NF | Model | Dose | Experimental design | Particles/Ions accumulation ** | Effects | Reference | |
---|---|---|---|---|---|---|---|
Local | Systemic | ||||||
SiO2 (NM-203) | Rats | 5, 10, or 20Â mg/bw* | 3-repeated exposure by oral gavage (sub-acute) | Not assessed | No histological changes of duodenum and colon; weak genotoxic effects in the colon | No histological changes of tissue samples from spleen, liver and kidney | [37] |
CuO (Plasma Chem, GmbH) | Rats | 1, 2, 4, 8, 16, and 32Â mg/kg bw | 5-repeated exposure by oral gavage (sub-acute) | Copper ions detected in liver, lung, kidneys, spleen, thymus, and mesenteric lymph node tissue | Histological changes in stomach where inflammation was observed | Alterations in the level of alkaline phosphatase (ALP) and aspartate aminotransferase (AST) liver enzymes; Histological changes in liver and bone marrow; Liver exhibited slight Kupffer cell hypertrophy/ hyperplasia and inflammation; Bone marrow changes included slight increased myeloid elements and decreased erythroid elements | [38] |
SiO2 (Levasil® 200; Levasil® 200 PEG treated; Levasil® 200 phosphate treated; Levasil® 200 amino treated) | Rats | 1000 mg/kg/bw | 28-repeated exposure by oral gavage (sub-acute) | Not assessed | No adverse effects for any of the tested silicas (histopathological examination) | No adverse effects for any of the tested silicas (clinical pathology, clinical chemistry, acute phase proteins and metabolome analysis) | [39] |
SiO2 (mesoporous silicas of two target sizes, 100 and 300Â nm) | Mice | 100 and 1000Â mg/kg/bw | 5-repeated exposure by oral gavage (sub-acute) | Silica particles detected in jejunum | No histological changes of small intestine; No intestinal inflammation | No histological changes of liver | [40] |
SiO2 (NM-203) | Rats | 2, 5, 10, 20 and 50Â mg/kg/bw* | 90-repeated exposure by oral gavage (sub-chronic) | Silicon ions detected in liver and spleen | No histological changes of small intestine | No alteration in AST, Alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine serum levels; No histological changes of spleen, adrenals, Kidneys and thyroid; Different alterations were reported in the liver (hepatocyte vacuolization/steatosis, intralobular lymphoid infiltration, enlarged sinusoids and congestion of sinusoids); Histomorphometrical alterations in spleen; Different alteration in the immunotoxicity markers in the blood | [36] |
SiO2 (NM-200) | Mice | 4.8Â mg/kg/bw* | 18Â months via drinking water (chronic) | Silicon ions detected in liver and kidney | Not assessed | Histomorphological alterations were identified in kidneys (vacuolization of tubular epithelial cells); Liver inflammation coupled to amyloidosis lesions | [41] |
SiO2 (NM-203) | Rats | 20Â mg/kg/bw | 1 and 5-repeated exposure by intravenous administration (acute and sub-acute) | Not assessed | Not assessed | Splenomegaly accompanied by inflammatory granulomas; Granulomas in liver parenchyma | [42] |
SiO2 (mesoporous silicas of 75Â nm) | Mice | 50-100-200Â mg/kg/bw | 14-repeated exposure by oral gavage (sub-acute) | Silica particles detected outside the intestinal tissue and in the cytoplasm; Silicon ions detected in heart, liver, spleen, kidney, colon and intestine | Infiltration of inflammatory cells in the intestines; Intestinal oxidative stress and colonic epithelial cell apoptosis; no sign of genotoxicity in intestine | Increase of ALP, ALT and AST serum levels; Infiltration of inflammatory cells in the spleen | [43] |
SiO2 (two colloidal silicas of 46 and 432 nm and mesoporous silicas of 466 nm) | Mice | 100–300 mg/kg/bw (colloidal silicas); 100 mg/kg/bw (mesoporous silicas) | Single dose by intravenous administration (acute) | Not assessed | Not assessed | Tissue injury of heart, lungs, kidney, liver and spleen | [44] |
SiO2 (NM-203) | Rats | 2, 5, 10, 20 and 50Â mg /kg/bw* | 90-repeated exposure by oral gavage (sub-chronic) | Not assessed | Not assessed | Weak genotoxic effect in the spleen | [45] |
SiO2 (NM-203) | Rats | 2, 5, 10, 20 and 50Â mg /kg/bw* | 90-repeated exposure by oral gavage (sub-chronic) | Not assessed | Not assessed | No genotoxic effects in reproductive system (male and female) | [46] |