A Method to Assess the Relevance of Nanomaterial Dissolution during Reactivity Testing

The reactivity of particle surfaces can be used as a criterion to group nanoforms (NFs) based on similar potential hazard. Since NFs may partially or completely dissolve over the duration of the assays, with the ions themselves inducing a response, reactivity assays commonly measure the additive reactivity of the particles and ions combined. Here, we determine the concentration of ions released over the course of particle testing, and determine the relative contributions of the released ions to the total reactivity measured. We differentiate three classes of reactivity, defined as being (A) dominated by particles, (B) additive of particles and ions, or (C) dominated by ions. We provide examples for each class by analyzing the NF reactivity of Fe2O3, ZnO, CuO, Ag using the ferric reduction ability of serum (FRAS) assay. Furthermore, another two reactivity tests were performed: Dichlorodihydrofluorescin diacetate (DCFH2-DA) assay and electron paramagnetic resonance (EPR) spectroscopy. We compare assays and demonstrate that the dose-response may be almost entirely assigned to ions in one assay (CuO in DCFH2-DA), but to particles in others (CuO in EPR and FRAS). When considering this data, we conclude that one cannot specify the contribution of ions to NF toxicity for a certain NF, but only for a certain NF in a specific assay, medium and dose. The extent of dissolution depends on the buffer used, particle concentration applied, and duration of exposure. This culminates in the DCFH2-DA, EPR, FRAS assays being performed under different ion-to-particle ratios, and differing in their sensitivity towards reactions induced by either ions or particles. If applied for grouping, read-across, or other concepts based on the similarity of partially soluble NFs, results on reactivity should only be compared if measured by the same assay, incubation time, and dose range.

[1]  P. Westerhoff,et al.  Ferric reducing reactivity assay with theoretical kinetic modeling uncovers electron transfer schemes of metallic-nanoparticle-mediated redox in water solutions , 2019, Environmental Science: Nano.

[2]  Antonio Marcomini,et al.  Grouping and Read-Across Approaches for Risk Assessment of Nanomaterials , 2015, International journal of environmental research and public health.

[3]  Kristie J. Koski,et al.  Biodissolution and Cellular Response to MoO3 Nanoribbons and a New Framework for Early Hazard Screening for 2D Materials. , 2018, Environmental science. Nano.

[4]  Thomas A. J. Kuhlbusch,et al.  Analytical methods to assess the oxidative potential of nanoparticles: a review , 2017 .

[5]  Reinhard Kreiling,et al.  A decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping). , 2015, Regulatory toxicology and pharmacology : RTP.

[6]  A. Punnoose,et al.  ZnO nanoparticle preparation route influences surface reactivity, dissolution and cytotoxicity. , 2018, Environmental science. Nano.

[7]  Wendel Wohlleben,et al.  Surface reactivity measurements as required for grouping and read-across: An advanced FRAS protocol , 2017 .

[8]  M. Vijver,et al.  Toxicity of different‐sized copper nano‐ and submicron particles and their shed copper ions to zebrafish embryos , 2014, Environmental toxicology and chemistry.

[9]  Dana Kühnel,et al.  Grouping concept for metal and metal oxide nanomaterials with regard to their ecotoxicological effects on algae, daphnids and fish embryos , 2018 .

[10]  Philip Demokritou,et al.  Screening for oxidative damage by engineered nanomaterials: a comparative evaluation of FRAS and DCFH , 2014, Journal of Nanoparticle Research.

[11]  J. Aghassi‐Hagmann.  Nanoenabled Products: Categories, Manufacture, and Applications , 2017 .

[12]  Lutz Mädler,et al.  Use of metal oxide nanoparticle band gap to develop a predictive paradigm for oxidative stress and acute pulmonary inflammation. , 2012, ACS nano.

[13]  Monika Herrchen,et al.  The nanoGRAVUR framework to group (nano)materials for their occupational, consumer, environmental risks based on a harmonized set of material properties, applied to 34 case studies. , 2019, Nanoscale.

[14]  Dhimiter Bello,et al.  Mapping the biological oxidative damage of engineered nanomaterials. , 2013, Small.

[15]  Susan Wijnhoven,et al.  Risk assessment frameworks for nanomaterials: Scope, link to regulations, applicability, and outline for future directions in view of needed increase in efficiency , 2018 .

[16]  G. Hendriks,et al.  High variability in toxicity of welding fume nanoparticles from stainless steel in lung cells and reporter cell lines: the role of particle reactivity and solubility , 2019, Nanotoxicology.

[17]  W J Stark,et al.  Industrial applications of nanoparticles. , 2015, Chemical Society reviews.