Registration Dossier

Diss Factsheets

Administrative data

Description of key information

In vivo (read-across, LLNA, according to OECD guideline 429): not sensitising

In vivo (read across, GPMT, according to OECD guideline 406): not sensitising

QSAR prediction: not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (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
Parameter:
SI
Value:
1
Test group / Remarks:
Control
Remarks on result:
other:
Remarks:
Source: CAS 3687-46-5
Key result
Parameter:
SI
Value:
1.2
Test group / Remarks:
25%
Remarks on result:
other:
Remarks:
Source: CAS 3687-46-5
Key result
Parameter:
SI
Value:
2
Test group / Remarks:
50%
Remarks on result:
other:
Remarks:
Source: CAS 3687-46-5
Key result
Parameter:
SI
Value:
2.1
Test group / Remarks:
100%
Remarks on result:
other:
Remarks:
Source: CAS 3687-46-5
Cellular proliferation data / Observations:
The mean DPM values for the control, 25, 50 and 100% groups were 488, 571, 951 and 1013, respectively. The slight increase in DPM with increasing dose level was not statistically significant. (Source: CAS 3687-46-5)

In vivo skin sensitisation data from the source substance decyl oleate (CAS 3687-46-5) was selected as key result for reasons of data reliability and structural similarity. Additional in vivo data on skin sensitisation was available for the source substance 2-octyldodecyl isooctadecanoate (CAS 93803-87-3): No indication of skin sensitisation was found in a Guinea pig maximisation test (GPMT) with guinea pigs. No skin reactions were observed after the topical challenge treatment with the undiluted test substance in any of the animals of the test (n=10) and control (n=5) groups.

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 Local Lymph Node Assay performed in mice with the source substance decyl oleate (CAS 3687-46-5) no indication for skin sensitisation was found. In a guinea pig maximisation test (GPMT) performed with the source substance 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) no skin sensitisation was observed following semi-occlusive epicutaneous challenge. Therefore, no skin sensitisation potential is expected for target substance Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS).
Endpoint:
skin sensitisation, other
Remarks:
: QSAR skin sensitisation 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
The OECD QSAR Toolbox v4.2 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 4.2

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

4. SCIENTIFIC VALIDITY OF THE (Q)SAR MODEL
The application was developed in line with the OECD principles for QSAR models by the Laboratory of Mathematical Chemistry (https://www.qsartoolbox.org/about). The OECD QSAR Toolbox development is overseen by the OECD QSAR Application Toolbox Management Group under supervision of the OECD Task Force on Hazard Assessment of the OECD Chemicals Committee. Stakeholders from member countries, ECHA chemical industry and NGOs participate in the work of the QSAR Application Toolbox Management Group.
5. APPLICABILITY DOMAIN
For each of the profilers, structural alerts were identified using experimental data. A description of how a profile was built and data sources used to derive structural boundaries is given per profiler in the OECD QSAR Toolbox. For each profiler, a warning is given if the test chemical does not fall within the applicability domain. For the relevant profilers, all the representative constituents of the test chemical fell within the relevant applicability domain.

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 QSAR
Principles of method if other than guideline:
- Principle of test: The OECD QSAR Toolbox v4.2 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 were negative for skin sensitising potential, based on QSAR prediction (OECD QSAR Toolbox v4.2, ECHA database).
Conclusions:
Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS) is not expected to have a skin sensitising potential.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Justification for read-across

There are no in vitro or in vivo data on the skin sensitisation potential of Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS). The assessment was therefore performed as a weight-of-evidence approach based on QSAR modelling and studies performed 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).

QSAR prediction

The skin sensitising potential of 4 representative constituents Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS) was predicted using relevant profilers in the OECD QSAR Toolbox v4.2 (WoE, 2018). The test substance falls within the applicability domain for the endpoint specific profilers on protein binding for skin sensitisation and for general mechanistic profilers for protein binding. The result of the profiling predictions was negative, no skin sensitising potential for Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS) was predicted.

Animal data

CAS 3687-46-5

An in vivo skin sensitisation study (Local Lymph Node Assay, LLNA) was performed with Decyl oleate (CAS 3687-46-5) according to OECD guideline 429 and under GLP conditions (WoE, 2010). Five female CBA/J mice per dose were treated with 0, 25, 50 and 100% of the test substance in acetone/olive oil. The test substance formulations or the vehicle were applied topically onto the dorsal part of each ear (25 µL/ear) for three consecutive days. All mice were sacrificed three days after the last treatment (on Day 6) and the weight of the lymph nodes was determined. The cell proliferation of pooled lymph nodes from individual animals was measured as 3H-methyl thymidine incorporation and determined by beta-scintillation counting. The stimulation indices were 1.0, 1.2, 2.0 and 2.1 for the control, 25, 50 and 100% groups respectively. The SI slightly increased with the dose level, but not statistically significant. Positive and vehicle controls were valid. An EC3 value of the test substance could not be calculated, as all stimulation indices were <3. Based on the study results, the test substance was not skin sensitising.

CAS 93803-87-3

A Guinea pig maximisation test (GPMT) was performed with 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) under GLP conditions according to OECD guideline 406 (WoE, 1998). 10 test and 5 control Himalayan guinea pigs were induced intradermally with undiluted test substance on both sides of the spine with and without Freud's complete adjuvant. On Day 7, the animals were treated with 10% sodium dodecyl sulfate to induce mild skin irritation. On Day 8, a 48-h epicutaneous induction treatment with the undiluted test substance was performed under semi-occlusive conditions. On Day 22, the challenge treatment was performed by topical application of the test substance at 100% (right flank) and a blank patch (left flank) to all animals for 24 h, under semi-occlusive conditions. 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. 8 h after intradermal induction, slight to severe erythema was noted at all of the sites injected with FCA/water and FCA/test substance in 10/10 treated and 5/5 control animals. 4/5 control animals also exhibited necrosis at the FCA/test substance injection site. In 3/10 treated animals slight to well-defined erythema was observed at the injection site of the test substance. Following the topical induction, severe erythema and scabs were observed at the test site in 3/10 treated animals. A further 4/10 (in total 7/10) treated and 4/5 control animals exhibited only scabs. No skin reactions were observed after the challenge treatment in any of the animals of the test and control groups. The results of the reliability check carried out at regular intervals were positive, confirming the reliability of the assay. Based on the results, the test substance had no sensitising effect in guinea pigs under the experimental conditions.

Overall conclusion for skin sensitisation

The OECD QSAR Toolbox profiling results did not predict skin sensitising properties of the target substance. No sensitising potential was seen in experimental studies in mice (LLNA) and guinea pigs (GPMT) performed with source substances. Based on the available information, the target substance Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS) 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". By applying the analogue concept to Fatty acids, C16, C18 and C18-unsaturated, C12-15 alcohol (linear and branched), esters (no CAS) 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.