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Diss Factsheets

Administrative data

Description of key information

Skin sensitisation (QSAR target substance; GPMT, RIPT source substances): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation, other
Remarks:
QSAR
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
Principles of method if other than guideline:
- Principle of test: The OECD QSAR Toolbox v3.3 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry (http://toolbox.oasis-lmc.org). It contains several different databases with data on chemicals. The model was used to predict the skin sensitisation potential of the main constituents of the test substance in the database 'Protein binding alerts for skin sensitisation by OASIS v1.3'.
- Short description of test conditions: The SMILES code of the main constituents of the test substance is compared with funtional groups known to be related to potential skin sensitising properties.
- Parameters analysed / observed: A QSAR prediction of the skin sensitisation potential of the main constituents of the test substance was performed. The presence of protein binding alerts that may indicate a skin sensitising potential is assessed.
GLP compliance:
no
Key result
Run / experiment:
other: Skin sensitisation prediction as structural alerts
Parameter:
other: QSAR prediction
Vehicle controls validity:
not applicable
Negative controls validity:
not applicable
Positive controls validity:
not applicable
Remarks on result:
other: Negative for skin sensitising potential measured as structural alerts
Other effects / acceptance of results:
The predicted skin sensitisation potential of the main constituents of Dub TGI 24 as protein binding potential was modelled in the OECD QSAR Toolbox v3.3. The components fall within the model applicability domain for the database OASIS v1.3. No alerts were found. Therefore, the main constituents of Dub TGI 24 are not expected to have a skin sensitising potential and therefore the test substance Dub TGI 24 is not expected to have skin sensitising potential.
Interpretation of results:
study cannot be used for classification
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
11 May - 10 Sep 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
adopted in 1996
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Type of study:
Buehler test
Justification for non-LLNA method:
The study was performed prior to the relevant amendment of Regulation (EC) 1907/2006, stipulating that the Local lymph node assay (OECD 429) is the preferred in vivo study.
Species:
guinea pig
Strain:
other: Dunkin-Hartley, Pirbright White Hsd/Poc:DH
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany.
- Age at study initiation: young adults
- Weight at study initiation: < 500 g
- Housing: maximum 5 animals per cage in Type IV Makrolon cages.
- Diet: Ssniff G 4 diet in pellet form (laboratory standard guinea pig diet, Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70 (temporary deviations were caused by cleaning the animal room)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Induction: 50%
Challenge: 50%
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Induction: 50%
Challenge: 50%
No. of animals per dose:
10 (controls), 20 (in test groups)
Details on study design:
RANGE FINDING TESTS:
In a preliminary miscibility test, a test substance concentration of 50% (w/w) was determined as the highest concentration which was easily miscible and well applicable.
In a preliminary skin irritation test with 3 female animals, test substance formulations of 10, 20, 30 and 50% were topically applied to the flank under occlusive conditions for 6 h. The maximum non-irritant concentration of 50% was used for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in vehicle
- Control group: vehicle
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14
- Concentrations: 50% test substance in vaseline

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: test substance in vehicle and vehicle only
- Control group: test substance in vehicle and vehicle only
- Site: posterior right flank (test substance) and anterior right flank (vehicle)
- Concentrations: 50% test substance in vaseline
- Evaluation (hr after challenge): 24 and 48 h after test substance removal with corn oil.
Challenge controls:
In the 4th week of the test, 3 additional animals (accompanying group), kept under the same conditions, but without treatment, were used to re-determine the maximum non-irritant concentration for the challenge treatment.
This additional determination of the challenge concentration was carried out because it was suspected that the sensitivity of the skin changed as the weight of the animals increased. This ensured that the challenge concentration was determined on animals which had approximately the same weight as the 30 animals in the challenge phase. In this test, the concentrations administered and the experimental conditions corresponded to those of the preliminary test.
The determination of the challenge concentration in the 4th week of the test on 3 untreated animals of the same age led to no signs of dermal irritation in any animal 24 and 48 h post-application of formulations containing 10, 20, 30 and 50% test substance in vehicle.
On the basis of these results and the results of the induction period, the 50% test substance in vehicle was administered for the challenge treatment in the main test.
Since this test was conducted with untreated animals approximately at the same time as the challenge application, it can be considered as a challenge control test.
Positive control substance(s):
yes
Remarks:
α-hexylcinnamaldehyde
Positive control results:
The positive control substance α-hexylcinnamaldehyde (100% induction, 50% challenge concentration) induced positive reactions in 10/20 and 9/20 animals at 24 and 48 h after challenge, respectively. Thus, the reliability criteria for the Buehler test (≥ 15% positive response) were met.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Interpretation of results:
other: CLP/GHS EU criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
11 May - 10 Sep 1998
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted in 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
adopted in 1996
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Ministerium für Umwelt, Raumordnung und Landwirtschaft des Landes Nordrhein-Westfalen, Düsseldorf, Germany
Type of study:
Buehler test
Species:
guinea pig
Strain:
other: Dunkin-Hartley, Pirbright White Hsd/Poc:DH
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany.
- Age at study initiation: young adults
- Weight at study initiation: < 500 g
- Housing: maximum 5 animals per cage in Type IV Makrolon cages.
- Diet: Ssniff G 4 diet in pellet form (laboratory standard guinea pig dietdiet, Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70 (temporary deviations were caused by cleaning the animal room)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Induction: 50%
Challenge: 50%
Route:
epicutaneous, occlusive
Vehicle:
petrolatum
Concentration / amount:
Induction: 50%
Challenge: 50%
No. of animals per dose:
10 (controls), 20 (in test groups)
Details on study design:
RANGE FINDING TESTS:
In a preliminary miscibility test, a test substance concentration of 50% (w/w) was determined as the highest concentration which was easily miscible and well applicable.
In a preliminary skin irritation test with 3 female animals, test substance formulations of 10, 20, 30 and 50% were topically applied to the flank under occlusive conditions for 6 h. The maximum non-irritant concentration of 50% was used for challenge.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 h
- Test groups: test substance in vehicle
- Control group: vehicle
- Site: left flank
- Frequency of applications: every 7 days
- Duration: Days 0-14
- Concentrations: 50% test substance in vaseline

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 28
- Exposure period: 6 h
- Test groups: test substance in vehicle and vehicle only
- Control group: test substance in vehicle and vehicle only
- Site: posterior right flank (test substance) and anterior right flank (vehicle)
- Concentrations: 50% test substance in vaseline
- Evaluation (hr after challenge): 24 and 48 h after test substance removal with corn oil.
Challenge controls:
In the 4th week of the test, 3 additional animals (accompanying group), kept under the same conditions, but without treatment, were used to re-determine the maximum non-irritant concentration for the challenge treatment.
This additional determination of the challenge concentration was carried out because it was suspected that the sensitivity of the skin changed as the weight of the animals increased. This ensured that the challenge concentration was determined on animals which had approximately the same weight as the 30 animals in the challenge phase. In this test, the concentrations administered and the experimental conditions corresponded to those of the preliminary test.
The determination of the challenge concentration in the 4th week of the test on 3 untreated animals of the same age led to no signs of dermal irritation in any animal 24 and 48 h post-application of formulations containing 10, 20, 30 and 50% test substance in vehicle.
On the basis of these results and the results of the induction period, the 50% test substance in vehicle was administered for the challenge treatment in the main test.
Since this test was conducted with untreated animals approximately at the same time as the challenge application, it can be considered as a challenge control test.
Positive control substance(s):
yes
Remarks:
α-hexylcinnamaldehyde
Positive control results:
The positive control substance α-hexylcinnamaldehyde (100% induction, 50% challenge concentration) induced positive reactions in 10/20 and 9/20 animals at 24 and 48 h after challenge, respectively. Thus, the reliability criteria for the Buehler test (≥ 15% positive response) were met.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 50% . No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Interpretation of results:
other: CLP/GHS EU criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
CLP: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across

There are no experimental data on the skin sensitisation potential of Dub TGI 24 available. The assessment was therefore based on QSAR modelling, and animal and human 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 

CAS 91052-08-3

The potential for the mono-, di- and triglyceride of Dub TGI 24 to exhibit skin sensitising properties was predicted in the QSAR OECD toolbox (please refer to IUCLID section 7.4.1). The results for these components are considered to be representative for the target substance. Based on the results predicted with the OECD toolbox, there was no alert for skin sensitisation potential in the database OASIS v1.3, as estimated based on protein binding potential.

Animal data

CAS 555-43-1

Glycerol tristearate was tested for its skin sensitisation potential in a Guinea pig maximization test according to OECD guideline 406 (Buehler test) and under GLP conditions (please refer to IUCLID section 7.4.1). On Day 0 of the induction phase of the main study, a 50% dilution of the test substance in vaseline was applied to the clipped skin area on the left flank of 20 Dunkin-Hartley guinea pigs for 6 hours. The epicutaneous induction treatment was repeated on Day 7 and 14. A control group consisting of 10 animals was treated with vehicle only. On Day 28, the challenge treatment was performed by topical application of the test substance at 50% concentration in vaseline and the vehicle to the right flank of all animals for 6 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 caused by the challenge treatment with the test substance at 50% in any of the animals of the treatment and control groups. The positive control was shown to be valid. The test substance had no sensitising effect in guinea pigs under the experimental conditions.

Human data

CAS 77538-19-3

A Human Repeat Insult Patch Test (RIPT) with 93 volunteers was performed to investigate the skin sensitisation potential of docosanoic acid ester with 1,2,3-propanetriol (please refer to IUCLID section 7.4.1). For the induction period, a series of nine induction patchings was performed over a period of 3 weeks. In each induction treatment, the undiluted test substance was occlusively applied to the skin of the volunteers for 24 h. The patches were then removed and the skin was scored. After a rest period of 2 weeks, the challenge was performed by application of the test substance for a period of 24 h. The application sites were scored at about 24, 48, 72 and 96 hours after patch removal. None of the 93 volunteers showed positive skin reactions at any of the reading time points. Therefore, under the conditions of this RIPT, the test substance was not considered to have any sensitising potential.

Overall conclusion for skin sensitisation

A weight-of-evidence approach was applied to assess the skin sensitising potential of the target substance Dub TGI 24. The OECD QSAR Toolbox did not predict protein binding indicative for sensitising properties of the mono-, di- and triester of the target substance. A GPMT study and a RIPT study performed with two source substances were negative. Taking into account the available information, Dub TGI 24 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 Dub TGI 24, data will be generated from data available for reference source substance(s) 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 data on the target substance and the analogue read across approach, 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.