REACH: same substance identity RIP 3.10

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REACH same substance identity (RIP 3.10)
Dr. Erwin Annys Sr. Advisor Product Innovation
Policy WERCS 2007 EU User group Napoli 31/05/07
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What is the same substance two steps

• What is my substances ?
• Identification name, CAS number, EC number,
• Description
• Impurities
• Production process, purification process,
• Analytical data
• Spectra
• Chromatograms
• Is my substance the same as the substance of
  another registrant ?

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Substance identification is important

• REACH is based on substances
• There are changes from EINECS reporting rules
• For pre-registrations and registrations you need
  to define your substances
• Identification of same substances is important
  for data sharing/consortium/SIEF formation,
  grouping and for non-phase-in substance
  registrations
• Identification of the substance used to generate
  (existing) data is important

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REACH definition of substance

• A chemical element and its compounds in the
  natural state or obtained by any manufacturing
  process
• Including
• Any additive necessary to preserve its stability
• Any impurity deriving from the process used
• Excluding
• Any solvent which may be separated without
  affecting the stability of the substance or
  changing its composition

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REACH Definition of Substance

• The definition goes beyond the textbook
  definition of a pure compound defined by a
  single molecule
• RIP 3.10 explains how to interpret the definition
• RIP 3.10 explains how to name and describe
  substances for (pre-) registration

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Identification for pre-registration

• Full substance identification NOT required
• To be submitted
• Name of the substance (IUPAC or other
  international chemical name)
• EC-number (if available appropriate)
• CAS name and CAS number (if available)
• Substance identification to facilitate the
  formation of SIEFs

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Identification for registration

• Registration
• Shall include information on the identification
  of the substance
• Shall be adequate to enable each substance to be
  identified sufficiently
• If not technically possible or scientifically
  necessary to give information on a substance
  parameter a scientific justification is needed

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Identification for registration

• Identification parameters listed in Annex VI
• IUPAC and/or other names, EC-number, CAS name/
  number, other identifiers
• Molecular and structural information (e.g.
  formulae, MW, SMILES code, optical activity.)
• Chemical composition (constituents, impurities,
  additives for stabilization)
• Supporting analytical data (IR,UV, NMR, MS, HPLC,
  GC etc., as appropriate)

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Constituents

• Individual chemical species (molecules) in a
  substance are called constituents
• A substance consists of constituents
• A preparation consists of components or
  ingredients
• Constituent ? component or ingredient

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Types of substance

• Well defined substances
• Mono-constituent substances
• One main constituent 80
• Multi-constituent substances
• Two or more main constituents between 10 - 80
• In both cases ca.100 of the composition can be
  defined

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Types of substance

• Poorly defined or variable substances
• Also known as UVCB-substances of Unknown or
  Variable composition, Complex reaction products
  or Biological materials
• Cannot be sufficiently identified by their
  composition
• Number of constituents is relatively large
• Composition largely unknown, very variable or
  poorly predictable

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Mono-constituent substances

• One constituent substance
• Main constituent 80 (w/w)
• Impurities
• ? main constituent, impurities and additives
  100
• Impurities 1 and impurities relevant for
  classification must be mentioned (name, CAS nr,)
• Name name of the main constituent

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Mono-constituent substances
Examples
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Mono-constituent substances

• Deviation from 80 rule is possible with
  justification, if
• The range of concentrations for the main
  constituent and the impurities overlap the 80
  criterion and the main constituent is only
  occasionally 80
• The main constituent is can be shown to have similar physico-chemical
  properties and the same hazard profile as other
  mono-constituent substances with the same
  identity that fulfill the 80 rule

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Multi-constituent substances

• Multiple constituent substance
• Two or more constituents 10 en
• Impurities
• ? main constituents, impurities and additives
  100
• Impurities 1 and impurities relevant for
  classification must be mentioned (name, CAS nr,)
  
• Name mixture of

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Multi-constituent substances
Example
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Well defined but more identifiers needed

• Some substances need to be defined by more than
  just their chemical composition
• Same naming and identification rules as mono- or
  multi-constituent substances
• PLUS
• Other physical or characteristic parameters e.g.
  crystallomorphology, (geological) mineral
  composition
• Examples some crystalline inorganic minerals
  such as aragonite (a specific form of CaCO3)
• Additional analytical evidence required e.g.
  X-ray diffraction, elemental analysis

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UVCB substances

• Any substance which is not a well defined
  substance
• RIP 3.10 gives generic guidance on main
  parameters to identify UVCBs (additional to
  Annex VI part 2)
• If the substance can be fully identified it is
  wise to treat it as a well-defined substance, not
  a UVCB
• A UVCB of the same composition but derived from a
  different source and/or process is a different
  substance, and will likely require a separate
  registration
• Specific detailed guidance for
• Substances with variations in C-chain length
• Substances obtained from oil and oil-like sources

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General guidance for UVCBs

• Main constituents and impurities not really
  distinguished
• Chemical composition and identity of constituents
  should be given as far as is known
• Can describe in a more general way than for
  well-defined substances (e.g. linear fatty acids
  C8-C16)
• Composition can be described in terms of indexes,
  fingerprints, reference standards etc.
• All known constituents present at 10 should be
  specified by name, CAS number, typical
  concentration and ranges
• All constituents relevant for classification must
  be identified
• Unknown constituents identified by general
  chemical description, where possible

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General guidance for UVCBs

• Naming should be in the order of source and then
  process
• Biological sources are identified by the name of
  the species
• Non-biological sources are identified by the
  starting materials
• Processes are identified by
• Type of chemical reaction (e.g. alkylation,
  chlorination)
• Refinement step (e.g. extraction, fractionation,
  concentration)

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Types of UVCB substances

• Biological substances
• Process is synthesis
• Includes chemical or biochemical derivatives of
  plant extracts
• Process is refinement
• Includes extracts and concentrates of plant
  extracts
• Chemical and mineral substances
• Process is synthesis
• Poorly defined chemical reaction products
• Process is refinement
• Includes petroleum substances, purified minerals

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UVCB Example

• Chemical derivative of a plant extract
• Fatty acids, coco, compounds with diethanolamine
• UVCB because
• Complex mixture of amides formed from various
  fatty acids present in the coconut oil
• Ratio of fatty acids can vary in the source

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UVCB Example

• A refined product of a plant-derived substance
• Turpentine oil

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UVCB Example

• A chemical derivative of a chemical
• Reaction product of a di-carboxylic acid and
  amino-alcohol
• UVCB because
• Complicated mixture of amides and esters

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Checking if substances are the same

• Needs expert judgement
• Equivalent substances should contain the same
  main constituents
• Apply 80 (mono-const.) and 10 80
  (multi-const.) rules
• No differentation between pure, technical,
  analytical grades

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Checking if substances are the same

• If substances are similar enough then data
  sharing is possible
• However, if impurity profile differs markedly
  then data sharing (or even presence in same SIEF)
  may not be appropriate
• Data sharing may also be possible with similar
  (but not the same) substances by grouping,
  category approach, read-across (see RIPs 3.3 and
  3.4)

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Same/different substances examples

• Hydrates and water-free substances considered the
  same
• Chiral centres are mixture of racemates (in
  absence of proof of the contrary)
• Acids or bases and their salts are different
• Salts of different cations (Na, K, Ca, etc.) are
  different
• Branched vs linear, saturated vs unsaturated are
  different

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Remaining issues

• RIP 3.10 has not addressed all cases
• Reaction products issue
• Mixed reaction products must be registered as
  substance (multi-constituent or UVCB)
• Cannot register individual constituents
• UVCBs
• Different sources may mean different substances,
  even if composition is very similar
• RIP 3.10 appears to demand complete similarity
  to be the same substance

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Thanks for your attention