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Table 3 Summary of the test results obtained for 13 nanomaterials and micron-scale ZnO in rat short-term inhalation studies

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

Test material Target con-centrations [mg/m3] NOAEC (mg/m3) Findings in the BALF Pathological and histological findings Reversibility of effects
Coated nano-TiO2 (T-Lite SF™) 0.5, 2.0, 10.0 0.5 Increased total cell counts, and PMN neutrophils, monocytes, total protein, GGT, LDH, ALP and NAG (cytokines not measured) Lung: pigment-loaded alveolar macrophages and slight diffuse histiocytosis Slight increases in BALF parameters remaining
Micron-scale ZnO 12.5 n.a. Increased total cell counts and PMN neutrophils, lymphocytes, monocytes, total protein, GGT, LDH, ALP and NAG. Many mediators increased; above 10-fold as compared to respective control values: clusterin; CRP; MCP-1; MCP-3; MDC; MPO; OPN. (Monocyte data not shown in Additional file 1: Table S1) Nasal cavity: severe multifocal necrosis of olfactory epithelia Lung: Increased absolute (+27%) and relative lung (+34%) weight, bronchoalveolar hyperplasia, histiocytosis, granulocytic infiltration Mediastinal lymph nodes: lympho-reticulo-cellular hyperplasia Slight to moderate histiocytosis in the lung and irregularities of olfactory epithelium remaining
Coated nano- ZnO (NM-111) 0.5, 2.5, 12.5 0.5 Increased total cell counts and PMN neutrophils, lymphocyte, monocyte, total protein, GGT, LDH, ALP and NAG. Many mediators increased; above 10-fold at highest concentration as compared to respective control values: CINC-1; clusterin; cystatin C; GCP-2; MCP-1; M-CSF; MDC; MPO; OPN Nasal cavity: moderate multifocal necrosis of olfactory epithelia Lung: histiocytosis, granulocytic infiltration Mediastinal lymph nodes: lympho-reticulo-cellular hyperplasia Moderate histiocytosis in the lung and irregularities of olfactory epithelium remaining
SiO2.naked 0.5; 2.5; 10.0; 50.0 2.5 Slightly increased PMN neutrophils and lymphocytes Slightly increased neutrophil counts in blood after the end of exposure (data not shown) Respiratory tract: Multifocal macrophage aggregates; Exacerbation towards a slight multifocal inflammation after 3 weeks (data not shown) Exacerbation towards a slight multifocal pulmonary inflammation
SiO2.acrylate 0.5; 2.0; 10.0 local effects: ≥ 10; systemic effects: 0.5 No adverse findings Respiratory tract: no adverse effects, Spleen: increased weight (+ 25%) without histological correlate; particles and high numbers of thrombocytes in the spleen, detected by TEM Full reversibility of splenetic effects; no pulmonary effects at any time point
SiO2.PEG 2.0; 10.0; 50.0 ≥ 50 No adverse findings No adverse findings n.a.
SiO2.phosphate 2.0; 10.0; 50.0 ≥ 50 No adverse findings No adverse findings n.a.
SiO2.amino 2.0; 10.0; 50.0 ≥ 50 No adverse findings No adverse findings n.a.
Nano-BaSO4 (NM-220) 2.0; 10.0; 50.0 ≥ 50 No adverse findings No adverse findings n.a.
Nano-ZrO2 0.5, 2.5, 10.0 ≥ 10 No adverse findings No adverse findings n.a.
ZrO2.TODA 2.0; 10.0; 50.0 ≥ 50 No adverse findings No adverse findings n.a.
ZrO2.acrylate 2.0; 10.0; 50.0 ≥ 50 No adverse findings No adverse findings n.a.
Nano-CeO2 0.5, 2.5, 10.0 < 0.5 Changes of all cytological and biochemical parameters in BALF; increased levels of Changes of CINC-1, IFNγ, IL-1α, MCP-1, M-CSF, in BALF and lung tissue Lung: Particles in macrophages (recovery group: additionally mild histiocytosis) Partial regression of BALF effects; mild diffuse or multifocal alveolar histiocytosis remaining
Al-doped nano- CeO2 0.5, 2.0 10.0 < 0.5 Changes of all cytological and biochemical parameters in BALF, increased MCP-1 and CINC-1 in BALF, increased IL1-α in lung tissue Lung: single or aggregated particle-loaded macrophages Partial regression of BALF effects; particle-loaded alveolar macrophages remaining
  1. n.a.: not applicable.