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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (read-across modified LLNA and GPMT; QSAR prediction on target): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation, other
Remarks:
QSAR skin sensitisation profiling and prediction
Type of information:
(Q)SAR
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification
Justification for type of information:
1. SOFTWARE
OECD QSAR Toolbox: a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry, Burgas, Bulgaria (http://toolbox.oasis-lmc.org).

2. MODEL (incl. version number)
OECD QSAR Toolbox v4.2

3. SMILES OR OTHER IDENTIFIERS USED AS INPUT FOR THE MODEL
See “Test material information”

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
See "Any other information of materials and methods incl. tables"

5. APPLICABILITY DOMAIN
See "Any other information of materials and methods incl. tables"

6. ADEQUACY OF THE RESULT
The results may be used in a weight-of-evidence approach together with other information to reach a conclusion regarding the skin sensitising potential of the test substance.
Qualifier:
according to guideline
Guideline:
other: REACH Guidance on QSARs
Deviations:
not applicable
GLP compliance:
no
Key result
Parameter:
other: QSAR prediction
Remarks on result:
other: no indication for skin sensitisation
Interpretation of results:
other: The prediction results were negative for skin sensitising potential, based on QSAR prediction (OECD QSAR Toolbox v4.2, ECHA database).
Conclusions:
The skin sensitisation potential of Esterification product of glycerol and C8-C12 (even numbered) fatty acids was predicted using OECD QSAR Toolbox v4.2. The prediction for skin sensitisation (II, ECETOC) was negative for both SMILES codes representing the two main constituents of the UVCB substance. The test substance falls within the domain for profiling based on Protein binding alerts for skin sensitisation by OASIS (primary grouping).
Endpoint:
skin sensitisation, other
Remarks:
in vivo (LLNA and non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
weight of evidence
Justification for type of information:
refer to analogue justification provided in IUCLID section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Source: CAS 91845-19-1
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction: 1%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Source: CAS 91845-19-1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Source: CAS 91845-19-1
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 1%; challenge: 25%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Source: CAS 91845-19-1
Key result
Parameter:
SI
Value:
0.84
Test group / Remarks:
2%
Remarks on result:
other: Source: CAS 97593-30-1
Key result
Parameter:
SI
Value:
0.95
Test group / Remarks:
10%
Remarks on result:
other: Source: CAS 97593-30-1
Key result
Parameter:
SI
Value:
0.97
Test group / Remarks:
50%
Remarks on result:
other: Source: CAS 97593-30-1
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.
Conclusions:
The read-across application is justified in the analogue justification. Based on the available data, the target and source substances are considered not to show differences in skin sensitising properties.The available data on suitable source substances did not show any skin sensitising effects. Therefore, the target substance is not predicted to be a skin sensitiser.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Read-across justification

No data on the skin sensitisation potential of Esterification product of glycerol and C8-C12 (even numbered) fatty acids (old CAS 26402-22-2) are available. The assessment was therefore based on QSAR modelling and studies conducted with analogue (source) substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

 

Skin sensitisation

 

QSAR predictions 

Old CAS 26402-22-2

The potential for Esterification product of glycerol and C8-C12 (even numbered) fatty acids to be a skin sensitiser was predicted in the QSAR OECD Toolbox v4.2 (WoE, 2018). No general mechanistic protein binding alert was found. No endpoint specific protein binding alerts for skin sensitisation according to GHS or by OASIS were found.

 

CAS 97593-30-1

The skin sensitising potential of Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was investigated in a modified Local Lymph Node Assay (LLNA) in mice performed according to OECD guideline 429 and in compliance with GLP (WoE, 2008). In this study, 6 female Hsd Win:NMRI mice per test group were treated with test substance at concentrations of 2, 10 and 50% in acetone/olive oil (4:1 v/v) or with the vehicle alone. The test substance formulations or the vehicle were applied epicutaneously onto the dorsal part of each ear (25 µL/ear) for three consecutive days. In order to assess skin irritation, the thickness of both auricles of the animals was measured before the first treatment and prior to sacrifice. In addition, ear weights were determined at necropsy. On Day 4, animals were sacrificed and weight of the lymph nodes was determined. The cell proliferation of pooled lymph nodes from individual animals was measured by counting the cells in suspension using an electronic cell counter. The mean cell count (1000 cells/mL lymph node suspension) for each test group was 9169, 10421 and 10630 at concentrations of 2, 10 and 50% of the test substance, respectively. Treatment with the test substance did not result in a significant increase of absolute number of lymph node cell counts per mL compared with the control group. Based on these results, cell count indices of 0.84, 0.95 and 0.97 were calculated for treatment concentrations of 2, 10 and 50%, respectively. A positive result in this strain of mice was obtained if the cell count index was ≥ 1.4. No local or systemic toxicity and no effects on body weights were observed. No effects on ear weights and ear swelling were observed in the treated animals compared to controls. The historical positive control alpha hexyl cinnamic aldehyde at concentrations of 3, 10 and 30% confirmed the validity of the method. Under the conditions of this study, the test substance was not found to be a sensitiser in the modified LLNA.

CAS 91845-19-1

The skin sensitising potential of Glycerides, C16-18 and C18-hydroxy mono- and di- was studied in guinea pigs according to the maximisation method (OECD guideline 406) and in compliance with GLP (WoE, 1985). In three preliminary tests, suitable treatment concentrations for the main study were determined in each 5 animals. For the intradermal route, the test substance at concentrations of 1 and 10 % in paraffin was administered to the clipped skin of 5 animals. Based on the induction of moderate irritant effects on the skin but no necrosis, a test substance concentration of 1% in paraffin oil (w/w) was chosen for intradermal injections in the main study. For the cutaneous route, the test substance at 25 and 50% in vaseline was applied to the clipped skin of 5 animals for 48 h using an occlusive dressing within the preliminary experiment. Since the 50% concentration of the test substance was sufficient to cause skin irritation, this concentration was selected for topical application in the induction phase of the main experiment. For challenge exposure, intradermal injections with Freund’s adjuvant followed by epicutaneous application of 0.2 g of the test substance at concentrations of 25 and 50% in vaseline were performed in the preliminary test. After 24-h exposure under occlusive conditions, slight erythema was observed on the skin of 2/5 animals. Thus, the test substance at 25% in Vaseline was chosen for topical application in the challenge phase of the main test. In the induction phase of the main study, intradermal injections of the test substance at 1% in paraffin and/or FCA were applied into the clipped skin area of 20 females. A control group, consisting of 20 females, was injected with vehicle only and/or FCA. On Day 8, a 48-hour epicutaneous induction treatment with test substance at 50% in vaseline or vehicle only was performed in the treated or control animals on the regions of intradermal injections. On Day 22, the challenge treatment was performed by topical application of the test substance at 25% concentration in vaseline and the vehicle to all animals for 24 h. Skin reactions were evaluated 24 and 48 h after the challenge application. During the study no test substance-related clinical signs and no effects on body weight gain were observed. No cutaneous reactions were provoked by the challenge treatment with the test substance at 25% in none of the animals of the test and control groups. Therefore, the test substance had no sensitising effect in guinea pigs under the experimental conditions chosen.

Overall conclusion for skin sensitisation

A weight-of-evidence approach was applied to assess the skin sensitising potential of the target substance Esterification product of glycerol and C8-C12 (even numbered) fatty acids. The OECD QSAR Toolbox did not predict skin sensitising properties for the target substance. The studies (LLNA, GPMT) performed with two source substances were negative. Taking into account the available information, Esterification product of glycerol and C8-C12 (even numbered) fatty acids is not expected to be skin sensitising.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Esterification product of glycerol and C8-C12 (even numbered) fatty acids, data will be generated from reference source substance(s) and QSAR predictions to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

Therefore, based on the analogue read-across approach combined with QSAR analyses performed with the main components, the available data on skin sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.