Kim et al. (2014c) |
Blood | Blood cell count | Hematoanalyzer | No effect | ||||||||
Organ damage bio-markers | Serum analyzer | No effect | |||||||||
Eye | Ophthalmology | Observation of ocular fundus | No effect | ||||||||
All major organs | Necropsy | Weighing organs | No effect | ||||||||
Histopathology | H & E staining | No effect | |||||||||
C-SiNPs | Intratracheal | 9,15, 30 and 55 nm | AkzoNobel AB | Rat; Wistar (female) | 360 µg in 500 ml of saline | 3 days | Blood | Blood cell count | Hematoanalyzer | Increase of polymorphonulcear neutrophils and lymphocytes | Maser et al. (2015) |
Lungs | Histopathology | H & E staining | Mild increase of granulomatous inflammation | ||||||||
Genotoxicity | Comet assay | No effect | |||||||||
Bone marrow | Genotoxicity | Micronucleus test | No effect | ||||||||
C-SiNPs | Dermal | 20 nm, coated with l-arginine | E&B Nanotech | Rat; Sprague–Dawley (SD) | 500 mg, 1000 mg, and 2000 mg/kg bw | Daily for 90 days | Animal | Clinical signs | Observation | No animal death | Ryu et al. (2014) |
Blood | Blood cell count | Hematoanalyzer | No effect | ||||||||
Organ damage bio-markers | Serum analyzer | No effect | |||||||||
All major organs | Necropsy | Organ weighing | No effect | ||||||||
Histopathology | H & E staining | No effect | |||||||||
C-SiNPs | Dermal | 20 and 100 nm (uncoated or l-arginine coated) | E&B Nanotech | Rat | 2000 (coated) and 1000 mg/kg bw(uncoated) | Daily for 28 d | Brain | Blood–brain barrier damage | Evans blue staining | No effect | Shim et al. (2014) |
Tissue distribution | TEM-EDX | NPs not detected | |||||||||
C-SiNPs | Intraperitoneal | 50 nm | Polysciences | Mice; Male tuck ordinary | 0.25 mg/kg bw | 24 h | Blood | Blood cell count | Hematoanalyzer | Increase of leukocytes | Nemmar et al. (2016) |
Organ damage bio-markers | Serum analyzer | Increase of CK, ALT and AST | |||||||||
Lungs, heart, liver, kidneys, and brain | Oxidative stress | LPO, SOD and catalase assay | Increase | ||||||||
Pro-inflammatory response(s) | ELISA | Differential expression of IL-6, TNF-α and IL-1β | |||||||||
Genotoxicity | Comet assay | Increase | |||||||||
C-SiNPs | Intravenous | 64 nm | Laboratory synthesis | Mice; ICR (male and female) | 0, 29.5, 103.5, and 177.5 mg/kg bw | 14 days | Blood | Organ damage bio-markers | Serum analyzer | Increase of LDH, ALT and AST | Yu et al. (2013) |
Liver, spleen, kidneys, heart, lungs, and brain | Histopathology | H & E staining | Tissue damages observed | ||||||||
CD-68 positive cells | CD-68 staining | Increase in liver and spleen | |||||||||
NP localization | TEM | NPs detected in liver macrophages and in the endothelial cells of lungs and kidneys | |||||||||
Tissue distribution | ICP-OES | Si detected in liver and lungs | |||||||||
S-SiNPs | Intratracheal | 50 nm, with or without amine modification | Laboratory synthesis | Mice; C57BL/6 (male) | 4 and 20 mg/kg bw | 24 h | Lungs | Inflammation | BALF cell count and LDH assay | Dose-dependent increase of total cell number, macrophages, neutrophils and LDH release | Morris et al. (2016) |
Oxidative stress | ROS/RNS production | Dose-dependent increase | |||||||||
S-SiNPs | Intratracheal | 58 nm | Laboratory synthesis | Mice; C57 (male) | 2 mg/kg bw | Once every 3 days for 45 days | Testis | Histopathology | H & E staining | Decrease in mature sperm and primary spermatocytes | Zhang et al. (2016) |
Meiotic regulating factors | Western blot | Cell cycle arrest observed | |||||||||
Oxidative stress | DCFH-DA assay | Increase | |||||||||
Sperm | Quality evaluation | Microscopy | No effect | ||||||||
S-SiNPs | Intratracheal | 43 nm | Laboratory synthesis | Mice; BALB/c(female) | 0, 7, 21, and 35 mg/kg bw | Once every 3 days for 15 days | Lungs, liver and heart | Histopathology | H & E staining | Increase of Inflammation | Yang et al. (2016) |
Organ damage bio-markers | Serum analyzer | Increase of BUN, CREA, uric acid, and AST | |||||||||
NP localization | TEM | NPs detected in cytoplasm and lysosomes | |||||||||
Macrophage activation | Immunohistochemistry | Increase | |||||||||
Inflammatory response | Multiplex flow cytometry | Increase of IL-8, TNF-α and IL-6 | Duan et al. (2014a, b) | ||||||||
S-SiNPs | Intravenous | 62 nm | Laboratory synthesis | Mice; ICR | 29.5, 103.5, and 177.5 mg/kg bw | 14 days | Heart | Autophagy | LC3 and VEGFR2 positive staining | Increase of LC3 | |
TEM | Increase of autophagic ultrastructures | ||||||||||
Cell cytoskeleton staining | Weakening of F actin | ||||||||||
MMP measurements | Dose-dependent decrease | ||||||||||
LC3-II/LC3-I ratio | Increase | ||||||||||
M-SiNPs | Intragastrical | Spherical 83 nm, short rods (AR 1.75) and long rods (AR 5) | Laboratory synthesis | Mice; ICR (male) | 40 mg/kg bw | 14 days | Blood | Blood cell count | Hematoanalyzer | No effect | Li et al. (2015) |
Organ damage bio-markers | Serum analyzer | Increase of LDH release and CREA | |||||||||
Liver, kidneys, spleen, lungs and small intestine | Histopathology | H & E staining | Gross tissue damage in kidneys | ||||||||
Tissue distribution and excretion kinetics | ICP-OES and TEM | shape-dependent distribution and clearance in organs | |||||||||
M-SiNPs | Intravenous | 1.5 (short rods) and 5 (long rods) aspect ratio; standard or PEGylated | Laboratory synthesis | Mice | 20 mg/kg bw | 2 h, 24 h and 7 days | Blood | Blood cell count | Hematoanalyzer | No effect | Huang et al. (2011) |
Organ damage bio-markers | Serum analyzer | Increase of TBIL, CREA and BUN | |||||||||
Liver, spleen, lungs and kidneys | Histopathology | DAPI | Gross tissue damage in kidneys | ||||||||
Tissue distribution | ICP-OES | PEGylation reduced distribution in liver and spleen | |||||||||
Urine and feces | Excretion kinetics | TEM/EDX | Short rods cleared rapidly than long rods | ||||||||
M-SiNPs | Intraperitoneal | ~198 nm | Laboratory synthesis | Mice; BALB/C | 150, 300, and 600 mg/kg bw | 2 and 12 days | Blood | Organ damage bio-markers | Serum analyzer | Increase of AST, ALT BUN and CREA | Chen et al. (2015) |
Kidneys | Histopathology | H & E staining | Detection of renal interstitial fibrosis | ||||||||
Tissue damage | Masson’s trichrome staining | Dose and time-dependent increase in kidney injury | |||||||||
Pr-SiNPs (NM 200 & 201), Py-SiNPs (NM 202 & 203) | Oral gavage | 18–24 nm | JRC repository | Rat; SD (male) | 5, 10, and 20 mg/kg bw | 0, 24, and 45 h | Blood | Oxidative stress | LPO assay | No effect | Tarantini et al. (2015a, b) |
Liver, kidneys, spleen, intestine, blood and bone marrow | Histopathology | H & E staining | No effect | ||||||||
Genotoxicity | Alkaline, FpG modified comet assay and micronucleus test | No effect | |||||||||
Pr-SiNPs (NM 200) | Oral gavage | 10–15 nm | JRC repository | Rat; Wistar | 100, 300, or 1000 mg/kg bw at a dose volume of 10 mL/kg bw | Daily for 14 days (from gestation period 6–19) | Animal | Clinical signs | Observation | No animal death | Hofmann et al. (2015) |
Body weight | Observation | No effect | |||||||||
Gravid uterus | Necropsy | Cesarean | No effect | ||||||||
Fetus | Fetus gross damage | Morphological examinations | No effect | ||||||||
Py-SiNPs | Exposure via food | 7 nm and NM 202 (10–25 nm) | JRC repository | Rat; SD | Sub-acute: 100, 1000,2500 mg/kg bw Sub-chronic: 2500 mg/kg bw |
Sub-acute: daily for 28 days Sub-chronic: daily for 84 days |
Blood | Organ damage bio-markers | Serum analyzer | No effect | Zande et al. (2014) |
Plasma IgG and IgM and cytokine analysis | ELISA | No effect | |||||||||
Liver | Transcriptomic analysis | mRNA quantification kit | No effect | ||||||||
Liver, jejunum, kidneys and spleen | Histopathology | H & E staining | Presence of fibrosis in the liver of NM 202 treated rats | ||||||||
Liver, spleen, lungs, brain and testis | Tissue distribution | ICP-MS | NM 202 detected in lungs, kidneys and spleen; SAS only in the spleen | ||||||||
Py-SiNPs | Intravenous | 13 ± 5 nm | Vekton Ltd | Rat; Wistar | 7 mg/kg bw | 7, 30 and 60 days | Blood | Hemodynamics | Blood pressure measurement and heart rate | No effect | Zhuravskii et al. (2016) |
Blood cell count | Hematoanalyzer | No change | |||||||||
Organ damage bio-markers | Serum analyzer | Increase of ALP at 7 d | |||||||||
Liver, heart, spleen, lungs and kidneys | Tissue distribution | Atomic absorption spectrometry | Si detected in liver, lungs and spleen | ||||||||
NP localization | SEM | NPs detected in hepatocytes | |||||||||
Histopathology | H & E staining | Induction of fibrosis | |||||||||
SiNPs | Oral gavage | 70 nm, 300 and 1000 nm with or without carboxyl or amine groups | Micromod Partikeltechnologie | Mice; BALB/c | 2.5 mg/mouse | Daily for 28 days | Blood | Blood cell count | Hematoanalyzer | No effect | Yoshida et al. (2014) |
Organ damage bio-markers | Serum analyzer | No effect | |||||||||
All major organs | Histopathology | H & E staining | No effect | ||||||||
Intestine | Intestinal absorption | Evented gut sac analysis | Absorption of coated 70 nm SiNPs | ||||||||
SiNPs | Oral gavage | 10–15 nm | TECNAN | Rat; Wistar (male) | 333.3 mg/kg bw | Daily for 5 days | Animal | Clinical signs | Observation | Symptoms of vomiting and severe lethargy | Hassankhani et al. (2014) |
Blood | Organ damage bio-markers | Serum analyzer | Increase | ||||||||
Kidneys, lungs and testis | Histopathology | H & E staining | Tissue damage observed | ||||||||
SiNPs | Intratracheal | Three SiNPs (30, 60, and 90 nm) and one fine-sized silica (600 nm) | Laboratory synthesis | Rat; Wistar (male) | 2,5 and 10 mg/kg bw | Daily for 16 days | Blood and Heart | Blood cell count | Hematoanalyzer | Increase of WBCs & platelets and decrease of hemoglobin &RBCs | Du et al. (2013) |
Oxidative stress | LPO, GSH, SOD and GSH-Px assay | Increase of MDA formation | |||||||||
Oxidative stress | NO/NOS | Increase of NO and decrease of NOS | |||||||||
Pro-Inflammatory response(s) | ELISA | Increase of TNF-a, IL-1b and IL-6 | |||||||||
Tissue distribution | ICP-OES | NPs detected in heart | |||||||||
SiNPs in paints | Oropharyngeal | 19 nm | SiNPs | Mice; BALB/c mice | 20 µg/aspiration | Once a week for 5 w | Lungs | Inflammation | BALF Cell count | Increase of macrophages and neutrophils | Smulders et al. (2014) |
Pro-inflammatory response(s) | ELISA | No effect | |||||||||
Tissue distribution | ICP-MS | NPs detected in lungs | |||||||||
SiNPs | Intranasal | 10 and 80 nm SiNPs | Nanoamor | Rat; Wistar (male) | 150 µg/50 µl PBS/rat | Daily for 30 days | Brain | Oxidative stress | LPO assay | Increase of MDA formation | Parveen et al. (2015) |
Xylenol orange assay | Increase of H2O2 levels | ||||||||||
GSH depletion | Increase | ||||||||||
SOD, CAT and GPx levels | Increase | ||||||||||
Pro-Inflammatory response(s) | RT-PCR and ELISA | Increase TNF-α, IL-1β and MCP-1 | |||||||||
Nuclear binding activity | Immuno blot analysis | Increase | |||||||||
Tissue distribution | ICP-OES | Si detected in frontal cortex, corpus striatum and hippocampus | |||||||||
SiNPs | Topical | 70 nm, 300 and 1,000 nm | Micromod Partikeltechnologie | Mice; BALB/c | 250 mg/ear | Daily for 28 days | Skin | Apoptosis | TUNEL staining | Increase | Nabeshi et al. (2011b) |
Animal | Tissue distribution | In vivo Imaging | 70 nm SiNPs detected around the liver | ||||||||
Intravenous | 30 mg/kg bw | 24 h | |||||||||
NP internalization | TEM | 70 nm SiNPs detected in cytoplasm and nucleus of the parenchymal hepatocytes (liver) | |||||||||
SiNPs | Intravenous | 15 nm | Sigma-Aldrich | Rat; SD (male) | 50 mg/kg bw | 48 h | Blood | Blood cell count | Hematoanalyzer | Increase of WBC, lymphocytes, monocytes and neutrophils | Chen et al. (2013) |
Liver | CD-68 positive cells | CD-68 staining | Increase | ||||||||
Oxidative stress | GSH and SOD assay | Increase | |||||||||
Injury bio-markers | Proton-NMR spectroscopic analysis | Increase |
JRC Joint research commission, TEM Transmission electron microscopy, WBCs White blood cells, ICP-MS Inductively coupled plasma mass spectrometry, H & E Hematoxylin and eosin, EDX Energy dispersive X-ray spectroscopy, ELISA Enzyme linked immuno sorbent Assay, CD Cluster of differentiation, ICP-OES Inductively coupled plasma optical emission spectroscopy, BALF Bronchoalveolar lavage fluid, VEGFR Vascular endothelial growth factor receptor, MMP Mitochondrial membrane potential, DAPI-4′,6-diamidino-2-phenylindole, dilactate, SEM Scanning electron microscopy, TUNEL Terminal deoxynucleotidyl transferase dUTP nick end labeling, NMR Nuclear magnetic resonance