Evaluation of Toxicity Ranking for Metal Oxide Nanoparticles via an in Vitro Dosimetry Model

Abstract

It has been argued that in vitro toxicity testing of engineered nanoparticles (NPs) should consider delivered dose (i.e., NP mass settled per suspension volume) rather than relying exclusively on administered dose (initial NP mass concentration). Delivered dose calculations require quantification of NP sedimentation in tissue cell culture media, taking into consideration fundamental suspension properties. In this article, we calculate delivered dose using a first-principles "particles in a box" sedimentation model, which accounts for the particle size distribution, fractal dimension, and permeability of agglomerated NPs. The sedimentation model was evaluated against external and our own experimental sedimentation data for metal oxide NPs. We then utilized the model to construct delivered dose-response analysis for a library of metal oxide NPs (previously used for hazard ranking and prediction making) in different cell culture media. Hierarchical hazard ranking of the seven (out of 24) toxic metal oxide NPs in our library, using EC50 calculated on the basis of delivered dose, did not measurably differ from our ranking based on administered dose. In contrast, simplified sedimentation calculations based on the assumption of impermeable NP agglomerates of a single average size significantly underestimated the settled NPs' mass, resulting in misinterpretation of toxicity ranking. It is acknowledged that in vitro dose-response outcomes are likely to be shaped by complex toxicodynamics, which include NP/cellular association, triggering of dynamic cell response pathways involved in NP uptake, and multiple physicochemical parameters that influence NP sedimentation and internalization.

Reduction of pulmonary toxicity of metal oxide nanoparticles by phosphonate-based surface passivation

“…This dose range is equivalent to 0.5-6 mg/m 2 of MOx exposure in the mouse lung, assuming the alveolar epithelium surface area of 0.05 m 2 and a body weight of 25 g [38]. Assuming that the in vitro MOx dose is homogeneously distributed in cell culture media (100 μL/well, 96 well plate) and the percentages of MOx settlement are higher than 70% [39], the in vitro cell exposure dose would be 1.6-16 μg/mL. The in vivo dose used in this study is 2 mg/kg, which has previously been shown to be on the steep part of the dose response curve for MOx and relevant to the airborne levels of MOx in workplace [13].…”

Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines

“…The density of surface silanols can also be a determinant of electrostatic interaction of fumed SiNPs with membrane phospholipids (Zhang et al, 2012). Recent reports highlight the importance of characterizing nanoparticle interactions in liquid suspensions and their impact on in vitro dosimetry, along with determining sedimentation and diffusion rates of suspended nanoparticle agglomerates and nonagglomerated particles to improve estimates of dose delivered to cells (Cohen et al, 2013;DeLoid et al, 2014;Liu et al, 2015;Pal et al, 2015). Correction of the b potency estimates for the effective delivered dose of the SiNPs in the present study indicated a 64% (1.64Â) increase in deposited dose of SiNP (12 nm) relative to the other SiNPs.…”

Safe‐by‐Design Ligand‐Coated ZnO Nanocrystals Engineered by an Organometallic Approach: Unique Physicochemical Properties and Low Toxicity toward Lung Cells

“…[18] The resulting water-soluble ZnO NCs exhibited unprecedentedu ltralong-lived electron-hole separation (up to 2.2 ms) [18a] and, by taking advantage of the exceptional properties of ZnO NCs modifiedw ith ao ligoethylene glycol carboxylate shell, we created an anohybrid system for H 2 evolution under visible-light irradiation. [21] Following the statement of Cohen and co-workers: [22] "efforts are now mounting to ensure the development and application of safe-by-design engineered nanomaterials so as to avoid adverse environmental and humanh ealth impacts" and advancing the OSSOM method, herein we report on the synthesis of quantum-sized ZnO NCs coated by ad enselyp acked 2-(2-methoxyethoxy)acetate ligand shell as am odel system for in vitro cytotoxicity studies by cell metabolic activity assay (MTT) in normal( MRC-5) and cancer( A549) human lung cell lines. reported another variant of the organometallic approach for ZnO NC synthesis through the hydrolysis of R 2 Zn supported by substoichiometric quantities of zinc carboxylates Zn(O 2 CR') 2 or zinc phoshinatesZ n(O 2 PR' 2 ) 2 and their utility as ac omponent of ZnO/Cu nanocatalysts or antimicrobial polymer surfaces.…”