Registration Dossier

Administrative data

Description of key information

Skin sensitisation (Read-across, LLNA, OECD 429): not sensitising

Skin sensitisation (Read-across, GPMT, OECD 406): not sensitising

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
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:
key study
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:
0.98
Variability:
cells counted per group
Test group / Remarks:
25% test substance
Key result
Parameter:
SI
Value:
1.02
Variability:
cells counted per group
Test group / Remarks:
50% test substance
Key result
Parameter:
SI
Value:
1.32
Variability:
cells counted per group
Test group / Remarks:
100% test substance
Key result
Parameter:
SI
Value:
1.13
Variability:
cells counted per group
Test group / Remarks:
5% positive control substance
Key result
Parameter:
SI
Value:
1.48
Variability:
cells counted per group
Test group / Remarks:
10% positive control substance
Key result
Parameter:
SI
Value:
2.19
Variability:
cells counted per group
Test group / Remarks:
25% positive control substance
Key result
Parameter:
other: EC1.4 [%]
Value:
8.86
Variability:
cells were counted per group (n=4 mice)
Test group / Remarks:
positive control substance
Remarks on result:
other: EC1.4 was treshold in this study
Key result
Parameter:
other: EC1.4 [%]
Variability:
cells were counted per group (n=4 mice)
Test group / Remarks:
test substance
Remarks on result:
not determinable
Remarks:
as all SI values were < 1.4

Data from the source substance Fatty acids, vegetable-oil, esters with dipropylene glycol (CAS 95009-41-9) was selected as key results for reasons of structural similarity and data reliability.

Additional data from an guinea pig maximisation test is given for the source substance 1,2-Propandiol-mono/di-dodecanoate (CAS 37321-62-3). No indication of skin sensitisation was observed after topical challenge treatment at 100% (highest non-irritant concentration) for 24 hours under occlusive conditions. Skin reactions were evaluated 24 and 48 hours after the end of challenge exposure; none of the test animals and none of the control animals showed a skin reaction at the 48 and 72 hour post application readings.

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 LLNA assay with C8-10 Fatty acids, vegetable-oil, esters with dipropylene glycol (CAS 95009-41-9) no indication for sensitisation was found. In a guinea pig maximisation test with Dodecanoic acid, ester with 1,2-propandiol (CAS 37321-62-3) no skin sensitising potential was found. Therefore, no skin sensitisation potential is expected for the target substance Propylene dinonanoate (CAS 41395-83-9).
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Read-across justification

There are no data on the skin sensitisation potential of Propylene dinonanoate (CAS 41395-83-9). The assessment was therefore based on studies conducted with analogue 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

CAS 95009-41-9

A LLNA assay was performed according to OECD guideline 429 under GLP conditions with C8-C10 Fatty acids, vegetable-oil, esters with dipropylene glycol (CAS 95009-41-9) in mice (key study, 2014). Groups of 4 mice were treated by topical applications to the dorsal surface of the ears for three consecutive days with 50 μL (25 μL per ear) of the test item at 0% (vehicle control), 25%, 50% and 100%. On day 6, the proliferation of lymphocytes in the draining auricular lymph nodes was determined by cell counting. No mortality and no signs of systemic toxicity were noted in the test and control animals during the test. No skin irritation was recorded at any of the concentrations used during the test. No significant increase in ear thickness and in ear weight was noted in animals treated at 25%, 50% and 100%. The Stimulation Index (SI) was 0.98, 1.02 and 1.32 for the treated groups at 25%, 50% and 100%, respectively. The Stimulation Index (SI) was 1.13, 1.48 and 2.19 for the positive control groups at 5%, 10% and 25% hexyl cinnamic aldehyde, respectively. For interpretation of the results a cut-off value of EC 1.4 was used, which had been validated in the laboratory as alternative endpoint value instead of EC3. For the test groups no EC1.4 could be calculated as all SI values were < 1.4. Under the conditions of the study, the test item was not considered as skin sensitising.

CAS 37321-62-3

A Guinea pig maximisation study was performed with Dodecanoic acid, ester with 1,2-propandiol (CAS 37321-62-3) according to OECD guideline 406 and under GLP conditions (supporting study, 1992). 19 test and 10 control Dunkin Hartley guinea pigs were induced on Day 0 intradermally with 10% of the test substance in corn oil with and without Freud's complete adjuvant. One hour after injection of FCA all test and control animals showed severe erythema and oedema. 11/20 test animals and 6/20 control animals showed injuries in the depth. 24 hours later all animals showed severe erythema and oedema. 24 hours after test substance injection all test animals showed slight erythema and oedema comparable to the control animals. Injection of test substance and FCA (1:1) induced moderate to strong erythema and moderate oedema. After 24 hours strong erythema with deep injuries in 8/20 test animals and strong oedema were observed. Control animals injected with 50% FCA and corn oil showed 1 hour after application well defined erythema and slight oedema. 24 hours post application severe erythema with deep injuries (3/20) and strong oedema were observed. On Day 6, the animals were treated with 10% sodium dodecyl sulfate to induce mild skin irritation. On Day 7, a 48-hour epicutaneous induction treatment with the undiluted test substance was done under occlusive conditions. One animal died within 24 hours after the dermal induction. Possibly, the animal was too strong bandaged resulting in dyspnoea and death. Necropsy revealed a clear yellow liquid in the thorax and no further abnormal organ findings. On Day 21, the challenge treatment was performed by topical application of the test substance at 100% (highest non-irritant concentration) to all animals for 24 hours, under occlusive conditions. Skin reactions were evaluated 24 and 48 hours after the end of challenge exposure; none of the test animals and none of the control animals showed a skin reaction at the 48 and 72 hour post application readings. No positive control group was included. Based on the study conditions, the test substance had no sensitising effect in guinea pigs.

Overall conclusion for skin sensitisation

No sensitising potential was seen in experimental studies in mice and guinea pigs performed with analogue source substances. Based on the available information, Propylene dinonanoate (41395-83-9) 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 Propylene dinonanoate (41395-83-9), 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.