Abstract
Dissolution rates of nanomaterials can be decisive for acute in vivo toxicity (via the released ions) and for biopersistence (of the remaining particles). Continuous flow systems (CFSs) can screen for both aspects, but operational parameters need to be adjusted to the specific physiological compartment, including local metal ion saturation. CFSs have two adjustable parameters: the volume flow-rate and the initial particle loading. Here we explore the pulmonary lysosomal dissolution of nanomaterials containing the metals Al, Ba, Zn, Cu over a wide range of volume flow-rates in a single experiment. We identify the ratio of particle surface area (SA) per volume flow-rate (SA/V) as critical parameter that superimposes all dissolution rates of the same material. Three complementary benchmark materials—ZnO (quick dissolution), TiO2 (very slow dissolution), and BaSO4 (partial dissolution)—consistently identify the SA/V range of 0.01 to 0.03 h/cm as predictive for lysosomal pulmonary biodissolution. We then apply the identified method to compare against non-nanoforms of the same substances and test aluminosilicates. For BaSO4 and TiO2, we find high similarity of the dissolution rates of their respective nanoform and non-nanoform, governed by the local ion solubility limit at relevant SA/V ranges. For aluminosilicates, we find high similarity of the dissolution rates of two Kaolin nanoforms but significant dissimilarity against Bentonite despite the similar composition.
Highlights
With a steadily increasing demand for engineered nanomaterials (ENMs) for industrial applications, the ENM production volumes reported by industry are a significant share of the total particle production [1]
For CuO and ZnO local saturation at the solubility limit can occur, and for values of surface area (SA)/V above 0.1 h/cm, the dissolution rate of both materials drops below 100 ng/cm2/h, and rates corresponding to halftimes longer than two days are predicted
Ramping the flow-rate is a promising approach to expand the range of regular out-of-equilibrium flow-through dissolution to nearly five orders of magnitude of the decisive parameter SA/V, which is the ratio of surface area and volume flow
Summary
With a steadily increasing demand for engineered nanomaterials (ENMs) for industrial applications, the ENM production volumes reported by industry are a significant share of the total particle production [1]. The nanoform is described through chemical composition, surface properties, size, and shape [6] These properties are insufficient to forecast potential environmental and human health-related hazards and do not take into account the complex mechanism of pulmonary retention, clearance, and translocation that particles are exposed to upon inhalation [7,8,9,10]. The European Chemicals Agency (ECHA) as well as the Environmental Protection Agency (EPA) are prioritizing the dissolution rate as a key criterion for the assessment of the risk potential of nanomaterials [11]. This criterion can be used to compare different nanoforms of a substance. The decisive parameter in MMVF testing was the ratio SA/V of surface area per flow-rate, but this has not been explored yet for nanomaterials
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