Substance Characterisation for REACH. Dr Emma Miller Senior Chemist

Transcription

1 Substance Characterisation for REACH Dr Emma Miller Senior Chemist

2 Submission of a REACH registration dossier, either as a lead registrant or a joint registrant Submission of an Inquiry to ECHA Submission of a PPORD Notification Application for Authorisation Substance Characterisation and REACH When is characterisation required under REACH? PPORD = Product and Process Orientated Research and Development

3 Substance Identity and REACH Substance identity One substance, one registration A registration under REACH is based on the identity of the registered substance Characterisation is a fundamental part of demonstrating substance identity Substance identification therefore constitutes an essential element for the purpose of REACH and needs to be unambiguous and comprehensive

4 Substance Identity and Sameness The importance of substance characterisation Every registrant must demonstrate sameness to justify data sharing In practice, sameness means the substance identity agrees with the Substance Identification Profile (SIP) agreed within the SIEF Data sharing may still be possible in cases where a substance does not fit in with the SIP but classification may differ Important for classification The main substance itself but also any impurities present that could affect the overall classification Ensures Risk Management Measures are appropriate

5 Sameness and Data Sharing The consequences of poor characterisation Difficult to justify sharing endpoint data without proof of sameness Justification of read-across strategies may be weakened Inconclusive identity data found by ECHA during the examination of testing proposals may lead to the initiation of a targeted compliance check

6 The consequences of poor characterisation Dossier Checks ECHA has stated that it will evaluate 5% of all dossiers submitted Evaluation of 5% of all dossiers for the highest tonnage bands was completed by the end of % of dossiers checked failed to comply with one or more of the information requirements of REACH. One of the main areas of concern was substance identity Evaluation Under REACH: Progress Report 2013 (ECHA)

7 Selected issues identified 1 Composition reported with no constituents ECHA Identity IT Screening Campaign Low or ambiguous degree of purity for well-defined substances Unidentified constituent or impurity present at significant concentration Well-defined substance with inconsistency between degree of purity and constituent or impurity concentrations No spectral and analytical information provided Additives without stabilising function 1. Excerpt from webinar by L Majoros, Substance identity screening of the registration dossiers, ECHA, 30/04/2014

8 Substance Characterisation The process Generation and presentation of analytical data to demonstrate the identity and composition of the substance It involves: Design of a robust, technically appropriate analytical test strategy Laboratory testing Interpretation of data and compilation of the test report Inclusion of the appropriate information into IUCLID

9 IUCLID Dossier Section 1.2 Composition Joint Registrants and Lead Registrants Typical concentrations and concentration ranges Lead Registrants only

10 IUCLID Dossier Section 1.4 Analytical Information

11 The Substance Identification Profile (SIP) Information from the SIEF It is important to obtain the SIP Sameness criteria - constituents, concentration ranges, impurities Analytical advice may also be offered Each registrant must check whether any recommended analytical strategies are appropriate in their particular case Ultimately, it is ECHA that will check substance identity and sameness not the lead registrant or consortium

12 Analytical Methods REACH Regulation, Annex VI, Item Optical activity and isomer ratio Molecular weight (range) Degree of purity (%) Nature of impurities Percentage of main impurities Nature and order of magnitude of any additives Spectral data High performance liquid chromatography or gas chromatography

13 Analytical Strategy Design In practice. Use good technical judgement rather than a literal translation of Annex VI Characterisation should be sufficient and appropriate Technically relevant, independent techniques that are mutually supportive In-house assays do not necessarily provide characterisation data Check for consistency of results Overall composition and mass balance are important Would the analytical data demonstrate identity and composition to an independent scientist? If certain tests are not performed, a technical explanation should be provided (for the principal techniques listed in Annex VI)

14 Analytical Strategy Design Assessment of the substance Organic or inorganic Complexity Physical form Solubility Stability Isolated or formed in situ

15 Scope of Testing Example: Manufacture of substance C A + B C + D + E.. Understanding the chemistry and the process is important Although focus is on characterising C, must also consider: - Possible by-products (D and E) - Residual starting materials (A and B) and their associated impurities - Any residual catalysts or other agents used to mediate the reaction - Impurities should be specified as described earlier - Additives deliberately introduced to preserve stability

16 Important Analytical Techniques Chemical Identity Spectroscopy Nuclear magnetic resonance spectroscopy 1 H and 13 C NMR are commonly used for organic substances Other nuclei, e.g. 29 Si, may be appropriate, especially for inorganic substances Solution and solid state NMR available Infrared spectroscopy Gives information about the type of bonds present, ionisation and substitution Complete spectral fingerprints are useful for comparison with standards Electronic spectroscopy UV-visible is the most common, especially for organic substances Atomic absorption/emission is useful for metals Mass spectrometry Molecular/atomic mass of the substance Characteristic isotope ratios Characteristic fragmentation patterns for comparison with reference libraries

17 Important Analytical Techniques Chemical Composition - Chromatography Gas chromatography Useful for substances that are thermally stable and volatile below 400 C Provides composition and purity profile Quantitative and semi-quantitative Can be used in tandem with other techniques, particularly mass spectrometry, but detector response factors between different components must be considered High performance liquid chromatography Good for non-volatile, soluble substances Quantitative and semi-quantitative Can be used in tandem with other techniques, particularly mass spectrometry, for component identification (response factors important, as above) Ion chromatography Especially important for ionic inorganic substances

18 Identity, Composition, Physical Attributes Important Analytical Techniques Inductively coupled plasma and X-ray fluorescence Identification and quantification of various elements, particularly metals X-Ray diffraction Identification of solid substances, typically crystalline powders, by comparison with reference libraries Quantitative information is possible by data refinement (Rietveld) Titration Acids, bases, metal speciation, water content etc Special consideration for nanomaterials or substances where physical morphology is a key sameness criterion Scanning electron microscopy Specific surface area Particle size analysis

19 Mono- and multi-constituent substances Well-defined Substances Important to include: Spectroscopy for structure and identity information Chromatography to provide purity profile and to identify and quantify impurities Any other relevant tests to support the characterisation process Generally possible to interpret and assign spectroscopic signals and chromatographic features Analysis should allow specification of impurities present >1% and any of relevance for classification or PBT assessment (regardless of their concentration)

20 EXAMPLES Mono- and multi-constituent substances Well-defined Substances 1 H NMR FT-IR GC-FID

21 Complex Substances UVCB substances Spectroscopy/ chromatography Often difficult to assign all individual peaks and features Should allow specification of major known components, especially those present >10% and any of relevance for classification or PBT assessment (regardless of their concentration) Fingerprints Complex yet characteristic spectral or chromatographic profiles Comparison with reference material important (laboratory samples/databases/literature) Other identifiers are important These can include physico-chemical parameters such as morphology and boiling range

22 EXAMPLES UVCBs Complex Substances Fingerprints 1 H NMR GC-MS Other identifiers

23 Supporting Information Analytical documentation Must provide a Description of the analytical methods...sufficient to allow the methods to be reproduced (REACH Annex VI) The following information should be provided with each analytical study: Substance name, structural formula, source, batch #, date etc Equipment used: Make, model, configuration Experimental details: Sample preparation, instrument methods, calibration information and raw data, calculations etc Good quality spectra and chromatograms with signal assignments and conclusions The name of the analytical laboratory and analyst responsible Bibliographic references where applicable

24 In Conclusion Good Practice Make use of all the available information when planning analytical work Be thorough and show due diligence (manufacturing process) Ensure the sample tested is representative of what is manufactured or imported Provide good quality spectra, chromatograms, calibration data/graphs, raw data and calculations Interpret and document the work thoroughly Provide technical justification for specific tests not undertaken Provide conclusions and ensure the results account for 100% of the substance (including additives) Be objective: Does the analytical evidence provide unequivocal evidence of identity and composition?

25 Available white papers on substance characterisation entific_analytical_services.php

26 Thank you Dr Emma Miller Senior Chemist twitter.com/thereachcentre