Alternative test methods for (nano)materials hazards assessment: Challenges and recommendations for regulatory preparedness

Abstract The outstanding work performed by standardization organizations for guidelines to assess hazards, e.g., OECD (Organisation for Economic Co-operation and Development), is clearly visible by the currently available number and broad coverage, from aquatic to terrestrial organisms dealing with environmental relevant issues. Nevertheless, novel materials challenge the adequateness and fit-for-purpose of such standards, as the standards were developed to assess hazards of “conventional” chemical substances and not advanced materials (e.g. materials that may deliberately change behaviour). While standardization is a well-known process that requires extended time before reaching implementation stage, there is strong support from regulatory bodies for the development of New Approach Methodologies (NAMs) (e.g., updating of current guidelines, development of novel omics-, in vitro-, and in silico- tests including modelling and read-across) that meet regulatory preparedness (i.e. have considered issues important for regulatory testing). There are currently several NAMs available, complying with high quality standards and relevancy, which should be adopted. In the current review, we collected the available literature on NAMs to assess hazards of Nanomaterials (NMs), focusing on the terrestrial environment, and critically discuss the advantages, challenges and gaps. Tests were grouped into 1) Standard tests (OECD/ISO), 2) Standard tests (OECD/ISO) extensions: time course or prolonged exposures and/or multigenerational, and 3) Alternative tests, beyond current OECD/ISO: omics, biomarkers, in vitro, in silico and modelling. The goal is to provide guidance on the best practices and test designs focusing on the specificities of testing NMs, outlining recommendations and way forward.