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Nanomaterials 2018, 8(3), 160; https://doi.org/10.3390/nano8030160

In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2

1
IBR R&D gGmbH Institute for Lung Health, Mendelstr. 11, 48149 Münster, Germany
2
Scientific Consultancy—Animal Welfare, 85579 Neubiberg, Germany
3
BASF SE, Human Biomonitoring and Industrial Hygiene, 67056 Ludwigshafen, Germany
4
BASF SE, Advanced Materials Research, 67056 Ludwigshafen, Germany
5
BASF SE, Experimental Toxicology and Ecology, 67056 Ludwigshafen, Germany
*
Author to whom correspondence should be addressed.
Received: 22 February 2018 / Revised: 7 March 2018 / Accepted: 9 March 2018 / Published: 13 March 2018
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Abstract

In vitro prediction of inflammatory lung effects of well-dispersed nanomaterials is challenging. Here, the in vitro effects of four colloidal amorphous SiO2 nanomaterials that differed only by their primary particle size (9, 15, 30, and 55 nm) were analyzed using the rat NR8383 alveolar macrophage (AM) assay. Data were compared to effects of single doses of 15 nm and 55 nm SiO2 intratracheally instilled in rat lungs. In vitro, all four elicited the release of concentration-dependent lactate dehydrogenase, β-glucuronidase, and tumor necrosis factor alpha, and the two smaller materials also released H2O2. All effects were size-dependent. Since the colloidal SiO2 remained well-dispersed in serum-free in vitro conditions, effective particle concentrations reaching the cells were estimated using different models. Evaluating the effective concentration–based in vitro effects using the Decision-making framework for the grouping and testing of nanomaterials, all four nanomaterials were assigned as “active.” This assignment and the size dependency of effects were consistent with the outcomes of intratracheal instillation studies and available short-term rat inhalation data for 15 nm SiO2. The study confirms the applicability of the NR8383 AM assay to assessing colloidal SiO2 but underlines the need to estimate and consider the effective concentration of such well-dispersed test materials. View Full-Text
Keywords: alveolar macrophage; short-term inhalation study (STIS); intratracheal instillation; in vitro cytotoxicity; 3R method; dosimetry; TNFα; nanomaterial grouping; regulatory hazard assessment alveolar macrophage; short-term inhalation study (STIS); intratracheal instillation; in vitro cytotoxicity; 3R method; dosimetry; TNFα; nanomaterial grouping; regulatory hazard assessment
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wiemann, M.; Sauer, U.G.; Vennemann, A.; Bäcker, S.; Keller, J.-G.; Ma-Hock, L.; Wohlleben, W.; Landsiedel, R. In Vitro and In Vivo Short-Term Pulmonary Toxicity of Differently Sized Colloidal Amorphous SiO2. Nanomaterials 2018, 8, 160.

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