Biodissolution and cellular response to MoO₃nanoribbons and a new framework for early hazard screening for 2D materials

Abstract

Two-dimensional (2D) materials are a broad class of synthetic ultra-thin sheet-like solids whose rapid pace of development motivates systematic study of their biological effects and safe design. A challenge for this effort is the large number of new materials and their chemical diversity. Recent work suggests that many 2D materials will be thermodynamically unstable and thus non-persistent in biological environments. Such information could inform and accelerate safety assessment, but experimental data to confirm the thermodynamic predictions is lacking. Here we propose a framework for early hazard screening of nanosheet materials based on biodissolution studies in reactive media, specially chosen for each material to match chemically feasible degradation pathways. Simple dissolution and in vitro tests allow grouping of nanosheet materials into four classes: A, potentially biopersistent; B: slowly degradable (>24–48 hours); C, biosoluble with potentially hazardous degradation products; and D, biosoluble with low-hazard degradation products. The proposed framework is demonstrated through an experimental case study on MoO3 nanoribbons, which have a dual 2D / 1D morphology and have been reported to be stable in aqueous stock solutions. The nanoribbons are shown to undergo rapid dissolution in biological simulant fluids and in cell culture, where they elicit no adverse responses up to 100μg ml−1 dose. These results place MoO3 nanoribbons in Class D, and assigns them a low priority for further nanotoxicology testing. We anticipate use of this framework could accelerate the risk assessment for the large set of new powdered 2D nanosheet materials, and promote their safe design and commercialization.

Chemical and Colloidal Dynamics of MnO2 Nanosheets in Biological Media Relevant for Nanosafety Assessment

“…Overall these results provide important insight for evaluating and managing potential environmental and human health risks of MnO 2 nanosheets. First, the results presented here are sufficient to apply the recently proposed human inhalation hazard screening framework for 2D materials [20] to the case of MnO 2 . This framework uses in vitro dissolution studies in reactive simulants to classify 2D materials into one of four categories for rationale hazard assessment and prioritization.…”

“…In the case of MnO 2 nanosheets, dissolution in environmental or biological systems can release potentially toxic ions including Mn 2+ , and it may be unclear whether toxicity is associated with the as-produced nanosheet or soluble dissolution products, [18] as described previously for silver nanoparticles. [62][63][64] The biodissolution of MnO 2 and its classification in the 2D material hazard screening framework [20] presents an interesting case study. MnO 2 is reported to be highly insoluble in water, [65] but capable of reductive dissolution in the presence of electron donors to release Mn 2+ ions accompanied by material degradation.…”

“…This framework uses in vitro dissolution studies in reactive simulants to classify 2D materials into one of four categories for rationale hazard assessment and prioritization. While oxidative and hydrolytic degradation routes are common, [20,94] MnO 2 is one of the few 2D materials proposed to follow a reductive degradation route, [18] and the first reductive case study in the Gray et al framework. [20] Human exposure to MnO 2 nanosheets in the form of aerosols or dry powders is a primary concern in occupational settings.…”

“…To address this challenge, an early hazard screening framework has been recently proposed for 2D materials. [20] The screening method uses simple biodissolution kinetic studies in reactive media specially chosen for each material to match chemically feasible degradation pathways, either oxidative, reductive, or nonredox. Reactive dissolution and in vitro toxicity tests on the nanosheets and their degradation products allow grouping of materials into four classes: A, potentially biopersistent; B, slowly degradable (>24-48 h); C, biosoluble with potentially hazardous degradation products; and D, biosoluble with low-hazard degradation products.…”

“…Reactive dissolution and in vitro toxicity tests on the nanosheets and their degradation products allow grouping of materials into four classes: A, potentially biopersistent; B, slowly degradable (>24-48 h); C, biosoluble with potentially hazardous degradation products; and D, biosoluble with low-hazard degradation products. [20] Performing this classification can accelerate hazard identification and safety assessment by: i) prioritizing a subset of persistent materials (Class A,B) for more detailed toxicity testing on the specific nanomaterial form in question, ii) identifying materials that are less likely to pose important health risks (Class D) and iii) finding a set of materials (Class C) for which the hazard assessment can avoid extensive nanotoxicity testing and instead use existing data on the chemical toxicity of soluble degradation products. The present article focuses on the biodissolution of manganese dioxide (MnO 2 ) nanosheets as a new case study in the development and validation of the framework.…”