Table 1.
In vivo studies of AgNP exposures by the oral route
| Reference | Material (size) | Coating | Dose/endpoint | Species | Effects | Distribution |
|---|---|---|---|---|---|---|
| Mammalian, rodent | ||||||
| Bhol (2007) | Ag (NR) | 5.7% PVA | 0.4–4–40 mg/kg, recurring, 5 d | Rat (SD) | High dose: ↓ inflammation in colitis model | NR |
| Cha (2008) | Ag (13 nm) | none | 2.5 g one dose (150 g/kg)/3 d | Mouse (BALB/c) | Localised lymphocyte infiltration; gene alterations in apoptosis, inflammation | NR |
| Hadrup (2012) | Ag (14nm) | PVP | 2.25–9 mg/kg recurring, 28 d | Rat (Wistar) | No toxicological effects | NR |
| Jeong (2010) | Ag (60 nm) | 0.5% CMC | 30–300–1,000 mg/kg recurring, 28 d | Rat (SD) | Luminal and surface intestinal particle accumulation; ileal and colonic lamina propria and villus tips; increased mucus discharge into lumen from colon | NR |
| Kim (2010) | Ag (56 nm) | 0.5% CMC | 30–125–500 mg/kg recurring; 90 d | Rat (F344) | NOAEL: 30 mg/kg At 125 mg/kg liver effects: ↑alk phos and cholesterol; biliary hyperplasia | Kidney > Liver > Lung > Testes >> Brain >> Blood; In intestinal wall in male, not female; Females had higher kidney levels |
| Kim (2009) | Ag (60 nm) | 0.5% CMC | 30–300–1,000 mg/kg recurring; 90 d | Rat (F344) | Not assessed (distribution-focused) | Confirmed renal retention in females > males |
| Kim (2008) | Ag (60 nm) | 0.5% CMC | 30–300–1,000 mg/kg recurring; 28 d | Rat (SD) | LOAEL: 300 mg/kg based on ↑ alk phos, cholesterol; no genetic toxity as measured by micronucleus test on bone marrow; ↑RBC, Hgb, Hct, ↓ aPTT | Stomach > kidney > liver > lung; kidney accumulation female > male |
| Loeschner (2011) | Ag (14 nm) | PVP | 12.6 mg/kg recurring; 28 d | Rat (Wistar-Hannover-Galas) | Not assessed (distribution-focused study) | Small intestine >> stomach > kidney > liver >> lung; same tissue distribution as AgOAc but lower amount (by 40–50%) and higher fecal excretion (63% of daily dose); lamina propria and macrophage lysosomes’ |
| Park (2011) | Ag (7.9 nm) | Citrate | 1, 10 mg/kg, one dose, 24 hrs | Rat (SD) | Not assessed (distribution and bioavailablity-focused study) | Feces >>> Liver > Lung >kidney; evidence of biliary excretion; bioavailability of 1.2% (1 mg/kg) to 4.2% (10 mg/kg) |
| Park (2010) | Ag (22, 42, 71 and 323 nm) | Citrate | 0.25, 0.5, 1 mg/kg recurring, 14 and 28 d | Mouse | Dose-dependent ↑ inflammatory cytokines in blood; elevated B cells and IgE | Absorption inversely proportional to size, highest size not detected; Brain/liver/kidney/testis all at low levels |
| Mammalian, non-rodent | ||||||
| Ahmadi (2011a) | Ag | NR | 5–10–15 ppm feed recurring, 42 d | Chicken | None significant | Muscle > spleen > liver > kidney > feces |
| Ahmadi and Rahimi (2011b) | Ag | NR | 4–8–12 ppm water recurring; 42 d | Chicken | ↓ body wt, feed intake | Muscle > liver > feces |
| Ahmadi (2010) | Ag (14 nm) | NR | 5–15–25 ppm water recurring; 42 d | Chicken | Decreased lymphoid organ (bursa) weight | NR |
| Ahmadi (2009, 2009) | Ag (14 nm) | NR | 300–600–900 ppm water recurring; 56 d | Chicken (broilers) | None significant | NR |
| Fondevila (2009) | Ag (60–100 nm) | Sepiolite | 20–40 mg/kg (ppm) feed recurring; 35 d | Pigs | ↑ growth rate; ↓ coliforms | None in muscle, low in liver (2%) |