A critical appraisal of existing concepts for the grouping of nanomaterials

Abstract

The grouping of substances serves to streamline testing for regulatory purposes. General grouping approaches for chemicals have been implemented in, e.g., the EU chemicals regulation. While specific regulatory frameworks for the grouping of nanomaterials are unavailable, this topic is addressed in different publications, and preliminary guidance is provided in the context of substance-related legislation or the occupational setting. The European Centre for Ecotoxicology and Toxicology of Chemicals Task Force on the Grouping of Nanomaterials reviewed available concepts for the grouping of nanomaterials for human health risk assessment. In their broad conceptual design, the evaluated approaches are consistent or complement each other. All go beyond the determination of mere structure-activity relationships and are founded on different aspects of the nanomaterial life cycle. These include the NM's material properties and biophysical interactions, specific types of use and exposure, uptake and kinetics, and possible early and apical biological effects. None of the evaluated grouping concepts fully take into account all of these aspects. Subsequent work of the Task Force will aim at combining the available concepts into a comprehensive 'multiple perspective' framework for the grouping of nanomaterials that will address all of the mentioned aspects of their life cycles.

Insights into possibilities for grouping and read-across for nanomaterials in EU chemicals legislation

“…There are multiple reviews of the state of the art for the grouping of NMs (Arts et al 2014(Arts et al , 2015ECHA 2016a). Arts et al (2014) focussed on human health aspects (specifically, inhalation), and proposed that the apical toxic effects of NMs are directed by intrinsic material properties and extrinsic properties (Arts et al 2015), that is, properties that depend on the surroundings.…”

“…Arts et al (2014) focussed on human health aspects (specifically, inhalation), and proposed that the apical toxic effects of NMs are directed by intrinsic material properties and extrinsic properties (Arts et al 2015), that is, properties that depend on the surroundings. However, neither the exact correlation(s) of properties and effects nor the interdependence of some material properties are yet established; thus, the grouping of NMs should not rely on intrinsic material properties alone.…”

“…However, scientifically based grouping and readacross methods have not yet been fully established or accepted for NMs, though several science-based approaches for grouping NMs have been suggested (e.g. Arts et al 2014;Arts et al 2015;ECHA 2016a;Hund-Rinke, Nickel, and K€ uhnel 2017). As a first step, ECHA has proposed guidance relevant to NMs for grouping and read-across within one substance registration (ECHA 2017b).…”

“…Grouping and read-across of NMs may be performed for various other purposes in addition to that of filling data gaps and use in weight-of-evidence approaches (Arts et al 2014;OECD 2016a), such as (a) supporting prioritization and selection of NMs for further testing; (b) enabling ranking of NMs according to selected endpoints; and (c) justifying waiving of specific tests for individual NMs. Establishing sound grouping concepts also improves the understanding of structure/propertyactivity relationships for NMs, and thus supports more targeted testing and risk assessment.…”

Prediction of Oral Absorption of Nanoparticles from Biorelevant Matrices Using a Combination of Physiologically Relevant In Vitro and Ex Vivo Models

“…This implies the need for more predictive models for the human situation, while taking into account the essentials of the 3R principle in replacing, reducing, and refining animal testing [40,41]. To that extent, the use of ex vivo human intestinal tissue segments has been suggested [8].…”