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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

QSAR: not sensitising

In vivo (Buehler test, read across): not sensitising

In vivo (LLNA, read across): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation, other
Remarks:
: QSAR prediction on skin sensitisation
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
The OECD QSAR Toolbox v4.1 is 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 version 4.1

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 are 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
Principles of method if other than guideline:
- Principle of test: The OECD QSAR Toolbox v4.1 is a Quantitative Structure-Activity Relationship model that was developed by the Laboratory of Mathematical Chemistry, Burgas, Bulgaria. (http://toolbox.oasis-lmc.org).
GLP compliance:
no
Key result
Parameter:
other: QSAR
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
other: The prediction results was negative for skin sensitising potential, based on QSAR prediction (OECD QSAR Toolbox v4.1).
Conclusions:
The skin sensitisation potential of Glycerol trioctanoate was predicted negative by OECD QSAR Toolbox v4.1. Therefore Glycerol trioctanoate is not expected to have a skin sensitising potential.
Endpoint:
skin sensitisation: in vivo (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:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other:
Remarks:
Source: CAS 620-67-7
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other:
Remarks:
Source: CAS 620-67-7
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other:
Remarks:
Source: CAS 620-67-7
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other:
Remarks:
Source: CAS 620-67-7
Reading:
other: reading at regular intervals
Group:
positive control
Remarks on result:
other: The sensitivity of the guinea pig strain used to reaction and effect of the known sensitiser 1-chlor o-2,4-dinitrobenzene was stated to be checked at regular intervals
Remarks:
No further details provided.

The in vivo skin sensitisation data from the source substance propane-1,2,3-triyl trisheptanoate (CAS 620-67 -6) was obtained from a study conducted according to OECD guideline 406 (Buehler test) under GLP conditions, and was selected as most suitable within the available source substance data based on study reliability and chemical structure similarity to the target substance. In vivo skin sensitisation data (LLNA) of an additional substance with similar structure was available and used as source substance in a weight of evidence approach.

Results from additional source substance (in vivo LLNA assay):

Parameter

Value

Variability

Test group

Remarks

Cell count index

1

± 27.43% (standard deviation)

vehicle control

 

Cell count index

0.84

± 32.82% (standard deviation)

2%

 

Cell count index

0.95

± 20.12% (standard deviation)

10%

 

Cell count index

0.97

± 20.22 (standard deviation)

50%

 

Cell count index

1.4

not reported

positive control

non-concurrent positive level exclusively defined for the NMRI outbred mice used in this study

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their skin sensitisation potential. In a Buehler test performed in guinea pigs with the source substance propane-1,2,3-triyl triheptanoate (CAS 620-67-7) no indication for skin sensitisation was found. In a local lymph node assay (LLNA) performed in mice with the source substance glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates (CAS 97593-30-1), no skin sensitisation was observed. Therefore, no skin sensitisation potential is expected for target substance glycerol trioctanoate (538-23-8).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Justification for read-across

No data on the skin sensitisation of glycerol trioctanoate (CAS 538-23-8) 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 prediction

CAS 538-23-8

The skin sensitizing potential for glycerol trioctanoate (CAS 538-23-8) was assessed using the QSAR OECD Toolbox v4.1 (WoE, 2017). The test substance falls within the model applicability domain for the database ‘ECHA CHEM’. The result of the prediction was negative, meaning that no skin sensitising potential was predicted.

 

In vivo

CAS 620-67-7

The skin sensitisation potential of propane-1,2,3-triyl trisheptanoate was studied in female guinea pigs according to the non-adjuvant Buehler method (OECD guideline 406) under GLP conditions (WoE, 1993). A preliminary test in 4 animals was performed with the test substance at 25, 50 and 75% (w/w) in corn oil in order to determine a non-irritant concentration for topical application in the main assay. Since no primary irritation was observed at any test concentration after 6-h exposure, the undiluted test substance was chosen for both the induction and challenge treatment. In the induction phase, the undiluted test substance was applied to the clipped skin of the left flank of 20 animals using an occlusive dressing. During induction, three consecutive topical applications for a period of 6 h were performed at intervals of 7 days. A control group of 10 animals was treated with corn oil. For challenge exposure on Day 28, the undiluted test substance was applied for 6 h under occlusive conditions to the clipped skin of the right flank of all animals. Skin reactions were evaluated 6, 24, 48 and 72 h after application. None of the treated animals of the test and control group showed any symptoms of dermal irritation after challenge treatment. No test substance-related systemic effects and no effects on body weights were observed in the test or control animals. The regularly performed reliability test with the positive control 1-chloro-2,4-dinitrobenzene

was shown to be valid. Based on the study results, the test material had no skin sensitising effect in guinea pigs.

CAS 97593-30-1

The skin sensitising potential of glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was investigated under GLP conditions in a modified Local Lymph Node Assay (LLNA) in mice according to OECD guideline 429 (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 doses were selected based on available information on the properties of test item. The test substance formulation or the vehicle was 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. 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 sensitizer in the modified LLNA.

Conclusion

The OECD QSAR Toolbox did not predict skin sensitising properties of the target substance. No sensitising potential was seen in experimental studies performed in guinea pigs (Buehler test) and mice (LLNA) with source substances. Based on the available information, glycerol trioctanoate (CAS 538-23-8) is not expected to be skin sensitising.

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 glycerol trioctanoate (CAS 538-23-8), data will be generated from data 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 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.