Registration Dossier

Administrative data

Description of key information

Isosorbide Monooleate does not show a skin and eye irritation potential in the EpiDerm™ skin irritation test and EpiOcular™  eye irritation test, respectively. The in vivo studies performed with structural analogues indicated that the Isosorbide Monooleate is also not skin corrosive or eye damaging.

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

In a GLP compliant study (BASF SE, 2014), performed according to OECD guideline 439, the potential of Isosorbide Monooleate (CAS 28454-96-8) to cause dermal irritation was assessed by a single topical application of 30 μL of the undiluted test substance to a reconstructed three dimensional human epidermis model (EpiDerm™). For better handling the solid test substance was heated shortly at ca. 50 °C. Before application the test substance was cooled down to room temperature. Three EpiDerm™ tissue samples were incubated with the test substance for 1 hour followed by a 42-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/ post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues was compared to that of negative control tissues. The quotient of both values indicated the relative tissue viability. The EpiDerm skin irritation test showed that the test substance is able to reduce MTT directly. However, this ability of direct MTT reduction did not impair the study result as demonstrated by the concurrently performed exposure of control tissues inactivated by freezing (KC). The mean viability of the test-substance treated tissues determined after an exposure period of 1 hour with about 42 hours post-incubation was 115 %. Based on the observed results and applying the evaluation criteria it was concluded, that Isosorbide Monooleate does not show a skin irritation potential in the EpiDerm™ skin irritation test under the test conditions chosen.

In a GLP compliant study (BASF SE, 2001), performed according to OECD guideline 404, the skin irritating potential of a structural analogue of Isosorbide Monooleate was evaluated by a single topical application of 0.5 mg of the undiluted substance. Six New Zealand White rabbits were exposed to Isosorbide (CAS 652-67-5) for 23 hours, using a patch of 4 cm2 with a semi-occlusive dressing. The cutaneous reactions were assessed 1 hour after removal of the patch and approximately 24 and 48 hours later. As no skin reactions were observed from 24 to 48 hours the test was terminated after 48 hours of evaluation. No edema or eryhema were observed at the 1, 24, and 48 hour time point. The test substance was not considered to be a skin irritant under the conditions of this test.

Based on this combined information Isosorbide Monooleate (CAS 28454-96-8) is not considered to be irritating to the skin.

 

Eye irritation

In a GLP compliant study (BASF SE, 2014) the eye irritating potential of Isosorbide Monooleate (CAS 28454-96-8) was evaluated. The potential of Isosorbide Monooleate to cause ocular irritation was assessed by a single topical application of 50 μL of the undiluted test substance to a reconstructed three dimensional human cornea model (EpiOcular™). For better handling the solid test substance was heated shortly at about 50 °C. Before application the test substance was cooled down to room temperature. Two EpiOcular™ tissue samples were incubated with the test substance for 30 minutes followed by a 2-hours post-incubation period. Tissue destruction was determined by measuring the metabolic activity of the tissue after exposure/post-incubation using a colorimetric test. The reduction of mitochondrial dehydrogenase activity, measured by reduced formazan production after incubation with a tetrazolium salt (MTT) was chosen as endpoint. The formazan production of the test substance treated epidermal tissues is compared to that of negative control tissues. The ratio of the values indicates the relative tissue viability. The EpiOcular™ eye irritation test showed that the test substance is able to reduce MTT directly. However, this ability of direct MTT reduction did not impair the study result as demonstrated by the concurrently performed exposure of control tissues inactivated by freezing. The mean viability of the test substance treated tissues was 94 %. Based on the observed results for the EpiOcular Test it was concluded, that Isosorbide Monooleate does not show an eye irritation potential under the test conditions chosen.

Two eye irritating studies are performed with two structural analogues of Isosorbide Monooleate (CAS 28454-96-8). In the first study (BASF SE, 2001), Isosorbide (CAS 652-67-5) was used. In this GLP compliant study, performed according to OECD guideline 405, 6 New Zealand White rabbits received 0.1 g of the test substance to the conjunctival sac of the right eye. The untreated left eye served as a control. Ophthalmologic examination of each eye of each animal was realized 1 hour, 2 days, 3 days, 4 days and 7 days after instillation.The mean score (24 to 72 hours) for irritation was calculated to be 0 for corneal opacity, iritis, conjunctival redness and chemosis. The substance was therefore not considered to be irritating to the eyes. In the second study (BASF SE, 2008), Isosorbide Diesters (EC 700-073-5) was tested. In this GLP compliant study, performed according to OECD guideline 405, three New Zealand White rabbits received 0.1 mL of the test substance to the conjunctival sac of the left eye. The untreated right eye served as a control. Any conjunctival, iris and corneal lesion was evaluated approximately one hour, then on days 2, 3, 4, 5 and 8 after instillation of the test substance. The mean score (24 to 72 hours) for irritation was calculated to be 0 for corneal opacity, iritis and chemosis. The mean score (24 to 72 hours) for conjunctival redness was calculated to be 1, 1, and 1.7 for animal 1, 2, and 3, respectively. The test substance was therefore not considered to be irritating to the eyes.

Based on this combined information Isosorbide Monooleate (CAS 28454-96-8) is not considered to be irritating to the eyes.

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 for skin corrosion/irritation to skin and eye damage/irritation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.