Nanoparticle rank for toxicity Cell line(s) Dose and time Comments References Cu > Zn > Co > Sb > Ag > Ni > Fe > Zr > Al2 O3 > TiO2 > CeO, low toxicity for W Two human pulmonary cell lines (A549 and THP-1) 0.1–3300 MTT assay on THP-1 cell line exposed to NP for 24 h most sensitive experimental design Lanone et al. [64 ] ZnO > CeO2 /TiO2 BEAS-2B 6.125–50 μ g/mL, 1–6 h ZnO comparatively more toxic than TiO2 or CeO2 due to particle dissolution to Zn2+ George et al. [65 ] ZnO > CeO2 /TiO2 BEAS-2B and RAW264.7 macrophages 10–50 μ g/mL, 1–24 h ZnO dissolution in endosomes CeO2 suppressed ROS production and TiO2 did not elicit protective or adverse effects Xia et al. [66 ] ZnO > Fe2 O3 > TiO2 /CeO2 Human mesothelioma and rodent fibroblast cell line 30 μ g/mL, 3–6 days Human MSTO cells highly sensitive to Fe2 O3 Brunner et al. [67 ] ZnO > Fe > SiO2 L2 rat epithelial cells and rat primary alveolar macrophages and cocultures 0.0052–520 mg/cm2 , 1–48 h In vivo and in vitro measurements demonstrated little correlationSayes et al. [68 ] ZnO > TiO2 , Fe3 O4, Al2 O3 ,and CrO3 Neuro-2A cell line 10–200 μ g/mL, 2–72 h ZnO was more toxic compared to other NPs Jeng and Swanson [69 ] CdCl2 > CdSO4 > ZnSO4 > ZnO > CuSO4 > ZnCl2 > V2 O5 > CuCl2 > NiSO4 > NiCl2 > Fe2 (SO4 )3 > CrCl2 > VCl2 > CrK(SO4 )2 > FeCl2 A549 0.005–5 mM, 2–48 h RLE-6TN rat epithelia cells more sensitive than A549 cells Riley et al. [70 ] Ag > Fe2 O3 > Al2 O3 > ZrO2 > Si3 N4 > TiO2 in RAW264.7 and ZrO2 >Al2 O3 /Fe2 O3 /Si3 N4 /Ag > TiO2 in THB-1 and A549 Murine alveolar macrophage (RAW264.7), human macrophage (THB-1), and human epithelial A549 5 μ g/mL, 48 h THB-1 and A549 cells more sensitive than RAW264.7 and no correlation between specific surface area or NP morphology and toxicity Soto et al. [71 , 72 ] Ag > MoO3 > Al/Fe3 O4 /TiO2 Rat cell line (BRL 3A) 5–25 μ g/mL, 24 h Ag produces toxicity through oxidative stress Hussain et al. [73 ] Ag > Mn PC-12 cells 1–100 μ g/mL, 24 h Ag produced cell shrinkage and irregular membrane borders and Mn dose-dependently depleted dopamine Hussain et al. [74 ] Ag > NiO > TiO2 Murine macrophage cell line 5 μ g/mL, 48 h Nanoparticles characterized as aggregates, caution on Ag Soto et al. [75 ] Ag > MoO3 > Al Mouse spermatogonial stem cells 5–100 μ g/mL, 48 h Concentration-dependent toxicity for all NPs tested Braydich-Stolle et al. [76 ] Cu and Mn > Al PC-12 cells 10 μ g/mL, 24 h Txnrd1, Gpx1, Th, Maoa, Park2, and Snca genes expression altered Wang et al. [77 ] VOSO4 > TiO2 , SiO2 , NiO, Fe2 3 , CeO2 , and Al2 O3 BEAS-2B 1–100 μ g/mL, 24 h Manufactured pure oxides less toxic than natural particulate matter derived from soil dust and IL-6 secretion did not correlate with the generation of ROS in cell-free media Veranth et al. [78 ] Mn3 O4 > Co3 O4 > Fe2 O3 > TiO2 Lung epithelial cells A549 30 μ g/mL, 4 h Acellular ROS assay demonstrates catalytic conditions of NPs based on elemental composition Limbach et al. [79 ] Al > Al2 O3 Rat alveolar macrophages 25–250 μ g/mL, 24 h Phagocytosis hindered after exposure to Al NPs Wagner et al. [80 ] Nanoparticle(s) Animal Dose/route Result References Ag Rat 30–1000 mg/kg (subacute oral for 28 days) Dose-dependent effect on alkaline phosphatase and cholesterol. Twofold more accumulation of NP in kidneys of female than male Kim et al. [81 ] Ag Rat 1.73 × 104 /cm3 to 1.32 × 106 /cm3 (subacute inhalation, 6 h/day, 5 days/week for 4 weeks) Liver histopathological effect but no effect in hematology and biochemical parameters Ji et al. [82 ] Ag Zebrafish 5–100 μ g/mL (exposure, 72 h) Dose-dependent toxicity in embryos Asharani et al. [83 ] Ag Rat NP was implanted intramuscularly for 7, 14, 30, 90, and 180 days Inflammation Chen et al. [84 ] Ag Mice 100–1000 mg/kg (acute oral) Oxidative stress gene expression alterations Rahman et al. [85 ] Ag, Cu, and Al Mice and rat 30–50 mg/kg (intravenous/intraperitoneal) BBB penetration Sharma [86 ] Au Mice 2 × 105 PPB (oral for 7 days) NP uptake occurred in the small intestine by persorption through single, degrading enterocytes extruded from a villus Smaller particles cross the GI tract more readily
Hillyer and Albrecht [87 ] Cu Zebrafish 0.25–1.5 mg/L (exposure, 48 h) Biochemical, histopathological changes and alterations in gene expression Griffitt et al. [88 ] Cu Mice 108–1080 mg/kg (acute oral) NP-induced gravely toxicological effects and heavy injuries on kidney, liver, and spleen of treated mice Chen et al. [89 ] Fe2 O3 Rat 0.8–20 mg/kg (inhalation) Oxidative stress, inflammation, and pathology Zhu et al. [90 ] TiO2 Mice 5 g/kg (acute oral) Biochemical and histopathological effects Wang et al. [91 ] SiO2 magnetic-NPs Mice 25–100 mg/kg (intraperitoneal for 4 weeks) NPs were detected in brain indicating BBB penetration Kim et al. [92 ]
