Table 3.
In vivo literature associated with systemic endpoints after exposure to oxidic nickel nanoparticles. Studies are arranged by nanoparticle type, followed by exposure method.
| Study | Klimisch Score | Model | Dosing Regimen (Exposure Method) (Dose Range and Unit) (Duration/Frequency) (Follow-Up Time) |
Health Endpoint (Assay) |
|---|---|---|---|---|
| NiO Nanoparticles | ||||
| [72] | K3 A,B | Female white rats | Nose-only inhalation 1.0 mg/m3 4 h/d, 5 d 1 d 0.23 mg/m3 4 h/d, 5 d/w, 3, 6, 10 m 1 d |
Organ damage (histopathology of liver, kidney, brain, various functional and biochemical indices) |
| [70] | K3 A,B | Male F344 rats | Intratracheal instillation 2 mg/kg One time dose or 2–4 divided doses 3, 28, 91 d |
Organ damage (organ weight of liver, kidney, lung, spleen and brain; histopathology of liver, kidney, lungs, spleen, brain, and pulmonary-related lymph nodes) Hematological analysis (cell count, blood biochemistry) |
| [73] | K2 A | Male Wistar rats | Intratracheal instillation 0.015, 0.06, or 0.24 mg/kg 2 d/w, 6 w |
Liver damage (biomarkers of stress, liver weight, histopathology) |
| [27] | K2 A | Male Wistar rats | Oral gavage 500, 1000 mg/kg One time dose 14 days |
Clinical toxicology (food consumption, body weight, organ weight) Organ damage (various functional and biochemical indices, RBC and WBC count) |
| [34] | K2 C,D | Female Wistar rats | Oral gavage 5, 50, 300, 2000 mg/kg One time dose 14 d |
Organ damage (histopathology of brain, heart, liver, spleen and kidneys) Organ clearance (Ni content) Mortality |
| [35] | K2 A | Female Wistar rats | Oral gavage 125, 250, 500 mg/kg One time dose 24 h |
Organ damage (histopathology of liver, kidney, brain, various functional and biochemical indices) |
| [36] | K2 C,D | Male and female Wistar rats | Oral gavage 50, 100, 200 mg/kg 28 d, 7 d/w 24 h |
Clinical toxicology (food consumption, body weight, organ weight) Organ damage (histopathology of liver, kidney, brain, various functional and biochemical indices) |
| [48] | K3 A,E | Female rats | Intraperitoneal injection 250, 500 µg/rat 6 w, 3 d/w 24 h |
Organ damage (histopathology of liver, spleen, kidney, brain, various functional and biochemical indices) Organ clearance (Ni content of liver, spleen, kidney, brain) |
| [55] | K3 A,D,E | Male rats | Intraperitoneal injection 10, 25, 50 mg/kg 7 d 12 h |
Brain damage (Oxidative stress biomarkers including catalase activity, lipid peroxidation by MDA, Glutathione concentration, total antioxidant capacity; histopathology) |
| [56] | K3 A,B,E | Female rats | Intraperitoneal injection 500 µg/rat 6 w, 3 d/w |
Organ damage (histopathology of liver, spleen, kidney, brain, various functional and biochemical indices) Organ clearance (Ni content of liver, spleen, kidney, brain) Genotoxicity (DNA damage) |
| [40] | K3 A,B | Female C57BL/6N mice | Pharyngeal aspiration 50 µg/mouse One time dose 21 d |
Allergic response (OVA-specific immunoglobulin, gene expression) |
| Ni(OH)2 Nanoparticles | ||||
| [31] | K2 A | Male C57BL/6 mice | Whole body inhalation, 100, 150, 900 µg/m3, 1, 3, or 5 d, 5 h/d, 24 h |
Vascular function (carotid artery constriction and relaxation) |
| [46] | K3 A,B | Male ApoE−/− mice | Whole body inhalation, 100 µg/m3, 1 w or 5 m, 5 d/w, 5 h/d, 24 h |
Cardiovascular ROS/inflammation (ROS markers, mitochondrial DNA damage, BALF cell counts/protein, cytokine, chemokine) Systemic inflammation (liver SAP protein levels, cytokines/chemokines) Atherosclerosis (plaque formation in aorta, QT-PCR) |
| [50] | K3 A,B | Male C57BL/6 mice | Whole body inhalation 500 µg/m3 5 h 30 m and 12 h |
Hematopoietic damage (bone marrow EPC gene expression, EPC count, EPC chemotaxis, tube formation and proliferation, RT-PCR) |
| [51] | K3 A,B | C57BL/6 mice | Whole body inhalation, ∼1200 μg/m3, 2 d, 5 h/d, ∼700 μg/m3, 3 d, 5 h/d, ∼100 μg/m3, 5 d, 5 h/d, 24 h |
Endothelial progenitor cell effects (cell counts, cell function, cellular signaling pathways) |
| [52] | K3 A,B | C57BL/6 mice | Whole body inhalation, ∼500 μg/m3, 5 h, 0.5 and 12 h |
Endothelial progenitor cell effects (cell counts, cell function, cellular signaling pathways) Atherosclerosis (cellular signaling pathways) |
h: hour; d: day; w: week; m: month; A Not a guideline study. B Tested limited numbers of doses. C Deviated from OECD guidelines. D Lacked key details. E Non-physiological route of administration.