Table 2.
In vivo studies of metal NP other than Ag by the oral exposure route
| Reference | Material (size) | Coating | Dose/duration | Species | Effects | Distribution |
|---|---|---|---|---|---|---|
| Hillyer and Albrecht (2001) | Au (4, 10, 28, and 58 nm) | None/malto dextrin | 200 ug/ml in water; 7 d | Mouse (BALB/c) | Persorption through extruding (dying) ileal enterocytes | 58 nm: very low in all tissues; 28 nm: Intestine >> Stomach >> Spln >> Kidney/Liv/Heart; 10 nm: Intest/Kid/Stom > Lung/Hrt/Spleen>Liver/Brain; 4 nm: Kidney > Intest > Stom/Spln/Liv/Lung > Heart |
| Zhang et al. (2010c) | Au (13.5 nm) | None/water | 137.5–2,200 ug/kg; 14–28 d | Mouse (not specified) | ↓ body weight ; enlarged spleen at high dose; increased red blood cells at high dose | NR |
| Dhar et al. (2010) | Au (14 nm) | 0.02% gellan-gum stabilised | 75–150–300 ppm (mg/kg); 28 d | Rat (Wistar) | No alterations (body wt, hematology/clinical chemistry, histology, urinalysis, organ wts) | NR |
| Bu et al. (2010) | TiO2 (< 50 nm); mixture of anatase and rutile (% not specified) | Water | 160–400–1,000 mg/kg for 14 d | Rat (Wistar) | Dose-dependent ↑ liver (AST) and muscle (CK) enzymes; no histological changes; altered urinary metabolites at 1,000 g/kg | NR |
| Cui et al. (2011) | TiO2 (5 nm, anatase) | Hydroxypropyl-methylcellulose (HPMC) | 5–10–50 mg/kg; for 60 d | Mouse (CD-1) | ↑ inflammation-associated genes (TLR 2, TLR4, TNFa, NFkB, IL-2) | Only liver assessed (dose-dependent accumulation) |
| Duan et al. (2009) | TiO2 (5 nm as prepared: anatase) | HPMC | 62.5–125–250 mg/kg; for 30 d | Mouse (CD-1) | ↓ body wt, ↑ wt spleen, liver, kidney, thymus; hematological alterations mid-dose (125) | NR |
| Gui et al. (2011) | TiO2 (5–6 nm, as prepared; 294 nm hydrodynamic diameter with HPMC: anatase) | HPMC | 2.5–5–10 mg/kg; 90 d | Mouse (CD-1) | ↑ kidney weight; variable ↑ inflamm cytokines, variable ↑ renal biochemical parameters | Only kidney assessed (dose-dependent accumulation) |
| Trouiller et al. (2009) | TiO2 (P25: 25 nm; 25% rutile, 75% anatase; 160 nm as dosed) | In drinking water | 60–100 mg/kg; 5 d | Mouse C57BL/6 transgenic | DNA deletions, strand breaks, oxidative damage | NR |
| Wang et al. (2007) | TiO2 (25–80–155 nm; crystal composition not reported) | HPMC | 5,000 mg/kg; single dose; 24 hrs | Mouse (CD-ICR) | Minor ↑ liver and kidney enzymes in females for 25 nm | Liver >> lung > kidney > spleen > brain |
| Warheit et al. (2007) | TiO2 (140 nm as dosed; 80% anatase, 20% rutile) | Water | 175–550–1,750–5,000 mg/kg; single dose | Rat | Grey-coloured feces in high doses, no adverse effects | NR |
| Zhang et al. (2010a) | TiO2 (50–120 nm); and same sizes in combination with PbAC; crystal composition not reported | Phosphate buffered saline | 500, 5,000 mg/kg;7 d | Mouse (Kun Ming) | Synergistic (PbAC and TiO2) elevation in ROS in liver; hepatic necrosis in TiO2-PbAc groups | Liver>kidney>>brain (these were the only tissues evaluated) |
| Moulari (2008) | SiO2 (140 nm as dosed) | Coupled to 5-aminosalicylate (active drug) | Not defined (5-ASA conjugate up to 100 mg/kg) × 6 d | Mouse (BALB/c) | TNBS-induced colitis model; decreased effective dose for anti-inflammatory effects of 5-aminosalicylic acid in a colitis model | Active drug accumulated in inflamed tissues; other tissue distributions not measured |
| Chen (2006) | Cu (23.5 nm) | Hydroxypropyl-methylcellulose | 108–1,080 mg/kg; 48 h | Mouse (CD-ICR) | Renal tubular necrosis and pigmentary nephrosis; splenic atrophy; ↑ bile acids; LD50 (nanoCu): 413 mg/kg; LD50 (microCu): > 5,000 mg/kg; LD50 (ionicCu): 110 mg/kg | NR |
| Han (2010, 2011) | Cu-loaded chitosan (121.9 nm) | 0.9% saline | 80–160 mg/kg; 21 d | Rat (SD) | ↓ pathogenic cecal microbes, ↑ beneficial cecal microbes, ↑ digestive enzyme secretion | NR |
| Loginova (2012) | CdSe/CdS/CdZnS/ZnS quantum dots | Functionalised: with MPA, poly T, or poly T-APS (silica) | 200–290 pmol; single dose | Mouse (nude and CD-1) | No adverse effects | Detected only in GI tract; polyT-APS (silica) protected QDs from degradation |