Registration Dossier

Administrative data

Description of key information

Skin sensitisation in vitro: studies technically not feasible

Skin sensitisation in vivo: new in vivo tests on Ginger oil CO2-Total Extract is waived based on Article 18 of the Cosmetics Regulation (CR, EC No 1223/2009)

Skin sensitisation based on constituent calculation: sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation, other
Remarks:
Classification based on calculation rules for mixtures of the CLP Regulation
Type of information:
calculation (if not (Q)SAR)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
accepted calculation method
Qualifier:
no guideline required
Principles of method if other than guideline:
Classification based on calculation rules for mixtures of the CLP Regulation
Key result
Parameter:
other: classification
Remarks on result:
other: Skin sensitizer category 1B
Interpretation of results:
other: Skin sensitiser Category 1
Remarks:
in accordance with EU CLP (EC 1272/2008 and its updates)
Conclusions:
Ginger CO2-Total Extract contains constituents that are classified as skin sensitisers Cat.1 and are all potentially present above the CLP generic concentration limit of 1% that triggers classification of the mixture. Therefore, the registered substance is classified as a skin sensitiser Cat. 1
Executive summary:

The decision logic for classification of mixtures from the ECHA Guidance on the Application of the CLP Criteria (2017) was used to determine the skin sensitising potential of

Ginger oil CO2-Total Extract. The substance not been tested itself in vitro/in chemico or in vivo, but some individual constituents are suspected or have been classified as skin sensitizers (see table) and are all present or potentially present above the generic concentration limit of 1 %. Therefore Ginger oil CO2-Total Extract shall be classified as a skin sensitizer without further testing according to the Regulation (EC) No 127212008.

Source: ECHA disseminated dossiers

NAME

CAS

Ginger CO2 -Total Extract

C&L inventory

alpha zingiberene

495-60-3

5.00%

21.00%

Has been notified as H317 in the C&L inventory, and indicated as a suspected skin sensitiser in the Annex III inventory: CAESAR skin sensitisation model in VEGA (Q)SAR platform predicts that the chemical is Sensitizer (good reliability)

Citral

5392·40-5

0.50%

3.00%

Has been notified as H317 in the C&L inventory, and subject to harmonised classification H317 as Skin Sens. 1A, H317

6-gingerol

23513-14-6

11%

22%

Suspected skin sensitiser: CAESAR skin sensitisation model in VEGA (Q)SAR platform predicts that the chemical is Sensitizer (moderate

reliability)

Endpoint:
skin sensitisation: in vitro
Data waiving:
study technically not feasible
Justification for data waiving:
other:
Justification for type of information:
See also full justification report under "Attached justification".
Scientific Justification to perform an in vivo Skin sensitization study to fulfil the REACH Regulation (EC) 1907/2006: Annex VII - 8.3 information Requirement
The attached document concerns the approach to the end point for skin sensitisation of the Natural Complex Substances (NCS) obtained from three grades of Ginger extracts (Zingiber officinale total extract (TE), selective extract (SE), hot flavour (HF)). These extracts are all made from the roots of the Zingiber Officinale (Zingiberaceae) plants and produced using a supercritical CO2 extraction process. Therefore Ginger extracts are of UVCB sub-type 3 where the source is biological and the process is a refinement;

It explains the reasons for an in-vivo LLNA study as the method of choice instead of the in-vitro test methods as the preferred approach to determine the potential skin sensitisation properties of a substance, when registered under the REACH Regulation (EC 1907/2006, Annex VII -8.3). This choice is based on:
- A thorough review of available data for the purpose of hazard classification, labelling and risk assessment.
- A consideration to apply QSAR or read-across for that purpose
- The partly unknown and variable composition of the NCSs.
- The variable solubility in water and other solvents of the known constituents of the NCS.
- The variable octanol/water partition coefficient of the known constituents, which are for a large part above 4 (TE 43%, SE 75%, HF 25% w/w of the substance).
- The uncertainty about the presence of (un)known constituents which can possibly act as pre- or post-haptens

The reasoning is supported with
- A list of dominant constituents and concentration ranges
- The ranges of the unknown part of the NCS
- The relevant physical chemical parameters.
Endpoint:
skin sensitisation: in vivo (LLNA)
Data waiving:
study waived due to provisions of other regulation
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
Attached to this record is provided a statement in which the registrant declares the sole cosmetic use of this substance.
Article 18 of the Cosmetics Regulation (CR, EC No 1223/2009) establishes a prohibition to test finished cosmetic products and cosmetic ingredients on animals (testing ban), and a prohibition to market in the EU finished cosmetic products and ingredients included in cosmetic products which were tested on animals for cosmetics purposes (marketing ban). A testing ban on finished cosmetic products applies since 11 September 2004; a testing ban on cosmetic ingredients or combination of ingredients applies since 11 March 2009. A marketing ban for products containing ingredients tested outside the EU applies since 11 March 2013, irrespective of the availability of alternative non-animal tests. In general terms, the provisions of the REACH apply to substances and preparations used in cosmetic products. However, REACH shall apply without prejudice to the CR as regards testing involving vertebrate animals within the scope of the CR (Article 2/4/b). Moreover, the above statement is confirmed by ECHA in the “Interface between REACH and Cosmetics regulations 2014a” factsheet (ECHA-14-FS-04-EN). Knowing that the test substance (Ginger -selective extract) is only and exclusively used in the formulation for cosmetic purposes, no animal testing is possible to assess the skin sensitisation in vivo endpoint, and therefore this in vivo study is not conducted.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

Existing data

All existing data were reviewed and documented by the applicant. There is no reliable (Klimisch score 1 to 2) existing data on the substance to be registered.

The existing data under review possessed inadequate or inconsistent information on the test item definition in line with the substance to be notified/registered. No studies were considered reliable or relevant for assessment (Klimisch score 3) on the basis of inadequate test item information. The data were therefore inapplicable with the requirements for the endpoint including within a REACH Annex XI: Section 1.2 weight of evidence adaptation. Specifically, it would not be possible to draw a conclusion in accordance with Regulation (EC) 1907/2006: Section 8.3 on information allowing a conclusion as to whether the substance would be considered to be or presumed to be a Skin Sensitizer Category 1A or not. The existing data offer no basis for a conclusion on this end point.

Constituent Data

The decision logic for classification of mixtures from the ECHA Guidance on the Application of the CLP Criteria (2017) was used to determine the skin sensitising potential of

Ginger oil CO2-Total Extract. The substance not been tested itself in vitro/in chemico or in vivo, but some individual constituents are suspected or have been classified as skin sensitizers (see table) and are all present or potentially present above the generic concentration limit of 1 %. Therefore Ginger oil CO2-Total Extract shall be classified as a skin sensitizer without further testing according to the Regulation (EC) No 127212008.

Source: ECHA disseminated dossiers

NAME

CAS

Ginger CO2-Total Extract

C&L inventory

alpha zingiberene

495-60-3

5.00%

21.00%

Has been notified as H317 in the C&L inventory, and indicated as a suspected skin sensitiser in the Annex III inventory: CAESAR skin sensitisation model in VEGA (Q)SAR platform predicts that the chemical is Sensitizer (good reliability)

Citral

5392·40-5

0.50%

3.00%

Has been notified as H317 in the C&L inventory, and subject to harmonised classification H317 as Skin Sens. 1A, H317

6-gingerol

23513-14-6

11%

22%

Suspected skin sensitiser: CAESAR skin sensitisation model in VEGA (Q)SAR platform predicts that the chemical is Sensitizer (moderate

reliability)

Justification for classification or non-classification

Based on the potential for skin sensitisation of the individual constituents alpha zingiberene, citral, and 6-gingerol which make up approximately 37% (typical value) of the UVCB, Ginger CO2-Total Extract needs to be classified as Skin Sens. 1, H317 in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC).