Table 6.
Potential toxicity of AgNPs in vivo and in vitro
| Objects | Exposure | Toxicity | References | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Animal model | In vitro/vivo | Cell lines/Tissues | Size; Shape | Dosages | Route | Time | Effect | Toxicity manners | |
| Pig | In vitro and vivo | HEKs and porcine skin | 20, 50 and 80 nm | 0.34, 1.7 μg/mL | Incubation; skin contact | Acute: 18 and 24 h; chronic: 14 d |
Focal inflammation | Dose-dependent | 350 |
| Mice | In vivo | Liver | Less than 30 nm | 10 ppm | Skin contact | 2, 7 and 14 d | Central venous dilation; hyperemia, cell swelling, Kupffer and inflammatory cells increase | Time-dependent | 332 |
| Mice | In vivo | Spleen, liver, lung and kidney | 12-20 nm | 7.5, 30 and 120 mg/kg | Intravenous administration | 7 and 14 d | Induction of inflammatory reactions in lung and liver cells | Gender-, concentration- and time-dependent | 346 |
| Mice | In vivo | Lung | 10-20 nm; spherical | 10, 100, 1000 and 10,000 ppm | Intratracheally administration | 1, 3, 7 and 15 d | Acute lung inflammation and bronchitis; hyperplasia of alveolar epithelial cells | Dose-dependent | 330 |
| Mice | In vivo | Liver, spleen, kidneys, heart, lungs, testes, stomach, intestine and seminal vesicles | 3±1.57 nm; spherical | 11.4-13.3 mg/kg | Intravenous injection | 1, 28 d | Inflammatory response; alteration of hematological factors; change of gene expression; ROS generation | Dose-dependent | 351 |
| Mice | In vivo | Liver, kidneys and lung | 10, 75 and 110 nm; spherical | 25 μg/mice | Intravenous administration | 1, 3 and 7 d | Peripheral inflammation in liver, kidneys and lungs | Time-, concentration- and size-dependent | 343 |
| Mice | In vivo | Lung | 20 and 110 nm | 0.05, 0.15, 0.45 and 1.35 mg/kg | Intratracheal instillation | 1, 7 and 21 d | Alter SP-D level; deficit immune defense function | Size- and stabilization-dependent | 44 |
| Mice | In vivo | Brain, lung, liver, kidney and testis | 22, 42 and 71 nm | 0.25 mg/kg, 0.50 mg/kg, 1.00 mg/kg | Oral administration | 14 and 28 d | Induce organ toxicity and inflammatory responses | Dose-dependent | 352 |
| Mice | In vivo | heart, lung, kidney, liver and blood | 1.4-250nm | 11.4-13.3mg/kg body weight | Intravenous administration | 28 d | Induce gene expression; ROS generation; apoptosis | Dose-dependent | 351 |
| Mice | In vitro and in vivo | A549, BxPC-3; PC-3; Hep G2, CNE; AsPC-1; U-87 MG; SW480; EC109; MDA-MB-231; VSMC; HMEC; LO2; 293FT; tumor, brain, heart, kidney, lung, spleen, and liver | 19.2±3.8 Ång, spherical or ellipsoidal | 0-32ng/µl, 1.875 mg/kg | Intravenous administration | Acute: 24 h; chronic: 28 d | None | Dose- and time-dependent | 21 |
| Mice | in vivo | Lung | 20 and 110 nm, spherical | 0.1, 0.5 and 1.0 mg/kg | Inhalation | Acute: 40 h; chronic: 21 d | Pulmonary fibrosis | Size- and coating-dependent | 353 |
| Mice | in vivo | Kidney, liver and spleen | 2.45-19.53 nm | 0.37, 0.65, 13 and 21 mg/kg | Oral administration | 27 d | Tissue destruction; cell necrosis and apoptosis | dose-dependent | 354 |
| Rat | In vivo | Brain | >100 nm | 5 and 50 mg/kg | Oral administration | 79 d | Cell death, disturbed neurotransmitter and cytokine production, ROS generation | -- | 355 |
| Rat | In vivo | Sperm and testicular tissue | 60-80 nm | 30, 125 and 300 mg/kg | Intraperitoneal injection | 28 d | Decrease normal sperm morphology, sperm vitality and sperm count | Dose-dependent | 348 |
| Rat | In vivo | Kidneys, liver and blood | 20-65 nm | 2,000 mg/kg | Intraperitoneal administration | 3 d | Liver and kidney damage | Time- and dose-dependent | 356 |
| Rat | In vivo | Lung, spleen, liver, kidney, thymus and heart | 6.3-629 nm | 0.5 mg/kg | Intravenous administration | 24 h | Liver and kidney damage; chromosome breakage; genotoxicity | Dose-dependent | 357 |
| Rat | In vivo | Epididymal sperm | 20-30 nm | 50, 100 and 200 mg/kg | Oral administration | 90 d | Sperm anomalies; decrease sperm viability | Dose-dependent | 37 |
| Rat | In vivo | Brain | 3-10 nm, spherical | 1 and 10 mg/kg | Intragastric administration | 14 d | Neuron shrinkage; cytoplasmic or foot swelling of astrocytes | Dose-dependent | 38 |
| Rats | In vivo | Kidney, liver and blood | 20-60 nm, spherical | 2,000 mg/kg bw, twice injections | Intraperitoneal injection | 5 d | Liver and kidney damage; blood parameters disrupt | Dose- and time-dependent | 356 |
| Rat | In vivo | Spleen, liver, and lymph nodes and blood | 20 nm and 100 nm | 6 mg/kg | Intravenous administration | 28 d | Suppression of the natural killer cell activity; stimulate LPS mitogen; increase cytokine production | Dose-dependent | 358 |
| Rat | In vivo | Liver and kidney | 56 nm | 30, 125 and 500 mg/kg | Oral administration | 90 d | Liver damage; bile-duct hyperplasia | Dose- and gender-dependent | 341 |
| Rat | In vivo | Kidney | 52.7-70.9 nm | 10 ml/kg | Oral administration | 90 d | Deposite in kidneys | Dose-dependent | 340 |
| Female ICR mice; male guinea pigs | In vivo | Oral, skin and eye | 10-20 nm, spherical | 5,000 mg/kg (oral); 50 and 5,000 ppm (eye); 50 and 100,000 ppm (skin) |
Oral administration; eye drops; skin contact |
1, 2 and 3 day | Conjunctivae irritation | — | 326 |
| Male ICR mice | In vivo | Blood, liver, spleen, kidney, lungs and brain | 10, 40 and 100 nm, spherical | 10 mg/kg | Intravenous injection | 24 h | Bleeding or necrosis of multiple internal organs | Size- and tissue-dependent | 331 |
| BN and SD rats | In vivo | Lung | 20, 110 nm, spherical | 0.1 mg/kg or 90 breaths/minute | Intratracheal administration | 1, 7 and 21 d | Lung eosinophilia and bronchial hyperresponsiveness; distruction of blood/alveolar epithelial permeability barrier | Dose- and size-dependent; rat strains related | 46 |
| Mice and guinea pigs | in vivo | Lung, lymph node, heart, liver and kidney | 10-20 nm, spherical | 5,000 mg/kg, 5000 ppm | Oral administration, eye and skin contact | 14 d | No mortality and toxic signs | 326 | |
| Freshwater fish | In vivo | Embryo | 25.9-36.7 nm, spherical | Acute: 0.3, 0.6, 1.2, 2.4 and 4.8 mg/L; subchronic: 0.05, 0.1, 0.25 and 0.5 mg/L | Incubation | 14 d | Liver damage; deplete glutathione; deactivate lactate dehydrogenase and antioxidant enzymes | Time- and dose-dependent | 39 |
| Japanese medaka | in vivo | Embryo | 20-37 nm, spherical | 0, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/L | Oral administration | 48 h | death | dose-dependent | 327 |
| Zebrafish | In vivo | Embryo | 20 and 110 nm, spherical | 0.08, 0.4, 2, 1,0 and 50 mg/L | Hatch | 5 d | Multiple developmental abnormalities | Size- and surface coating-dependent | 359 |
| Zebrafifish | In vitro and in vivo | Brain, heart, yolk and blood of embryo | 5-20 nm | 5, 10, 25, 50 and 100 µg/mL | Hatch | 24, 48 and 72 h | Multiple developmental abnormalities | Concentration-dependent | 43 |
| Drosophila melanogaster | in vivo | Parents, egg and offspring | 2-20 nm | 10, 20, 30, 40, 50 and 100 mg/L | Oral administration | 5,10, 15, 30, 45, 60 and 95 min | Abdominal pigmentation | Dose-dependent | 360 |
| Drosophila melanogaster | In vivo | Germline stem cell; testis | 20 nm | 2, 3.5 and 5 mg/L | Oral administration | 24h, 5 d | Delay the development of the F1 offsprings; ROS generation; premature GSC differentiation | Dose-dependent | 42 |
| Caenorhabditis elegans | In vivo | The worms' body | 96.4±35.6 nm, spherical | 0-1mg/L | Culture | 6 and 24 h | DNA damage, ROS generation, inhibition of growth | Dose- and time-dependent | 361 |
| Caenorhabditis elegans | In vitro | The worms' body | < 100 nm, spherical | 0.025, 0.05 and 0.075 µg/mL | Culture | 24 h | ROS generation; DNA damage | Size-dependent | 152 |
| — | In vitro | rat brain microvascular endothelial cells, pericytes, and astrocytes | 7±2 nm | 1 and 10 μg/mL | Incubation | 24 h | Trx system, Nr4a1 and Dusp1 regulaion , inflammation and apoptosis | Dose-dependent | 338 |
| — | In vitro | Mouse ESCs | 20.2 ±4.1 nm, spherical | 5.0 µg/ml | — | 24 h | Heat shock protein and the metallothionein families regulation, induce oxidative stress and apoptosis | Dose-dependent | 362 |
| — | In vitro | Mouse microglia N9 cell line, N27 neuronal cells | 49.7±10.5 nm, spherical | 50 μg/mL | Incubation | 24 h | Nitric oxide and TNFα production | Dose-dependent | 363 |
| — | In vitro | Mouse lymphoma cell line, human lymphoblastoid cells | 20, 50 and 100 nm, spherical | 0-400 μg/mL | Incubation | 4, 8, and 24 h | DNA mutants | Size-, concentration- and coating-dependent | 47 |
| — | In vitro | Rat primary cerebral astrocytes | 24.18±4.14 nm, spherical | 0.01, 0.1, 1 and 10 mg/mL | Incubation | 24 h | Neuroinflammation and apoptosis; increase caspase activities | Dose-dependent | 337 |
| — | In vitro | Primary astrocyte cell, rat glioma C6 cell line | 6.9-8.7 nm, spherical | 0.1, 1, 10, 50, 75 and 100 µg/mL | Incubation | 24 h | Necrosis and apoptosis | Dose-dependent | 364 |
| — | In vitro | Murine brain ALT astrocytes, murine microglial BV-2 cells and mouse neuroblastoma Neuro-2a (N2a) cells | 3-5 nm | 0.5, 1, 5, 10 and 12.5µg/mL | Incubation | 24 h | Cytokine secretion, Aβ amyloid deposition, inflflammatory response | Dose-dependent | 339 |
| — | In vitro | UMR-106 | 6 nm, cubic | 10, 25, 50, 100, 150 and 225 μM | Incubation | 24h | Decrease lysosomal and mitochondrial activity | Dose-dependent | 365 |
| — | In vitro | U937 cell | 4,20 and 70 nm, round | 1.56, 3.12, 6.25, 12.5, 25 and 50 µg/mL | Incubation | 24 h | Oxidative stress; cytokines release | Size-dependent | 50 |
| — | In vitro | HepG2 cell line | 20 nm | 2.5 to 50 µg/cm3 | Incubation | 24 h | Endogenous antioxidant defence regulation | Dose-dependent | 366 |
| — | In vitro | Jurkat T, NCI-H460, HeLa cells, HepG2, MCF-7, Beas-2B | 5-10 nm | 0.2, 0.5 and 1 mg/L | Incubation | 4, 12 and 24 h | DNA damage; p38 MAPK activation; cell arrest; apoptosis | Time- and concentration- dependent | 27 |
| — | In vivo | Human lymphocytes and sperms | 8-10 nm | Density gradient: 1:9, 1:3, 1:1 | — | 30 and 60 mins | Cell viability decrease | Concentration- and time-dependent | 367 |
| — | In vitro | Pk15 | 61.2±33.9 nm, nonuniform | 50 mg/L | Incubation | 24 and 48 h | Genotoxicity in Pk15 cells | Dose-dependent | 342 |
| — | In vitro | Zebrafish ovarian follicle cells | 30-55 nm | 30 μg/mL | Incubation | 2 h | Apoptosis of ovarian follicle cells; germinal vesicle breakdown | Concentration-dependent | 349 |
*NOTE: UMR 106, rat osteosarcoma cells; MDA-MB-231, triple negative breast cancer cell line; PMBC, peripheral blood mononuclear cell; HepG2, human liver cancer cell line; Jurkat T, human T lymphocyte cell line; NCI-H460, human lung cancer cell line; MCF-7, human breast cancer cell line; Beas-2B: human bronchial epithelial cells; SPD, surfactant protein-D; U937, human histiocytic lymphoma cell line; Pk15, pig kidney cell line; BV-2, murine microglial cell line; N2a cells, mouse neuroblastoma; HEKs, human embryonic kidney cells; A549, human lung carcinoma; BxPC-3, human pancreas adenocarcinoma cells; PC3, prostate adenocarcinoma cells; HepG2, hepatocellular carcinoma cells; ESCs, embryonic stem cell; CNE, nasopharyngeal carcinoma cells; AsPC-1, pancreas adenocarcinoma cells; U-87 MG, glioblastoma cells; SW480, colorectal adenocarcinoma cells; EC109, esophageal cancer cells; VSMC, vascular smooth muscle cells; HMEC, human microvascular endothelial cells; LO2, hepatocytes; 293FT, embryonic kidney cells.