Table 5.
Study design
|
Test substance |
Coated nano-TiO 2 | SiO 2 .acrylate | Micron-scale ZnO; Coated nano-ZnO (NM-111) | Nano-CeO 2 ; Nano-ZrO 2 | SiO 2 .naked; BaSO 4 (NM-220); Al-doped nano-CeO 2 | SiO 2 .PEG; SiO 2 .phosphate; SiO 2 .amino; ZrO 2 .TODA; ZrO 2 .acrylate |
|---|---|---|---|---|---|---|
| Study element/part | ||||||
| Recovery period |
21 |
14 |
21 |
21 |
21 |
21 |
| Necropsy and histology of respiratory tract |
√a |
√b |
√b |
√b |
√c |
√a |
| Histology of brain |
n.d. |
√b |
√b |
√b |
n.d. |
√a |
| Cell proliferation and apoptosis |
n.d. |
n.d. |
√b |
√b |
n.d. |
n.d. |
| Electron microscopy |
n.d. |
√ a |
n.d. |
n.d. |
n.d. |
n.d. |
| BALF cytology, protein and enzyme activitiesd |
√ |
√ |
√ |
√ |
√ |
√ |
| BALF cytokines and chemokinesd |
n.d. |
M-CSF, TGF-β, MIP-2, MCP-1, IL-1α |
68 cytokines, chemokines and inflammation-relevant hormones and enzymese |
68 cytokines, chemokines and inflammation-relevant hormones and enzymese |
Clusterin; MCP-1; CINC-1/IL-8; M-CSF; OPN |
MCP-1; CINC-1 /IL-8; M-CSF; OPN |
| Cytokines and chemokines in lavaged lung tissued |
n.d. |
n.d. |
n.d. |
68 cytokines, chemokines and inflammation-relevant hormones and enzymese |
IL-1α TNF-α |
IL-1α TNF-α |
| Hematology according to OECD TG 412; c-reactive protein and haptoglobind |
n.d. |
√ |
√ |
√ |
√ |
√ |
| Organ burdena, f | √ | √ | √ | √ | √ | √ |
n.d.: not determined.
aFor these investigations, altogether 3 animals per concentration and time point were used.
bFor these investigations, altogether 6 animals per concentration and time point were used.
cFor this investigations, 3 animals per concentration and time point were used in the BaSO4 and Al-doped CeO2 test runs, whereas 6 animals per concentration and time point were used in the SiO2.naked test run.
dFor these investigations, altogether 5 animals per concentration and time point were used.
ec.f. Evaluation of bronchoalveolar lavage fluid (BALF) and lung tissue homogenates.
fFor all test materials, tissue contents of the respective main element were determined in the lung and lung-associated mediastinal lymph nodes. For coated nano-TiO2, BaSO4, Al-doped CeO2, nano- and micron-scale ZnO, additionally, organ burden of the extra-pulmonary organs was assessed.
Abbreviations: CINC-1/IL-8 cytokine-induced neutrophil chemoattractant-1, the rat homologue to IL-8, IL interleukin, M-CSF macrophage colony stimulating factor, MCP, monocyte chemoattractant protein, MIP macrophage inflammatory protein, OPN osteopontin, TNF-α tumor necrosis factor-α.