A Weight of Evidence approach to classify nanomaterials according to the EU Classification, Labelling and Packaging Regulation criteria

Abstract

In the context of the European Union (EU) Horizon 2020 GRACIOUS project (Grouping, Read-Across, Characterisation and classification framework for regulatory risk assessment of manufactured nanomaterials and Safer design of nano-enabled products), we proposed a quantitative Weight of Evidence (WoE) approach for hazard classification of nanomaterials (NMs). This approach is based on the requirements of the European Regulation on Classification, Labelling and Packaging of Substances and Mixtures (the CLP regulation), which implements the United Nations' Globally Harmonized System of Classification and Labelling of Chemicals (UN GHS) in the European Union. The goal of this WoE methodology is to facilitate classification of NMs according to CLP criteria, following the decision trees defined in ECHA's CLP regulatory guidance. In the WoE, results from heterogeneous studies are weighted according to data quality and completeness criteria, integrated, and then evaluated by expert judgment to obtain a hazard classification, resulting in a coherent and justifiable methodology. Moreover, the probabilistic nature of the proposed approach enables highlighting the uncertainty in the analysis. The proposed methodology involves the following stages: (1) collection of data for different NMs related to the endpoint of interest: each study related to each NM is referred as a Line of Evidence (LoE); (2) computation of weighted scores for each LoE: each LoE is weighted by a score calculated based on data quality and completeness criteria defined in the GRACIOUS project; (3) comparison and integration of the weighed LoEs for each NM: A Monte Carlo resampling approach is adopted to quantitatively and probabilistically integrate the weighted evidence; and (4) assignment of each NM to a hazard class: according to the results, each NM is assigned to one of the classes defined by the CLP regulation. Furthermore, to facilitate the integration and the classification of the weighted LoEs, an online R tool was developed. Finally, the approach was tested against an endpoint relevant to CLP (Aquatic Toxicity) using data retrieved from the eNanoMapper database, results obtained were consistent to results in REACH registration dossiers and in recent literature.

Keywords: CLP regulation; Classification; Nanomaterials; Weight of evidence.