A decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping)

Abstract

The European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) 'Nano Task Force' proposes a Decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) that consists of 3 tiers to assign nanomaterials to 4 main groups, to perform sub-grouping within the main groups and to determine and refine specific information needs. The DF4nanoGrouping covers all relevant aspects of a nanomaterial's life cycle and biological pathways, i.e. intrinsic material and system-dependent properties, biopersistence, uptake and biodistribution, cellular and apical toxic effects. Use (including manufacture), release and route of exposure are applied as 'qualifiers' within the DF4nanoGrouping to determine if, e.g. nanomaterials cannot be released from a product matrix, which may justify the waiving of testing. The four main groups encompass (1) soluble nanomaterials, (2) biopersistent high aspect ratio nanomaterials, (3) passive nanomaterials, and (4) active nanomaterials. The DF4nanoGrouping aims to group nanomaterials by their specific mode-of-action that results in an apical toxic effect. This is eventually directed by a nanomaterial's intrinsic properties. However, since the exact correlation of intrinsic material properties and apical toxic effect is not yet established, the DF4nanoGrouping uses the 'functionality' of nanomaterials for grouping rather than relying on intrinsic material properties alone. Such functionalities include system-dependent material properties (such as dissolution rate in biologically relevant media), bio-physical interactions, in vitro effects and release and exposure. The DF4nanoGrouping is a hazard and risk assessment tool that applies modern toxicology and contributes to the sustainable development of nanotechnological products. It ensures that no studies are performed that do not provide crucial data and therefore saves animals and resources.

Frameworks and tools for risk assessment of manufactured nanomaterials

“…This has become a dynamic area of research and several frameworks for grouping and read-across of MNs have been proposed (Arts et al, 2015a, RIVM, 2015, ECHA, JRC and RIVM, 2016, Gebel et al, 2014, Walser and Studer, 2015. These approaches are still rather conceptual and are not based on sufficient understanding of the interdependencies among the intrinsic and extrinsic properties of MNs and their observed adverse biological effects .…”

“…These approaches are still rather conceptual and are not based on sufficient understanding of the interdependencies among the intrinsic and extrinsic properties of MNs and their observed adverse biological effects . They were developed from either human health (Arts et al, 2015a) or environmental (RIVM, 2015) perspective and therefore differ significantly in the hierarchy of investigated physicochemical properties. Schemes developed from an occupational perspective often use "morphology" as a key grouping criterion, which was motivated by the well-established concern of inhalation of fibrous materials.…”

“…• Strongly depends on data on physicochemical parameters of each nanoform, which are often unavailable • Requires high quality of the data for monitoring of physicochemical parameters during testing, which is difficult to ensure or derive from the published literature • Limited to read-across for hazard endpoints ECETOC decision analytical framework to facilitate the grouping of nanomaterials (DF4nanoGrouping) (Arts et al, 2015a) DF4nanoGrouping consists of 3 tiers to assign MNs to 4 main groups:…”

“…The released materials age under various environmental conditions. Thus, at each lifecycle stage there is a potential of exposure to MNs with different physicochemical properties , Oomen et al, 2014b, Arts et al, 2015b. A portfolio of physicochemical characterization techniques is required to understand the identity of the MNs reaching target organs and environmental species.…”

Assessing nanomaterial exposures in aquatic ecotoxicological testing: Framework and case studies based on dispersion and dissolution

“…However, it remains unclear if and when scientifically defensible consensus will be resolved. Further, it is unclear if categorization of ingredient ENMs that are constituents of NEPs are representative of, or relevant to, materials that may be released from NEPs and potentially transformed (e.g., composition, solubility, biopersistence, aspect ratio, chemical activity) in environmental matrices (Arts et al, 2015). Interim hazard assessment methods are needed since NEPs are rapidly entering commercial and other markets; investigators need to supply the best available knowledge on ENM toxicological exposure and hazard to facilitate current risk assessment decisions (Godwin et al, 2015;Hansen et al, 2014).…”