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Administrative data

Description of key information

Neither classified as a skin or 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)

Additional information

Skin irritation:

Two in vivo studies using rabbits are available for skin irritation. Both studies were on the structurally simliar substance, dibasic esters. One study (Clouzeau, 1987) was of reliability 1 according to Klimisch cotation criteria and was therefore selected as the key study. The other study (Sarver, 1989) was of reliability 2 according to Klimisch cotation criteria and was used as a supporting study. This study was a 24-hour occluded exposure instead of the 4 hours as specified in the current guideline methods. In the key study, no signs of skin irritation (erythema or edema) was observed following a 4-hour semi-occlusive application of the test substance to the shaved skin of 3 rabbits and observation up to 72 hours after the end of application. In the supporting study, the skin reactions were very variable from one rabbit to another. At the 72-hour observation timepoint, one rabbit exhibited severe erythema with fissuring of the skin and slight edema, whereas no to mild erythema was observed in the 5 other animals. One rabbit exhibited no dermal irritation at all throughout the observation period. Considering the mean values for erythema :

Rabbit Nr.

Erythema mean score

1

2.3

2

2.0

3

0.0

4

1.7

5

1.0

6

3.3

Global mean value

1.7

 

the incidence of scores of 2.3 or more was fewer than 4 of 6 animals, and the global mean value over all the animals tested was lower than 2.3. Therefore the results of the supporting study support the absence of classification for skin irritation. No edema was observed except for animal No. 6, which showed slight (score 1) edema 48 hours and 72 hours after exposure.

A third study on dimethyl glutarate did not examine irritation but rather corrosivity. Material was not corrosive.

 

Eye irritation:

Four in vivo studies using rabbits are available for eye irritation: 3 in dibasic esters and one on dimethyl glutarate.

- In the study selected as a key study on the strucutally similar substance, dibasic ester, based on its reliability 1 according to Klimisch cotation criteria (Clouzeau, 1987), moderate conjunctival and chemosis effects were observed in 2 animals one hour after instillation, and only slight conjunctival redness was noted 24 hours after instillation. All effects were fully reversible within 2 days after application. The intensity and duration of the signs of irritation therefore did not warrant any classification.

- In another study considered of reliability 2 according to Klimisch cotation criteria (Valentine, 1993), signs of ocular irritation were observed in 1 out of the 4 rabbits tested. However, a low volume of instillation (10 µL) was used and the observation period was limited to 48 hours after instillation. No reliable conclusion could be made from this study. However, consistently with the key study, no major sign of eye irritation was observed.

- In the third study, considered of reliability 3 according to Klimisch cotation criteria due to the low number of animals used and the low level of details provided regarding the ocular observations (Silber, 1980), signs of irritation were observed in the unwashed eye of a single rabbit, which may have been susceptible. Such data are therefore inappropriate for classification purpose.

Overall, the results of in vivo testing indicate the absence of a need for classification for eye irritation.

-In the fourth study on DMG, the material was found to be slightly irritating. However, the study was not used for classification purposes because only 2 animals were tested and insufficient details were provided regarding the observations and scoring.

Justification for classification or non-classification

The incidence and severity of the signs of irritation observed among those different studies were below the criteria of Annex VI Directive 67/548/EEC or EU Regulation 1272/2008 (CLP), therefore warranting no classification for skin or eye irritation.