Registration Dossier

Administrative data

Description of key information

Based on a combination of in vitro skin sensitisation tests with Isosorbide Monooleate and two in vivo studies with two structural analogues, it can be concluded that Isosorbide Monooleate is not a skin sensitizer.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In vitro

A combination of several in vitro methods addressing key steps of the adverse outcome pathway (AOP) for skin sensitization as defined by OECD, has been conducted to assess the skin sensitizing potential of Isosorbide Monooleate (CAS 28454-96-8). In the test battery evaluation (BASF SE, 2014) a weight of evidence (WoE) approach is used: Any two of the three tests determine the overall results, i.e. any two positive test results drive the prediction of a sensitizer, while any two negative test results drive the prediction of a test substance to be a non-sensitizer.

In a GLP compliant study (BASF SE, 2014), performed similar to OECD guideline 442C, the reactivity of Isosorbide Monooleate towards synthetic cysteine (C)- or lysine (K)- containing peptides was evaluated in the Direct Peptide Reactivity Assay (DPRA). It was concluded that Isosorbide Monooleate shows a minimal chemical reactivity in the DPRA under the test conditions chosen. In a GLP compliant study (BASF SE, 2014), performed similar to the draft OECD h-CLAT guideline, the potential of test substance Isosorbide Monooleateto to induce the cell membrane markers CD86 and CD54 expression was evaluated in the Human Cell Line Activation Test (h-CLAT). The test substance did not induce dendritic cell activation up to the maximum applicable concentration of 1000 μg/mL in the h-CLAT under the test conditions chosen. In a GLP compliant study (BASF SE, 2014), performed similar to OECD guideline 442D, the keratinocyte activating potential of test substance Isosorbide Monooleate was evaluated in the LuSens assay. The test substance did show a keratinocyte activating potential.

In vivo

In vivo data are available for two structural analogues of Isosorbide Monooleate.

In the first study (BASF SE, 2010) Isosorbide (CAS 652-67-5) was used. In this GLP compliant study, performed according to OECD guideline 429, the skin sensitization potential of the test material was assessed in the CBA/Ca strain mouse following topical application to the dorsal surface of the ear. Following a preliminary screening test in which no clinical signs of toxicity were noted at a concentration of 50 % w/w, this concentration was selected as the highest dose investigated in the main test of the Local Lymph Node Assay. Three groups, each of four animals, were treated with 50 μL (25 μL per ear) of the test material as a solution in dimethyl formamide at concentrations of 50 %, 25 % or 10 % w/w. A further group of four animals was treated with dimethyl formamide alone. The stimulation index was determined to be 0.71, 0.55 and 0.55, for the 10, 25 and 50 % (w/w) exposed animals, respectively. All these results were considered negative. The test material was considered to be a non-sensitiser under the conditions of the test.

In the second study (BASF SE, 2008) Isosorbide Diesters (EC 700-073-5) were tested. In this GLP compliant study, performed according to OECD guideline 429, the skin sensitizing potential of the substance was evaluated in the female mouse CBA/J using an in vivo non-radioactive Local Lymph Node Assay. 16 females CBA/J mice were allocated to the following four groups: one vehicle group of four animals receiving the vehicle (acetone / olive oil), one treated group of four animals receiving the test item LAB 3822 at the concentration of 100 %, one vehicle positive group of four animals receiving the vehicle of the positive control substance (acetone), one positive control group of four animals receiving 2,4-dinitrochlorobenzene (DNCB) at the concentration of 0.5 % (w/v) in acetone. Each mouse received a cutaneous application over the dorsal surface of both ears (25 μL) every 24 hours for 3 consecutive days (days 1, 2 and 3). Ear thickness measurements and recording of local reactions were measured before each application and just before euthanasia, in order to assess any possible irritant effect of the test item. Lymphoproliferative response was measured by incorporation of 5-bromo-2’-deoxyuridine on day 6. The results were elucidated using an Elisa system on day 8. Based on a preliminary study the concentration selected for the main study was 100 %. No mortality and no clinical signs were observed during the study. At day 3, a discrete erythema was noted on both ears of one animal and on the left ear of one animal treated with the test item 100 %. The test item did not produce a stimulation index equal to or greater than 3. Consequently, the EC3 value for the test item cannot be calculated.Under the experimental conditions adopted, the test item) did not induce delayed contact hypersensitivity in the murine Local Lymph Node Assay using CBA/J female mice after three consecutive days of treatment.

Conclusion

As two out of three in vitro test with Isosorbide Monooleate were negative the test substance is concluded to be a non-skin sensitizer. In addition, these results are strengthened by the negative in vivo results obtained with two structural analogues of Isorbide Monooleate. Therefore, it is concluded that Isosorbide Monooleate is not sensitizing to the skin.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is not considered to be classified as a skin sensitizer under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.