Registration Dossier

Administrative data

Description of key information

Skin irritation: Not irritating (Two reliable studies)

Eye irritation: not irritating (One reliable study reported across a number of publications)

Ethyl acetate vapor is a weak sensory irritant at high concentrations.  Liquid ethyl acetate is mildly irritating to the eye and is not a skin 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

In a briefly reported study carried out to a US Federal Register protocol, rabbits were dermally exposed to ethyl acetate under semi-occlusive conditions for a period of 4 hours. No signs of any irritation were observed during the 72 hour observation period after the exposure. Under the conditions of this study, ethyl acetate was clearly not a skin irritant. A study to examine ethyl acetate as a permeation enhancer solvent for transdermal drug delivery reported mild to moderate irritation to rabbit skin following application of a transdermal drug delivery device containing the drug levonorgestrel and neat ethyl acetate. Control devices containing only water were also found to be mildly irritating. Some residual irritancy may have been caused by adhesive remaining on the skin following test cell removal or the semi-permeable membrane used in the device. Whilst the solvent was not in direct contact with the skin (separated by the 50um membrane), the duration of exposure was significantly longer than required for a guideline study. This study is deemed sufficiently reliable to characterise ethyl acetate as not significantly irritating to the skin. Ethyl acetate does not appear to be irritating to the skin when studied using classical animal assays.

In a reliable guideline eye irritancy test, the irritant properties of ethyl acetate were assessed by quantifying the irritancy effects in vivo by measuring the degree of corneal swelling induced following instillation of 0.1ml of material to rabbit eyes. The raw data from this study is available in a secondary source publication. In the published version of the study, corneal thickness was reported before instillation and thereafter at intervals coincident with the more usual Draize scoring if conjunctival, iris and corneal effects. Results were expressed as swelling:corneal thickness on observed day / corneal thickness prior to instillation x 100. Based on all the substances studied, a significant linear correlation was established between Draize score and % swelling and using data from this and a similar study a threshold figure of 60% swelling (ie a result of 160%) can be set for classification as an irritant. The corneal swelling of pure ethyl acetate was only 6% (result =106%) confirming minimal irritation. Indeed the authors rated it only as a mild eye irritant. Other available data is either not reliable or not rated for its reliability but is consistent with a low irritation potential.

Justification for classification or non-classification

Ethyl acetate does not meet the criteria for classification either as an eye or a skin irritant according to the criteria of directive 67/548 or regulation 1272/2008. Based on the known defatting properties of solvents with physicochemical properties such as ethyl acetate and some evidence of irritation from the longer duration exposure of Friend, a classification for repeated exposure causing skin dryness or cracking does seem appropriate.