Isooctadecanoic acid, monoester with propane-1,2-diol

Endpoint summary

Description of key information

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

 

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

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

Reason / purpose for cross-reference:

read-across source

Key result

Parameter:

SI

Value:

0.98

Test group / Remarks:

25% test substance

Key result

Parameter:

SI

Value:

1.02

Test group / Remarks:

50% test substance

Key result

Parameter:

SI

Value:

1.32

Test group / Remarks:

100% test substance

Key result

Parameter:

SI

Value:

1.13

Test group / Remarks:

5% positive control substance

Key result

Parameter:

SI

Value:

1.48

Test group / Remarks:

10% positive control substance

Key result

Parameter:

SI

Value:

2.19

Test group / Remarks:

25% positive control substance

Key result

Parameter:

other: EC1.4 [%]

Test group / Remarks:

test substance groups

Remarks on result:

not determinable

Remarks:

as all SI values were < 1.4. The cut-off value 1.4 was validated in the laboratory.

Key result

Parameter:

other: EC1.4 [%]

Value:

8.86

Test group / Remarks:

positive control groups

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

Additional in vivo skin sensitization data (GPMT) was available for two source substances.

In a Guinea pig maximisation study performed with Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3) according to EU Method B.6 under GLP conditions challenge treatment was performed by topical application of the test substance at 2.5% and 5% (highest non-irritant concentration) to animals for 24 h, under semi-occlusive conditions. No sensitising effect was observed.

In another Guinea pig maximisation study with 1,2-Propandiol-mono/di-dodecanoate (CAS 37321-62-3) according to OECD guideline 406 under GLP conditions challenge treatment was performed by topical application of the undiluted test substance to animals for 24 hours under occlusive conditions. No sensitising effect in was observed.

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 sensitising potential. In a LLNA with the source substance Fatty acids, vegetable-oil, esters with dipropylene glycol (CAS 95009-41-9) no skin sensitising effect was found. In two guinea pig maximisation tests with the source substances Dodecanoic acid, ester with 1,2-propandiol (CAS 37321-62-3) and 2-hydroxypropyl myristate (CAS 29059-24-3) no skin sensitising potential was found. Therefore, no skin sensitising potential is expected for target substance isooctadecanoic acid, monoester with propane-1,2-diol (CAS 68171-38-0).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

 

Skin sensitisation

CAS 95009-41 -9

A LLNA assay was performed according to OECD guideline 429 under GLP conditions with Fatty acids, vegetable-oil, esters with dipropylene glycol (CAS 95009-41-9) in mice. 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 1,2-Propandiol-mono/di-dodecanoate (CAS 37321-62-3) according to OECD guideline 406 and under GLP conditions (WoE, 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.

CAS 29059-24-3

A Guinea pig maximisation study was performed with Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3) according to EU Method B.6 and under GLP conditions (WoE, 1989). 20 test and 20 control Pirbright white guinea pigs were induced on Day 0 intradermally with 0.1% of the test substance in paraffin oil with and without Freud's complete adjuvant. After intradermal induction all animals showed the characteristic reactions after application of FCA (Freund´s complete adjuvant). The test substance without FCA caused moderate skin reactions which were of a lower grade than the reactions caused by FCA alone or by the solution of FCA with the test substance. On Day 7, a 48 -hour epicutaneous induction treatment with 15% test substance in paraffin oil was done under occlusive conditions. On Day 21, the challenge treatment was performed by topical application of the test substance at 2.5% and 5% (highest non-irritant concentration) to all animals for 24 h, under semi-occlusive conditions. Skin reactions were evaluated 24 and 48 hour after the end of challenge exposure; none of the test animals and 1/20 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

When entering the CAS number 68171-38-0 into the OECD QSAR Toolbox v4.1, 2017 and profiling for protein binding (general mechanistic and skin sensitization endpoint specific) no alert was found.

No sensitising potential was seen in experimental studies in guinea pigs performed with analogue substances. Based on the available information, Isooctadecanoic acid, monoester with propane-1,2 -diol (CAS 68171 -38 -0) 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 Isooctadecanoic acid, monoester with propane-1,2-diol (CAS 68171-38-0), 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.