Client
REACH Consortium of metal industry companies.
Background
Manufacturers of chemicals in, or importers into, the European Union are required under the REACH regulation to submit a dossier of information on their substances to ECHA. The substantial data package required includes relevant toxicological data, with minimum data endpoint requirements dependent on e.g. tonnage and potential exposure.
Project goals
To support a large consortium with all the mammalian toxicology aspects of their REACH registration obligations for a group of more than 80 related metal compounds.
Approach and outcome
Working alongside trusted partners to provide technical support to the consortium, bibra had responsibility for ensuring that the mammalian toxicology aspects of the submission were addressed in an expert, timely and cost-efficient manner.
We were involved in all aspects of the consortium’s REACH registration programme, including exemption advice (e.g. Annex VIII derogations), identification of relevant existing information following comprehensive literature searches (including in our in-house database TRACE), extensive data-gap analyses (DGAs), preparation of endpoint study records (ESRs) and associated endpoint summaries (ESs) in IUCLID, and advising on appropriate Integrated Testing Strategies (ITS) using data waiving, read-across and weight-of-evidence (WoE) approaches where considered scientifically justifiable. A primary aim was to minimise the need for additional testing, particularly any studies involving vertebrate animals. Bibra was also closely involved with commissioning and monitoring of the testing programme, advising on the impact of generated results on the testing strategy going forwards and assessing the implications for the overall regulatory submission.
We also prepared toxicokinetic (TK) assessments for all Annex VIII-X substances, based on existing ADME studies and TK predictions from the structure, molecular weight, physical-chemical parameters (for example vapour pressure and solubility) and respiratory tract modelling (e.g. mass median aerodynamic diameter (MMAD) values). These enabled expert predictions, notably of absorption levels by different exposure routes, and informed the calculation of derived no effect levels (DNELs) or derived minimal effect levels (DMELs) for these metal compounds. Where the data were not sufficient to derive a DNEL or DMEL, then a qualitative assessment was conducted (for example for some of the respiratory sensitisers). Bibra also assisted with the human health classification and labelling of these metal compounds according to EU CLP criteria (1272/2008), the PBT/vPvB assessments, the production and editing of the Chemical Safety Reports (CSRs), and proposed suitable and appropriate Risk Management Measures (RMMs) and Operational Conditions (OCs).
