Ethyl 3-(2,4-dimethyl-1,3-dioxolan-2-yl)propanoate

Endpoint summary

Description of key information

non-skin irritant

non-eye irritant

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

The in-vitro skin irritation potential of the test substance was determined using the EpiDermTMskin model based on the colorimetric MTT viability assay. The skin tissue cultures were tested in duplicate with the test substance at four exposure times of 1, 4, 8 and 24 h. The exposure time of the positive control was also exposed in duplicate for 4 and 8 h. The ET50 for the test substance was established to be 2.8 h. The tissue viability after 1, 4, 8 and 24 hours was 75.1, 33.8, 8.2 and 7.7 % respectively.

Based on the classification established by MatTek Corporation (2005), the test substance can be considered as a moderate skin irritant in the MTT time course assay. However, besides the ET50 available, the determined tissue viabilities can be used for the evaluation of the skin irritation potential of the substance. The study followed a procedure similarly to the one of OECD 431 (2004), thus, according to the OECD 431 (2004) criteria, a viability of 75.1 % after 1 hour suggests that the substance is not a skin corrosive.

Eye irritation

The substance was evaluated for its potential to cause ocular irritancy to isolated bovine corneas in-vitro, as measured by the test article’s ability to induce opacity and permeability to fluorescein (relative to the control corneas). During the study the in vitro score (IVIS) is determined. Bovine corneas obtained from freshly slaughtered animals, were mounted in special holders and exposed to the test articles. Five corneas were treated with the test article and three corneas were each treated by the positive and negative control. The corneas were incubated at 32 ± 1 °C for 10 minutes and the epithelial side was washed at least three times with Complete MEM (containing phenol red) to ensure total removal of test article or control and then finally rinsed with Complete MEM (without phenol red). An opacity measurement was taken and then the corneas were returned to the anterior chambers refilled with fresh Complete MEM (without phenol red) and incubated for approximately 2 hours before a final opacity measurement was taken. The posterior chamber was filled with fresh Complete MEM and fluorescein solution was added to the anterior chamber and incubated at 32 ± 1 °C for 90 minutes and then aliquots were taken from the posterior chambers and the OD490 value was measured. The permeability measurement and in vitro score was then calculated. The test substance produced an in IVIS of 6.1, as measured by changes in opacity and permeability, which classifies it as a mild irritant to bovine corneas, based on the classification system established by Sina et al. The guideline followed was similar to the one of OECD Guideline 437 (2009) and thus based on its classification criteria, the IVIS Score obtained does not permit any prediction to be made since is lower than the corrosivity threshold 55.1. For this reason, a further in-vivo study on Similar Substance 1 is taken into account (Justification for Read Across is given in Section 13 of IUCLID).

The possible irritation or corrosion potential of the similar substance to the eyes of the rabbits was evaluated according to the OECD Guideline 405, EU Method B.5, EPA OPPTS 870.2400 and the Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF). The study was performed in a stepwise manner and was started by the treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner 5 days later, after considering the degree of eye irritation observed in the first animal. Each animal was treated by instillation of 0.1 ml of the test substance, in the conjunctival sac of one of the eyes; the other eye remained untreated and served as the reference control. Immediately after the 24-hour observation, a solution of fluorescein was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance. Instillation of the test substance resulted in conjunctival irritation of two of the three rabbits, indicated by redness and/or discharge, which completely resolved 24 hours after instillation in both animals. No iridial irritation, corneal opacity or systemic toxicity were observed. The treatment of eyes with 2 % fluorescein 24 hours after the test substance instillation revealed no corneal epithelial damage. No staining of (peri) ocular tissues by the test substance was observed and no test substance remnants were seen. Based on the scores obtained for iris, cornea and conjuctivae, the substance is not an eye irritant. 

The BCOP test method has an overall accuracy of 79 % (113/143) to 81 % (119/147), a false positive rate of 19 % (20/103) to 21 % (22/103), and a false negative rate of 16 % (7/43) to 25 % (10/40), when compared to in vivo rabbit eye test method data classified according to the EPA, EU, or GHS classification systems. In the range between 0 to 55.1 (IVIS) no prediction can be made and therefore in this range the non-irritant, the irritant and some false negative corrosive substances could be found. Obtaining an IVIS score of 6.1 which is quite lower than the (corrosivity) threshold and by considering the negative in-vivo result of the similar substance it could be concluded that the substance is not an eye-irritant.

Justification for classification or non-classification

Skin irritation

The evaluation for the classification or non-classification of the substance was based on the results of the in-vitro study on the substance.

According to the OECD 431 (2004):

The test substance is considered to be corrosive to skin:

i) if the viability after 3 minutes exposure is less than 50 %, or ii) if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15 %.

The test substance is considered to be non-corrosive to skin:

i) if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is greater than or equal to 15 %.

Considering the viability values obtained, the viabiliy after one hour is 75.1 % and thus more than the threshold indicated. No information is available for the viability after 3 minutes but it is expected to be higher than the one obtained after 1 hour due to the fact that the viability seems to decrease over time. This suggests that the substance is not corrosive but it does not exclude the possibility to be irritant. However, all the other available data on the substance: the substance did not produce any irritation effects during the acute dermal toxicity study and the HPRT study nor is a skin sensitiser, suggest that the substance is not expected to be a skin-irritant. It is therefore not classified for skin irritation according to the CLP Regulation (EC) No. 1272/2008.

Eye irritation

The evaluation for the classification or non-classification of the substance was based on the results one in-vitro and one in-vivo study.

The results of the in-vitro study do not permit any prediction to be made besides the one that the substance is not corrosive or severely irritant. In combination with the results of the in-vivo study which was found negative, the substance is not classified as an eye irritant according to the CLP Regulation (EC) No. 1272/2008.