N-butyl 4-oxopentanoate

Endpoint summary

Description of key information

Skin irritant

Eye irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation of the substance is experimentally evaluated in vitro according to the OECD Guideline 439 and under GLP conditions. Three tissues of the human skin model EpiDerm were treated with the substance for 60 minutes. The test item was applied directly to each tissue and spread to match the tissue size. DPBS-buffer was used as negative control and 5 % SDS solution was used as positive control. Validity criteria were met.

After the treatment with the test item, the mean value of relative tissue viability was reduced to 30.0 %. This value is below the threshold for skin irritation potential (50 %). The substance is considered at least irritant to skin in the Reconstructed human Epidermis (RhE) Test Method.

Further information are provided by the cross validated prediction of the Acute Dermal Hazard of the substance. As per the prediction, a 64 % probability of Acute Dermal Irritation non-hazard and consequently a 36 % probability of Acute Dermal Irritation hazard are estimated.

Combining the data from both the in vitro study and the (Q)SAR prediction, it can be concluded that the substance is not a Skin Corrosive but it is expected to be a Skin Irritant.

Eye irritation

The eye irritation potential of the substance is evaluated in a Weight of evidence approach.

The potential of the test item to evoke eye irritation was evaluated in a RhCE model in an in vitro study according to the OECD Guideline 492. The test item was applied to a three-dimensional human cornea tissue model in duplicate for an exposure time of 28 minutes. The solid test item was applied to two tissue replicates. After treatment, the respective substance was rinsed from the tissue; then, cell viability of the tissues was evaluated by addition of MTT, which can be reduced to formazan. The formazan production was evaluated by measuring the optical density (OD) of the resulting solution. Concurrent negative (demineralised water) and positive control (methyl acetate) run in parallel. All validity criteria were met. After treatment with the test item, the mean value of relative tissue viability was 57.4 %.This value is well below the threshold for eye hazard potential (≤ 60 %). Under the conditions of the test, the substance is considered either eye irritant or inducing serious eye damage in the EpiOcular^TMEye Irritation Test.

In order to discriminate between the eye irritation and inducing serious eye damage, data from an in vitro experimental study on Similar Substance 02 is also used (Justification for Read Across is given in Section 13 of IUCLID). The corneal damage potential of the substance was assessed by quantitative measurements of changes in opacity and permeability in a bovine cornea, according to the OECD Guideline 437 and EU Method B.47. The test item was brought onto the cornea of a bovine eye which previously had been incubated with cMEM without phenol red at 32 ± 1 °C for 1 hour and whose opacity had been determined. The test item was incubated on the cornea for 10 minutes at 32 ± 1 °C. After removal of the test item and 2 hours post-incubation, opacity and permeability values were measured. The test item was tested neat. Concurrent negative (HBSS) and positive control (DMF) run in parallel Under the conditions of this test, the test item showed effects on the cornea of the bovine eye. The calculated IVIS is 25.45; According to OECD Guideline no. 437, a substance with an IVIS > 3 and ≤ 55 induces effects on the cornea, cannot be classified in an UN GHS Category with the BCOP test only. In this case no prediction can be made.

Considering the results of the two in vitro studies it can be concluded that the substance does not induce serious eye damaga and that is expected to be an Eye irritant.

Justification for classification or non-classification

Skin irritation

Based on the in vitro results (OECD 439) and the validated prediction, the substance is classified as a Skin Irritant (Category 2 -H315) according to the CLP Regulation (EC) No.1272/2008.

Eye irritation

Based on the results of two in vitro studies (OECD 492 and OECD 437) the substance is classified as an Eye Irritant (Category 2 -H319) according to the CLP Regulation (EC) No.1272/2008.