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.
Highlights
Engineered nanomaterials encompass a large variety of inorganic and organic chemicals
Compared to the manufacturer’s specification of primary particle size (PPS), an increase in particle size of only 40–60% was observed when the test materials were suspended in protein-free F-12K medium, Krebs-Ringer phosphate glucose (KRPG) buffer, or 0.9% NaCl solution
The dispersed sizes of the respective test materials were nearly identical between these three protein-free media, indicating strong stabilization of all colloidal amorphous SiO2 by negative charge
Summary
Engineered nanomaterials encompass a large variety of inorganic and organic chemicals. While an increasing number of scientific publications address safety assessments of engineered nanomaterials [3,4,5,6,7], it is widely acknowledged that toxicity testing to meet full regulatory information requirements, e.g., in accordance with Regulation (EC) No 1907/2006 on the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH [8]), for every variant of a given nanomaterial would lead to an insurmountable amount of testing [9] This would further stand in contradiction to the ethical and legal requirement to replace, reduce, and refine animal testing (3Rs principle) [10,11]. A few of the numerous published in vitro studies investigating the cellular effects of nanomaterials were aimed at predicting in vivo toxicity potential [1,6,7,19,20,21,22]
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