Table 3 Studies on effect (human health and environment) of various types of nanoparticles

Inorganic-based Nanoparticles

Ahamed et al. [31]

Bismuth oxide (Bi₂O₃)

MCF-7 cell line (a human breast cancer cell line with estrogen, progesterone, and glucocorticoid receptors)

• Reduces cell viability

• Induces membrane damage Dose-dependently

• Oxidative stress

• Reactive Oxygen Species generation

Eom & Choi [32]

Fumed and porous Silicon dioxide (SiO₂)

Human bronchial epithelial cell (Beas-2)

• Oxidative stress

• Induction of heme oxygenase-1 (HO-1)

Bengalli et al. [33]

Copper (CuO) and Zinc oxide (ZnO)

Reconstructed human epidermis model and fibroblast monolayer

• Deeply affect the epidermal tissue and the underlying dermal cells upon trans-epidermal permeation

Ferraro et al. [34]

Titanium dioxide (TiO₂)

Human neuroblastoma (SH-SY5Y) cell line

• Reactive Oxygen Species generation

• Apoptosis

• Induction of endoplasmic (ER) stress

• Neurotoxicity

Gambardella et al. [35]

Silicon dioxide (SiO₂)

Sea urchin Paracentrotus lividus sperms

• Reduced toxicity

• Neurotoxic damage

• Decrease of acetylcholinesterase (AChE) expression

• No effect on fertilization capability

• Induced of toxic effect on the offspring

Yusefi-Tanha et al. [30]

Zinc oxide (ZnO)

Soil samples and Soybean seeds

• Oxidative stress

• Significant particle size-, morphology-, and concentration-dependent influence on seed yield and lipid peroxidation

Oh et al. [36]

Citrate-coated silver (Ag)

Human embryonic stem cell (hESC)

• Oxidative stress

• Dysfunctional neurogenesis

Zhao et al. [37]

Silicon dioxide (SiO₂)

Lung bronchial epithelial cells (BEAS-2B)

• Disturbs global metabolism

• Oxidative stress

• Generation of reactive oxygen species

• Significantly perturbs mitochondrial dysfunction-related GSH metabolism and pantothenate and coenzyme A (CoA) biosynthesis

• Causes abnormality in mitochondrial structure and mitochondrial dysfunction

Ying et al. [38]

Superparamagnetic Iron oxide (SPIO)

A3 human T lymphocytes

• Causes concentration-dependent nanotoxicity

Jing et al. [39]

Copper oxide (CuO)

Lung adenocarcinoma cells (A549 cells) and human bronchial epithelial cells (HBEC)

• Significantly reduced cell viability

• Increased lactate dehydrogenase (LDH) release

• Reactive Oxygen species and IL-8 generation

Lojk et al. [40]

Silicon dioxide (SiO₂), Titanium dioxide (TiO₂), Silver (Ag), Polyacrylic acid (PAA) coated cobalt ferrite (CoFe₂O₄)

Human neuroblastoma (SH-SY5Y) cell

• Neurotoxicity

• Reactive Oxygen species formation

• Membrane damage

• Autophagy dysfunction for TiO2 P25 NPs

• Decrease of cell viability for TiO2 FG NPs

Tsai et al. [41]

Titanium dioxide (TiO₂) and Cerium dioxide (CeO₂)

BEAS-2B epithelial cell

• TiO₂ induces apoptosis and hypersecretion of mucus

• CeO₂ NPs reduce cytosolic Ca²⁺ changes and mitochondrial damage caused by TiO₂ NPs

Sramkova et al. [42]

Titanium dioxide (TiO₂), Silicon dioxide (SiO₂), magnetite (Fe₃O₄) and gold (Au)

Human renal proximal tubule epithelial TH1 cell line

• None of the NPs induced any DNA strand breaks and oxidative DNA lesions regardless of the exposure (static and dynamic conditions)

• No cytotoxicity was observed, except for Fe₃O₄NPs

Bell et al. [43]

Silicon dioxide (SiO₂)

SH-SY5Y human neuroblastoma (ATCC CRL-2266)

Human epithelial type-2 (HEp-2) cells (ATCC CCL-23)

• Destabilizes mitochondrial membrane potential

• stimulates reactive oxygen species production

• Promotes cytotoxicity

Akhtar et al. [44]

Silicon dioxide (SiO₂)

Human lung epithelial cells (A549 cells)

• Lower concentration:

o Induction of reactive oxygen species

o Membrane damage

• Higher concentration:

o Reactive oxygen species generation

o GSH depletion

Gaiser et al. [27]

Silver (Ag) and cerium oxide (CeO₂)

Aquatic species: Daphnia magna neonates, fish, Carp (Cyprius carpio)

Human model: C3A human hepatocyte cell line and caco-2 human intestinal epithelial cells

• Ag is more cytotoxic than CeO₂

• Both particles when in diet have the potential to enter the body following ingestion

Dankers et al. [45]

CeO₂, Mn₂O₃, CuO, ZnO, Co₃O₄, and WO₃

Lung epithelium and dendritic cells

• Metal oxide NPs elicit minimal proinflammatory effects

Chen et al. [46]

Zinc oxide (ZnO)

Human umbilical vein endothelial cells (HUVECs)

• ZnO induces significant cellular ER stress

• Higher doses of ZnO induces apoptosis

Patil et al. [47]

Titanium dioxide (TiO₂) and zinc oxide (ZnO)

Lung fibroblast (MRC5)

• Impedes genomic DNA hypomethylation

Mohamed et al. [48]

Silicon dioxide (SiO₂)

Human monocytic leukemia cell line THP-1 and human alveolar epithelial (A549) cell line

• Low degree of cytotoxicity at all concentrations

• Stress-related cellular response at high concentrations

Mancuso & Cao [14]

Copper oxide (CuO)

Human bone marrow mesenchymal stem cells (hBMMSCs)

• Bigger sizes exhibit significant cytotoxicity at all concentrations

• Micro-sized particles exhibit very low cytotoxicity at the same concentration

Alshatwi et al. [49]

Aluminium oxide (Al₂O₃)

Human mesenchymal stem cells (hMSCs)

• Dose-dependent decreased cell viability

• Decreased mitochondrial membrane potential with increasing concentrations after 24 exposures

• Down-regulation in the expression of the antioxidant enzyme SOD

• Did not induce apoptosis

• Dose-dependent oxidative stress

Baber et al. [50]

Two amorphous silica coated (MagSilica 85, MagSilica 50) and uncoated iron oxide NPs (Fe₃O₄)

BEAS-2B (immortalized normal human bronchial epithelium)

• Little to no indications of cytotoxicity

• No induction of inflammatory response/oxidative stress

Corbalan et al. [51]

Amorphous Silicon dioxide (SiO₂)

Blood

• Induced an upregulation of selectin P expression and glycoprotein IIb/IIIa activation on the platelet surface membrane

• Platelet aggregation

Branica et al. [52]

Zinc oxide (ZnO)

Blood (Human lymphocyte)

• Higher concentrations increase cytogenetic damage and intracellular Zn²⁺ levels in lymphocytes

Gurunathan et al. [53]

Platinum (Pt)

Human acute monocytic leukemia (THP-1) macrophages

• Decreased cell viability and proliferation

• Induces cell death

• Oxidative stress

• Mitochondrial dysfunction

• Endoplasmic reticulum stress (ERS)

• Proinflammatory responses

Hussain et al. [54]

Cerium dioxide (CeO₂)

Human peripheral blood monocytes

• CeO₂ NPs at non-cytotoxic concentrations neither modulate pre-existing inflammation nor prime for subsequent exposure to lipopolysaccharides in human monocytes from healthy subjects

Zerboni et al. [55]

Zinc oxide (ZnO) and Cupper oxide (CuO)

Human alveolar epithelial cells, A549

• The presence of diesel exhaust particles (DEP) introduces new physicochemical interactions able to increase the cytotoxicity of ZnO and to reduce that of CuO NPs

Zielinska et al. [56]

Silver (Ag)

Human fetal osteoblast cells (hFOB 1.19)

• Cell death

• Reactive oxygen species production

Rajiv et al. [57]

Cobalt (II, III) oxide (Co₃O₄); Iron (III) oxide (Fe₂O₃), Silicon dioxide (SiO₂), and Aluminium oxide (Al₂O₃)

Human lymphocytes

• Co₃O₄ NPs showed a decrease in cellular viability and an increase in cell membrane damage followed by Fe₂O₃, SiO₂, and Al₂O₃ NPs in a dose-dependent manner

• Oxidative stress

• Lipid peroxidation

• Depletion of catalase

• Reduced glutathione

• Superoxide dismutase

Alarifi et al. [58]

Copper oxide (CuO)

Human skin epidermal cell line (HaCaT; passage no. 20)

• Decrease in cell viability

• Reduction in glutathione and induction in lipid peroxidation, catalase, and superoxide dismutase

• Apoptosis

• Necrosis

• Induces DNA damage mediated by oxidative stress

Sun et al. [59]

Zinc oxide (ZnO), Fe₂O₃, Iron (II, III) oxide (Fe₃O₄), Magnesium oxide (MgO), Aluminium oxide (Al₂O₃), Copper (II) oxide (CuO)

Human cardiac microvascular endothelial cells (HCMECs)

• Fe₂O₃, Fe₃O₄, and Al₂O₃ NPs did not have significant effects on cytotoxicity, permeability, and inflammation response

• ZnO, CuO, and MgO NPs produced cytotoxicity at a concentration-dependent and time-dependent manner and elicited permeability and inflammation response in HCMECs

Tolliver et al. [60]

Titanium dioxide – (TiO₂), Zinc oxide – (ZnO), Copper oxide – (CuO), Manganese oxide (Mn₂O₃), Iron oxide – (Fe₂O₃), Nickel oxide – (NiO), Chromium oxide – (Cr₂O₃)

Human lung cancer cell model (A549)

• All NPs aside from Cr₂O₃ and Fe₂O₃ showed a time- and dose-dependent decrease in viability

• All NPs significantly inhibited cellular proliferation

• Apoptosis

• Cell cycle alteration in the most toxic NPs

Rothen-Rutishauser et al. [61]

Cerium oxide (CeO₂)

Adenocarcinomic human alveolar basal epithelial (A549) cell line

• Generation of oxidative DNA damage

• Causes tightness of the lung cell monolayer

• Dose-dependent cellular response

Benameur et al. [62]

Cerium Oxide (CeO₂)

Human dermal fibroblasts

• Genotoxicity

• Reactive oxygen species production

• Lower doses of CeO₂ did not induce significant cytotoxicity

• Induces lipid peroxidation and decline of cellular glutathione level at concentrations above 0.00006 M

Gojova et al. [63]

Cerium oxide (CeO₂)

Human aortic endothelial cells (HAECs)

• Causes very little inflammatory response even at higher doses

Lee et al. [29]

Zinc oxide (ZnO)

Natural soil and seedlings of

buckwheat

• The effect of ZnO NPs on soil bacterial depends on the presence of plants

• The soil–plant interactive system helps to decrease the toxic effects of ZnO nanoparticles on the rhizobacteria population relative to soil systems not containing plants

Hildebrand et al. [64]

Magnetite (Fe₃O₄) and palladium magnetite (Pd/Fe₃O₄)

1) Human cell lines: Colon adenocarcinoma cells, CaCo-2 (HTB-37), Human keratinocyte cells, (HaCaT)

2) Fish cell line: Rainbow trout gills (RTgill-W1) cell line

• No initiation of reactive oxygen species production

• Little impact on the viability of colon adenocarcinoma cells, human keratinocyte cells, and the rainbow trout gills cell line

• No toxic effect was found

Lai et al. [65]

Titanium dioxide (TiO₂)

Human astrocytoma and human fibroblasts

• Induces cell death

• Apoptosis

• Necrosis

Ahamed et al. [66]

Copper oxide (CuO)

Human lung epithelial cells (A 459)

• Dose-dependent reduction in cell viability

• Induces oxidative stress

• Depletion of glutathione

• Induction of lipid peroxidation, Catalase and superoxide dismutase

• Induces cellular damage (indicated by the expression of Hsp70, the first tier biomarker of cellular damage)

Vergaro et al. [67]

Titanium dioxide (TiO₂)

Human bronchial epithelial cells (BEAS-2B)

• Induces a low photo reactivity and a toxic effect lower than Aeroxide P25 of the nano-TiO₂ powders

Dávila-Grana et al. [68]

Zinc oxide (ZnO), Titanium dioxide (TiO₂), Cerium dioxide (CeO₂), Aluminium oxide (Al₂O₃), Yttrium (III) oxide (Y₂O₃)

Jurkat cell line

• The combination of nanoparticles induces changes in cell signalling mediated by the MAPKs and nuclear factor-κB (NF-κB)

• Al₂O₃ NPs had a protective effect when combined with the ZnO NPs

• CeO₂ and Y₂O₃ Nps induced a synergistic effect on the toxicity and p38 activation

• TiO₂ nanoparticles increase the toxicity induced by ZnO nanoparticles but reduced the phosphorylation of the signalling proteins

Pierscionek et al. [69]

Cerium oxide (CeO₂)

Human lens epithelial cells

• Epithelial cells can sustain normal growth when exposed to lower concentrations of nanoceria

• Induces genotoxicity when exposed for longer periods

Rafieepour et al. [70]

Magnetite iron oxide (Fe₃O₄), polymorphous silicon dioxide (P-SiO₂)

Adenocarcinomic human alveolar basal epithelial (A549) cell line

• Reduces cell viability

• Reduces cellular glutathione content and mitochondrial membrane potential

• Increases reactive oxygen species generation in both single and combined exposures of Fe₃O₄ and P-SiO₂

• The toxic effects of combined exposure to these NPs were less than the single exposures

Ickrath et al. [71]

Zinc oxide (ZnO)

Human mesenchymal stem cells (hMSC)

• Induces cytotoxic effect at higher concentrations of 50mcg/mL

• Induces genotoxic effects in hMSC exposed to between 1 and 10mcg/mL ZnO-NP

Radeloff et al. [72]

Iron oxide (Fe₃O₄)

Human adipose tissue derived stromal cells (hASCs)

• No effect on the physiological functions of human adipose tissue derived stromal cell (hASCs)

Jin et al. [73]

Zinc oxide (ZnO)

Zebrafish larvae and human neuroblastoma cells SH-SY5Y

• Smaller sizes of ZnO showed slightly higher toxicity than the larger sizes

• Long ZnO NRs (l-ZnO NRs) harbours a remarkably potential risk for the onset and development of Parkinson’s disease at relatively high doses

Kumari et al. [74]

Cerium oxide (CeO₂)

Human neuroblastoma cell line (IMR32)

• Induces size- and dose-dependent toxicity (oxidative stress and genotoxicity)

• CeO₂ did not induce toxicity below 100 mg/mL concentration

• IMR32 cells are less sensitive to CeO₂ NPs

Fernández-Bertólez et al. [75]

Silica-coated iron oxide nanoparticles (SiO₂)

Human glioblastoma A172 cells

• Cytotoxicity (cell cycle disruption and cell death induction)

• Rarely induces genotoxic effects

• No alteration in the DNA repair process

Gliga et al. [76]

Nickel (Ni), nickel oxide (NiO)

Human bronchial epithelial cell line (BEAS-2B)

• Long-term exposures (six weeks) changes gene expressions

• Induces DNA strand breaks and alter cell cycle after six weeks of repeated exposure

• Nickel causes no effect on cell transformation (ability to form colonies in soft agar) or cell motility

Kennedy et al. [77]

Iron oxide (Fe₃O₄), zinc oxide (ZnO), Yttrium oxide (Y₂O₃), and cerium oxide (CeO₂)

Human aortic endothelial cells (HAECs)

• Induces oxidative stress

• Zinc oxide more toxic than yttrium oxide

• No effect on HAECs when exposed to Iron oxide and cerium oxide

Schanen et al. [78]

Titanium dioxide and cerium dioxide (TiO₂ and CeO₂)

PBMC blood product

• Low dose exposures modulate human innate and adaptive immunity (i.e., dendritic cells activation and primary CD4 T helper cell differentiation state)

Seker et al. [79]

Zinc oxide (ZnO)

Human periodontal ligament fibroblast cells (hPDLFs)

• Causes cell index decrease at concentrations of 50 to 100lg/mL

• Induces changes in cell morphology

• Induces harmful effects on cell viability and membrane integrity

• Necrosis

• Cell death (in terms of morphological change or cellular shrinkage) at doses higher than 50lg/mL

• Cytotoxicity depends on duration of exposure and concentration

Könen-Adıgüzel & Ergenel [80]

Cerium dioxide (CeO₂)

Human blood lymphocytes

• Induces genotoxicity even at 3–24 h exposure under in vitro conditions

Henson et al. [81]

Cupric (II) oxide (CuO), Polyvinylpyrrolidone (PVP) coated NPs

A three-dimensional model of the human small intestine, EpiIntestinalTM(SMI-100)

• Induces dose- and time-dependent viability of human cells

Gojova et al. [82]

Iron oxide (Fe₂O₃), Yttrium oxide (Y₂O₃), and Zinc oxide (ZnO)

Human aortic endothelial cells (HAECs)

• All three types of nanoparticles are internalized into HAECs and are often found within intracellular vesicles

• No inflammatory response after exposure to Fe₂O₃

• Y₂O₃ and ZnO nanoparticles elicit pronounced inflammatory response

Alarifi et al. [83]

Zinc Oxide (ZnO)

Human skin melanoma (A375) cells

• Decrease in cell viability

• Causes morphological changes

• Induces oxidative stress

• Reactive oxygen species generation

• Depletion of the antioxidant, glutathione

• Induces DNA damage at higher concentrations

Ãkerlund et al. [84]

Nickel (Ni) and nickel oxide (NiO)

Human bronchial epithelial cells (HBEC)

• Causes a release of inflammatory cytokines from exposed macrophages

Jiménez-Chávez et al. [85]

Titanium dioxide and Zinc oxide (TiO₂ and ZnO)

Human alveolar epithelial cells (A549)

TiO₂:

• Shows a higher persistence in cell surface and uptake

• Induces sustained inflammatory response (by means of TNF-Î ± , IL-10, and IL-6 release)

• Induces reactive oxygen species generation

ZnO:

• Shows a modest response and low number in cell surface

Both TiO₂ and ZnO:

• Concentration-dependent reduction in SP-A levels at 24 h of exposure to both TiO₂ and ZnO

• Cellular damage

• Loss of lung function

Hussain & Garantziotis [86]

Cerium dioxide (CeO₂)

Primary human monocytes

• Apoptosis (involving mitochondrial damage)

• Causes a loss in membrane potential

• Induces mitochondrial relocation of BAX

• Induces modulation in autophagic events

Abudayyak et al. [87]

Bismuth Oxide—Bi (III) oxide (Bi₂O₃)

a) HepG2 human hepatocarcinoma cells (ATCC HB-8065)

b) Caco-2 human colorectal adenocarcinoma cells (ATCC HTB-37)

c) A549 human lung carcinoma cells (ATCC CCL-185)

• Induces apoptosis in HepG2

• Induces necrosis in A549 and Caco-2 cells

• Causes significant changes in the levels of glutathione (GSH), malondialdehyde (MDA), and 8-hydroxydeoxyguanine (8-OHdG) in HepG2 and Caco-2 cells, except A549 cell

Fahmy et al. [88]

Copper/copper oxide (Cu/CuO)

Human diploid lung fibroblast normal cell lines (WI-38 cell) and human epithelial lung carcinoma cell lines (A549 cells)

• Suppresses proliferation and cell viability

• Cause DNA damage

• Induces generation of reactive oxygen species

• Induces oxidative stress

Božinović et al. [89]

Molybdenum trioxide (MoO₃)

Human keratinocyte (HaCaT) cell line

• Short exposure (up to 1 h) of keratinocytes to MoO₃ has no significant impact on cell survival

Ahamed et al. [90]

Iron oxide (Fe₃O₄)

Skin epithelial A431 and lung epithelial A549 cell lines

• Induces dose-dependent cytotoxicity (indicated by reduction in cell viability lactate dehydrogenase leakage assays)

• Induces dose-dependent oxidative stress

• Induces reactive oxygen species

• Induces lipid peroxidation

• Causes DNA damage in high concentrations

• Up-regulates the protein expression level of cleaved caspase-3

Pelclova et al. [91]

Titanium dioxide (TiO₂)

Exhaled breath condensate (EBC) and urine

• Induces elevation of Leukotrienes (LT) levels

• Induces inflammation and potential fibrotic changes in the lungs

Valdiglesias et al. [92]

Zinc oxide (ZnO)

Human neuroblastoma SHSY5Y cell line

• Apoptosis

• Decreases cell viability

• Induces cell cycle alterations

• Induces micronuclei production

• Induces H2AX phosphorylation and DNA damage

Verdon et al. [93]

Silver (Ag), Zinc oxide (ZnO), Copper oxide (CuO), Titanium dioxide (TiO₂)

1) Human acute myeloid leukemia suspension cell line, HL-60

2) Primary neutrophils from human blood

• Ag and CuO nanoparticles stimulate neutrophil activation

• TiO₂ do not induce neutrophil response in either cell type

• ZnO induces activation of HL-60 cells but does not activate primary cells

Siddiqui et al. [94]

Nickel oxide (NiO)

Cultured human airway epithelial (HEp-2) and human breast cancer (MCF-7) cells

• Apoptosis

• Cytotoxicity

• Reactive Oxygen species generation

• Oxidative stress

• generation and oxidative stress

• Dietary antioxidant curcumin can effectively abrogate NiO NP-induced toxicity

Park et al. [95]

Cerium oxide (CeO₂)

Human lung epithelial cells (BEAS-2B)

• Causes cell death

• Reactive oxygen species production

• Glutathione (GSH) decrease

• Induces oxidative stress-related genes (e.g., heme oxygenase-1, catalase, glutathioneS-transferase, and thioredoxin reductase)

• Apoptosis

Fakhar-e-Alam et al. [96]

Zinc oxide (ZnO)

Melanoma cells and human foreskin fibroblasts

• Induces reactive oxygen species production after UV-A-irradiation

• Causes loss of mitochondrial membrane potential

• Induces significant loss of cell viability

Hackenberg et al. [97]

zinc oxide (ZnO)

Human mucosa of the inferior nasal turbinate

• Repetitive exposure to low concentrations of ZnO-NPs results in persistent or ongoing DNA damage

Andujar et al. [98]

Welding-related NPs (essentially, Iron (Fe), Manganese (Mn), Chromium (Cr) oxide)

The lung of arc welders exposed to fume-issued NPs

• Induce the production of a pro-inflammatory secretome

• All, but magnetite NPs, induce an increased migration of macrophages

• NP-exposed macrophage secretome has no effect on human primary lung fibroblasts differentiation

Sharma et al. [99]

Zinc oxide (ZnO)

Human hepatocarcinoma cell line (HepG2)

• Decreases cell viability

• Apoptosis

• Induces DNA damage

• Production of reactive oxygen species

• Decreases mitochondria membrane potential

• Activates JNK and p38

• Induces p53-Ser15 phosphorylation

Senapati et al. [100]

Zinc oxide (ZnO)

Human monocytic cell line, THP-1

• Induces oxidative and nitrosative stress

• Causes an increase in inflammatory response (via activation of redox sensitive NF-kB and MAPK signalling pathways)

Carbon-based Nanoparticles

Vlaanderen et al. [101]

Multi-walled carbon nanotubes (MWCNTs)

Breathing zone measurement of inhalable particulate matter, whole blood samples, and assessment of lung function of workers

• Significant upward trends for immune markers C–C motif ligand 20 (p = .005), basic fibroblast growth factor (p = .05), and soluble IL-1 receptor II (p = .0004) with increasing exposure to MWCNTs

• Effect on lung health and immune system

Asghar et al. [102]

Carbon Nanotubes (CNT), Graphene Oxide (GO)

Human sperm

• Both SWCNT-COOH and reduced GO Causes no effect to sperm viability at lower concentrations

• SWCNT-COOH generates significant reactive superoxide species at a higher concentration

• Reduced graphene oxide does not initiate reactive species in human sperm

Periasamy et al. [103]

Carbon nanoparticles (CNPs)

Human mesenchymal stem cells (hMSCs)

• Reduces cell viability

Beard et al. [104]

Carbon nanotubes and nanofibers (CNT/F)

Sputum and blood

Inhalable rather than respirable CNT/F associated with:

• Fibrosis

• Inflammation

• Oxidative stress

• Cardiovascular biomarkers

Zhang et al. [105]

Single Wall Carbon nanotube (SWCNT)

Human ovarian cancer cell line OVCAR3

• Sensitises OVCAR3 cells to the chemotherapeutic compound paclitaxel (PTX) resulting in increased cell death

• Apoptosis

de Gabory et al. [106]

Double-Walled Carbon Nanotubes (DWCNTs)

Human nasal epithelial cells (HNEpCs)

• Dose-dependent decrease in cell metabolic activity and cell growth

• Stimulation of mucus production

• Significant increase in Reactive Oxygen Species

• Increased effect after 12-day exposure

Eldawud et al. [107]

Single Wall Carbon nanotubes (SWCNTs)

Immortalised human lung epithelial cell (BEAS-2B)

• Reducing cell viability

• Changes cell structure, cycle and cell–cell interactions

Pacurari et al. [108]

Multi-walled carbon nanotubes (MWCNTs)

Human microvascular endothelial cells (HMVEC)

• Increase in endothelial monolayer permeability and migration in HMVEC

• Induces endothelial cell permeability

• Production of reactive oxygen species

• Actin filament remodelling

Reamon-Buettner et al. [109]

Multi-walled carbon nanotubes (MWCNTs)

Human peritoneal mesothelial cells LP9

• Inhibition of cell division

• Induces premature cellular senescence

Phuyal et al. [110]

Multi-walled carbon nanotubes (MWCNTs)

Human bronchial epithelial 3-KT (HBEC-3KT) cells

• Alters both the proteome and the lipidome profiles of the target epithelial cells in the lung

Witzmann & Monteiro-Riviere [111]

Multi-walled carbon nanotubes (MWCNTs)

Cryopreserved neonatal human epidermal keratinocytes

• Alters the protein expression in epithelial cells

• Significant effect on the expression of cytoskeletal elements

Snyder et al. [112]

Multi-walled carbon nanotubes (MWCNTs)

Human bronchial epithelial primary cells

• Negatively impacts the ability of human airway epithelium to form a monolayer barrier

• Altered cell morphology

• Cytoskeletal disruption

Snyder et al. [113]

Multi-walled carbon nanotube (MWCNTs)

Human bronchial epithelial cells (BECs)

• Causes mitochondrial dysfunction that leads to mitophagy

Ghosh et al. [28]

Multi-walled carbon nanotubes (MWCNTs)

Allium cepa bulbs

• Cyto-genotoxicity

• Induces significant DNA damage

• Induces micronucleus formation

• Chromosome aberration

• Internucleosomal fragments formation, indicative of apoptotic cell death

Yu et al. [114]

Multi-walled carbon nanotubes (MWCNTs)

Immortalized human mesothelial cell line (Met-5A)

• Causes significant cytotoxic effects on Met-5A cells

• Higher concentrations induce cellular membrane permeability and disturbance of mitochondrial metabolism

• No significant toxic effect at low concentrations

• Reactive oxygen species formation

Rizk et al. [115]

Multi-walled carbon nanotube (MWCNTs)

Normal human dermal fibroblast (NHDF) cells

• Induces induced massive loss of cell viability

• DNA damage

• Programmed cell death

Jos et al. [116]

Single wall carbon nanotubes (SWCNTs)

Human Caucasian colon adenocarcinoma (Caco-2) cell line

• Increase in Lactate dehydrogenase (LDH) leakage

• Cytotoxicity

• Protein content only modified at higher concentrations

Vankoningsloo et al. [117]

Multi-walled carbon nanotubes (MWCNTs)

1) Immortalised human keratinocytes (IHK)

2) SZ95 sebocytes

3) Reconstructed human epidermises (RHE)

• Induces cytotoxicity in human keratinocytes

• No cytotoxic effects in SZ95 sebocytes or in stratified epidermises reconstructed in vitro

Herzog et al. [118]

Single-walled carbon nanotubes (SWCNTs), Carbon black (CB)

1) Human lung epithelial cells (A549)

2) Normal human primary bronchial epithelial cells (NHBE)

• Low oxidative stress

• Cell responses are strongly dependent on the vehicle used for dispersion

• The presence of dipalmitoyl phosphatidylcholine (DPPC) increased intracellular reactive oxygen species (ROS) formation

Müller et al. [119]

Single-walled carbon nanotubes (SWCNTs) and Titanium dioxide (TiO₂)

Human epithelial lung cells (A549), human monocyte-derived macrophages (MDMs) and monocyte-derived dendritic cells (MDDCs)

• SWCNTs and TiO2 can penetrate into A549, MDMs, and MDDCs

• Induces the production of reactive oxygen species

Baktur et al

Single-walled Carbon nanotubes (SWCNTs)

Human alveolar epithelial cells (A549)

• Enhances Interleukin-8 (IL-8) expression in the presence of serum

• Induces changes in IL-8 expression

Basak et al. [120]

Multi-walled carbon nanotubes (MWCNTs) and TiO₂ nanobelts (TiO₂-NB)

Human colorectal adenocarcinoma cells

• Cytotoxicity

Patlolla et al. [121]

Multi-walled carbon nanotubes (MWCNTs)

Normal human dermal fibroblast cells (NHDF)

• Dose-dependent toxicity

• Massive loss of cell viability through DNA damage

• Cell death

Dahm et al. [122]

Carbon nanotubes and nanofibers (CNT/F)

Sputum samples

Scanning electron microscopy (SEM)

• Industrial workers are exposed to the toxic effect of carbon nanotubes at the workplace

Fatkhutdinova et al. [123]

Multi-walled carbon nanotubes (MWCNTs)

Blood and sputum samples from workers

• Induction of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β)

• Induction of KL-6 (a serological biomarker for interstitial lung disease)

• Accumulation of inflammatory and fibrotic biomarkers in biofluids of workers manufacturing MWCNTs

Zhao et al. [124]

Multi-walled carbon nanotubes (MWCNTs)

i.e., three commercially available MWCNTs, namely XFM4, XFM22, and XFM34 (diameters XFM4 < XFM22 < XFM34)

Human umbilical vein endothelial cells (HUVECs)

• XFM4 induced a significantly higher level of cytotoxicity than XFM22, and XFM34

• HUVECs internalized more XFM4

• XFM4 induces cytokine release, monocyte adhesion, and intracellular reactive oxygen species level

• XFM4 exposure reduces the expression of autophagic genes autophagy-related 7 (ATG7), autophagy-related 12 (ATG12), and beclin 1 (BECN1)

• Causes autophagy dysfunction and endoplasmic reticulum stress

Öner et al. [125]

Multi-walled carbon nanotubes (MWCNTs) and Single-walled carbon nanotubes (SWCNTs)

Human bronchial epithelial cells (16HBE)

• MWCNTs induce a single hypomethylation at a CpG site and gene promoter region

• No change in DNA methylation after the recovery period for MWCNTs

• SWCNTs or amosite induce hypermethylation at CpG sites after sub-chronic exposure

Luanpitpong et al. [126]

Carbon nanotubes (CNT)

Non-tumorigenic human lung epithelial cells

• Induces Cancer Stem-like cells (CSC) in lung epithelial cells

• Induces specific stem cell surface markers CD24 low and CD133 high that are associated with SWCNT-induced CSC formation and tumorigenesis

Shvedova et al. [127]

Carbon nanotubes (CNT)—Multi-walled carbon nanotubes (MWCNTs)

Air Sample

Peripheral whole blood

• Causes significant changes in the non-coding RNAs (ncRNA) and coding messenger RNAs (mRNA) expression profiles

• Cell cycle regulation/progression/control

• Apoptosis and proliferation

• Potential to trigger pulmonary and cardiovascular effects

• Potential to induce carcinogenic outcomes in humans

Domenech et al. [128]

Carbon-based nanoparticles: Graphene oxide (GO), Graphene nanoplatelets (GNPs)

Human colorectal adenocarcinomas (Caco-2, ATCC HTB-37)

• No oxidative damage induction was detected, either by the DCFH-DA assay or the FPG enzyme in the comet assay

• Both GO and GNPs induce DNA breaks

• Induces weak anti-inflammatory response

Wang et al. [129]

Single-walled carbon nanotubes (SWCNT) and multi-walled carbon nanotubes (MWCNTs)

Primary human Small Airway epithelial Cells (SAECs)

• Increases cell proliferation

• Induces anchorage-independent growth

• Causes cell invasion and angiogenesis

Mukherjee et al. [130]

Graphene oxide (GO)

human bronchial epithelium (BEAS-2B) cells

• Causes mitochondrial dysfunction after a 48-h exposure

• Causes engagement of apoptosis pathways after longer exposure periods (i.e., 28 days)

• Causes down regulation of genes belonging to the inhibitor of apoptosis protein (IAP) family

Pérez et al. [131]

Reduced graphene oxide (rGO)

Human airway epithelial (BEAS-2B) cells

• Medium-term rGO exposure does not have significant effects on the DNA methylation patterns of human lung epithelial cells

Xu et al. [132]

Single-walled carbon nanotubes (SWCNT)

Pulmonary surfactant monolayer (PSM)

• Inhalation toxicity of SWCNTs is largely affected by their lengths

• Short SWCNTs increases inflammatory response

• Longer SWCNTs causes severe lipid depletion and PSM-rigidifying effect

Gasser et al. [133]

Multi-walled carbon nanotubes (MWCNTs)

Human monocyte derived macrophages (MDM) monocultures

A sophisticated in vitro model of the human epithelial airway barrier

• Increases reactive oxygen species levels

• Decreases intracellular glutathione depletion in MDM

• Decreases the release of Tumour necrosis factor alpha (TNF-Î ±)

• Induces apoptosis

• Increases the release of the release of Interleukin-8 (IL-8)

Di Cristo et al. [134]

Graphene Oxide (GO)

EpiAirway™ tissues (AIR-100, PE6-5), a 3D mucociliary tissue model of the primary human bronchial epithelium

• Elicits proinflammatory response after 2 weeks exposure

• Causes moderate barrier impairment

• Induces autophagosome accumulation (resulting from blockade of autophagy flux)

• Prolonged exposures increase the risk of pulmonary infections and/or lung diseases

Chortarea et al. [135]

Carbon nanotubes (CNTs)

Human (alveolar) epithelial A549 cell line with human monocyte-derived dendritic cells (MDDCs) and macrophages (MDMs)

• Repeated exposures to lung cell cultures at the Air–Liquid Interface, elicit a limited biological impact over a three-day period

Lee et al. [26]

Graphene oxide (GO)

Workplace air samples

• Minimum release of graphene or other particles during manufacturing based on real-time aerosol monitoring

• Negligible exposure to graphene based on personal and area sampling for the Total Suspended Particles (TSP) and elemental carbon (EC)

Both Inorganic-based and Carbon-based Nanoparticles

Phuyal et al. [21]

Titanium dioxide (TiO₂) and multi-walled carbon nanotubes (MWCNTs)

Human bronchial epithelial (HBEC-3KT) cell line

• Low cytotoxicity in short-term tests

• Cell proliferation affected in long-term exposure

Shalini et al. [22]

Zinc oxide (ZnO) and nanorods

Human peripheral blood lymphocytes (HPBL)

• Genotoxicity in smaller ZnO NPs

• Cytotoxic effect in larger microparticles and microrods

• Higher level of oxidative potential and reactive oxygen species generation capacity in ZnO NPs and nanorods

Simon-Deckers et al. [23]

Aluminium oxide (Al₂O₃), Titanium dioxide – (TiO₂), Multi-walled carbon nanotubes (MWCNTs)

A549 human type II lung epithelium cell line

• Carbon nanotubes are more toxic than metal oxide NPs

• Both nanotubes and NPs rapidly enter into cells, and distribute in the cytoplasm and intracellular vesicles

Inorganic-based and Polymer Nanoparticles

Setyawati et al. [24]

Titanium dioxide (TiO₂), Terbium-doped gadolinium oxide (Tb-Gd₂O₃), and Poly (lactic-co-glycolic acid) (PLGA)

Human neonatal foreskin fibroblast cell line (BJ)

TiO₂ and Tb-Gd₂O₃:

• Dose-dependent cytotoxicity

• Promotes genotoxicity via DNA damage

PLGA nanoparticles:

• Did not induce significant cytotoxic or genotoxic effects on BJ

Polymer Nanoparticles

Nishu et al. [25]., 2020

Poly lactic-co-glycolic acid (PLGA)

Nitrosomonas europaea KCTC 12270 bacterium

Nitrospira moscoviensis bacterium

• Reduce nitrification in both cultures of nitrifying strains and in microbial communities in soil samples