reach: same substance identity (rip 3.10) dr. erwin annys sr. advisor product & innovation...
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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 < 10% (w/w) ∑ 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
Main Constituent
% Impurity % Name
m-xylene 91 o-xylene 5 m-xylene
o-xylene 87 m-xylene 10 o-xylene
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 < 80% but the substance 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 <
80% Impurities < 10% ∑ 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
Main Constituents
% Impurity % Name
m-xylene
o-xylene
50
45
p-xylene 5 Mixture of: m-xylene and o-xylene
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 UVCB’s (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 UVCB’s
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
EC 263-153-4 CAS 61790-63-4
Condensation products of coco fatty acids and diethanolamine
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UVCB Example A refined product of a plant-derived
substance: Turpentine oil
EC: 232-350-7
CAS: 8006-64-2
Any of the volatile predominately terpenic fractions or distillates resulting from the solvent extraction of; gum collection from, or pulping of softwoods. Composed primarily of the C10H16 terpene hydrocarbons: alpha-pinene, beta-pinene, limonene, 3-carene, camphene. May contain other acyclic, monocyclic or bicyclic terpenenes, oxygenated terpenes and anethole. Exact composition varies with refining methods and the age, location and species of the softwood source
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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
EC 294-006-2 CAS: 91672-02-5
Reaction products of nonanedioicacid and 2-amino-2-methyl-1-propanol
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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 UVCB’s:
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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