1H-Imidazole-1-propanenitrile

Endpoint summary

Description of key information

Skin irritation/corrosion (OECD 431, OECD 439): not irritating; reliability score = 1; 2011
Eye irritation (OECD 437, EpiOcular): irritating; reliability score = 1; 2011

Additional information

Skin Irritation

In an in vitro study, performed according to OECD test guidelines 431 and 439 (GLP conditions) for assessment of in vitro skin corrosion and irritation, respectively, a three dimensional human epidermis model (EpiDermTM) was used, which consists of human-derived epidermal keratinocytes cultured to form a multi layered, highly differentiated model of the human epidermis. The skin was treated with the undiluted test substance for 3 min and 1 h (skin corrosion test) and for 1 h with a 24 h post-incubation period (skin irritation test). The skin irritation/corrosion potential is evaluated by a colourimetric assay (MTT-assay) for measuring the induced cytotoxicity. The test is considered positive if the mean tissue viability is less than 50% after 3 min or less than 15% after 1 h treatment in the corrosion test and less than 50% in the irritation test. As the mean tissue viability for the test substance in the irritation test was 96% of the negative control (positive control: 5%), the test substance is not considered irritant to the skin. The mean tissue viability in the corrosion test was 102% and 97% (positive control: 22% and 9%) after treatment for 3 min and 1 h, respectively. Thus, the substance is not considered corrosive (BASF SE, 2011).

The study is suitable for assessment of skin irritation/corrosion as it was performed according to OECD test guidelines and in compliance with the Sequential Testing Strategy for Dermal Irritation and Corrosion suggested in OECD TG 404. In vivo irritancy/corrosion of the test substance is not assumed based on the results of the conducted in vitro tests for corrosion and irritation. No further testing is needed.

   

Eye irritation

An in vitro study performed according to OECD test guideline 437 (GLP conditions) for assessment of eye corrosion / severe irritation in a Bovine Corneal Opacity and Permeability (BCOP-) Test did not reveal any eye corrosion potential of the test substance. 3 corneas were treated for 10 min with 750 µL test substance, negative control or positive control, respectively, followed by a 2 h post-incubation period. Permeability was assessed by measuring the test substance-induced fluorescein permeation through the cornea and corneal opacity was measured by optical density. The obtained values were then used to calculate the In Vitro Irritancy Score (IVIS). The test is considered positive if IVIS ≥ 55. An IVIS of 1.0 was calculated for the test substance (negative control: 0.7; positive control: 61.5). Based on the observed results and applying the evaluation criteria it was concluded that the test substance does not cause serious eye damage in the BCOP Test under the test conditions chosen (BASF SE, 2011).

The study is suitable for assessment of eye irritation as it was performed according to the OECD guideline. The test method, however, does not yet allow for the evaluation of eye irritation as the result does not exclude an irritation potential of the test substance. Therefore, a further in vitro study (GLP conditions) was performed according to a protocol that is currently in the evaluation process. The in vitro test system (EpiOcularTM) is a reconstructed three dimensional human cornea model. 3 cornea models were treated with 50 µL of the test substance, negative control or positive control, each applied for 30 min, respectively, followed by a 2 h post-incubation period. The induced cell damage was measured colourimetrically (MTT assay). The test is considered positive if the mean cell viability is ≤ 50% of the negative control and negative if the mean cell viability is > 60%. The mean cell viability of the test substance treated corneas was 50% (positive control: 15%). Based on the observed results and applying the evaluation criteria it was concluded that the test substance causes irritation in the EpiOcularTM Test under the test conditions chosen (BASF SE, 2011).

The study is suitable for assessment of eye irritation as it was performed to an accepted protocol currently being in the evaluation process. Based on this result and the result of another valid in vitro eye irritation test (BCOP test), classification for eye irritation is needed according to CLP, GHS (UN). Discrimination betwenn category 2A ans 2B is not possible with in vitro testing.

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 the purpose of classification. Based on the criteria laid down in Regulation (EC) No. 1272/2008, as amended for the 2nd time in Directive EC 286/2011, category 2 is warranted due to its eye irritation potential. Classification for skin irritation is not warranted.

Regarding the impurities acrylonitril (1.5%) and imidazole (1.5%), classification for skin and eye irritation is warranted as "category 2" and "category 1", respectively.