REACH: same substance identity (RIP 3.10) Dr. Erwin Annys Sr. Advisor Product & Innovation Policy...

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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WERCS EU User group 2007 – Erwin Annys

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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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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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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REACH: same substance identity (RIP 3.10) Dr. Erwin Annys Sr. Advisor Product & Innovation Policy...

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