Particle and Fibre Toxicology

Table 5 Study design

From: Application of short-term inhalation studies to assess the inhalation toxicity of nanomaterials

Test substance	Coated nano-TiO₂	SiO₂.acrylate	Micron-scale ZnO; Coated nano-ZnO (NM-111)	Nano-CeO₂; Nano-ZrO₂	SiO₂.naked; BaSO₄(NM-220); Al-doped nano-CeO₂	SiO₂.PEG; SiO₂.phosphate; SiO₂.amino; ZrO₂.TODA; ZrO₂.acrylate
Study element/part	Coated nano-TiO₂	SiO₂.acrylate	Micron-scale ZnO; Coated nano-ZnO (NM-111)	Nano-CeO₂; Nano-ZrO₂	SiO₂.naked; BaSO₄(NM-220); Al-doped nano-CeO₂
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 activities^d	√	√	√	√	√	√
BALF cytokines and chemokines^d	n.d.	M-CSF, TGF-β, MIP-2, MCP-1, IL-1α	68 cytokines, chemokines and inflammation-relevant hormones and enzymes^e	68 cytokines, chemokines and inflammation-relevant hormones and enzymes^e	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 tissue^d	n.d.	n.d.	n.d.	68 cytokines, chemokines and inflammation-relevant hormones and enzymes^e	IL-1α TNF-α	IL-1α TNF-α
Hematology according to OECD TG 412; c-reactive protein and haptoglobin^d	n.d.	√	√	√	√	√
Organ burden^{a, 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.

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