Lauric acid, ester with hydroxypropanediyl diacetate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Analogue justification 

There are no available data on the skin sensitisation potential of Lauric acid ester with hydroxypropanediyl diacetate (CAS 30899-62-8). 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 30899-62-8

The potential for the C12/C2/C2 component of Lauric acid ester with hydroxypropanediyl diacetate to be skin sensitisers was predicted in the QSAR OECD Toolbox (Nordheim, 2016). The result for the component is considered to be representative of the target substance. There was no alert for skin sensitisation potential, estimated based on protein binding potential, in the database OASIS v1.3 (Protein binding alerts for skin sensitization).

Animal data

CAS 97593-30-1

The skin sensitising potential of Glycerides, C8-21 and C8-21-unsatd., mono- and di-, acetates was investigated in a modified Local Lymph Node Assay (LLNA) in mice performed according to OECD guideline 429 and in compliance with GLP (Vohr, 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 test substance formulations or the vehicle were 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 at necropsy. 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 sensitiser in the modified LLNA.

CAS 736150-63-3

The skin sensitising potential of Glycerides, castor-oil mono, hydrogenated, acetates was investigated in a Local Lymph Node Assay (LLNA) in mice performed according to OECD guideline 429 and in compliance with GLP (Meurer, 2007). 25 µl of a 10, 20 and 50% in dimethyl sulphoxide, or vehicle alone, was applied to the dorsal surface of both ears of 5 CBA7CaOlaHsd mice/dose for 3 consecutive days. On Day 6, each animal was injected via the tail vein with 0.25 mL sterile phosphate buffered saline containing 20.2 µCi of 3H-methyl thymidine. After approximately 5 hours, the mice were sacrificed and the draining lymph nodes of the ears were excised. The nodes were pooled for each animal in PBS and the DNA precipitated with 5% TCA at 4 °C for at least 18 h. The positive control group (hexyl cinnamic aldehyde) was valid. None of the animals treated with Batch B, C and D showed clinical signs during the course of the study. The animals treated with 25% and 50% of Batch A showed a reddening of the ear skin from the second day of treatment. This is not considered to have had a significant effect on the activity of the lymph nodes. At the concentration of 50% of Batch A, a statistically significant difference of DPM per animal was observed (p ≤ 0.05). The other test groups did not show a statistically significant different response from the vehicle control. The effects observed for Batch A seemed to be dose-dependent. The effects observed for Batch B and D seemed to be dose-dependent but this was not confirmed by statistical analysis. The effects seen for Batch C were not dose-dependent. The stimulation indices of 0.97 in the 10% groups, 1.53 in the 25% groups and 1.86 in the 50% groups were observed. At a concentration of 50% of Batch A, a statistically significant difference of DPM per animal was observed (p ≤ 0.05), however, the stimulation index (S.I.) was 1.71. EC3 values of the test groups could not be calculated, since none of the tested concentrations induced a S.I. greater than 3. Therefore the test substance is considered to be not skin sensitising.

Overall conclusion for skin sensitisation

A weight-of-evidence approach was applied to assess the skin sensitising potential of the target substance Lauric acid ester with hydroxypropanediyl diacetate. The OECD QSAR Toolbox did not predict protein binding indicative for sensitising properties by the C12/C2/C2 component of Lauric acid ester with hydroxypropanediyl diacetate. The LLNA studies performed with two source substances were negative. Taking into account the available information, Lauric acid ester with hydroxypropanediyl diacetate is not expected to be skin sensitising.

Migrated from Short description of key information:
Skin sensitisation (LLNA, modified LLNA, QSAR): not sensitising

Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted by means of read-across from structural analogues combined with QSAR analysis for the target substance. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between the source and target substance and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

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 Lauric acid ester with hydroxypropanediyl diacetate (CAS 30899-62-8), data will be generated from reference source substance(s) and QSAR predictions 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 combined with QSAR analyses performed with the main component, 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.