Registration Dossier

Administrative data

Description of key information

No skin irritation studies on methyl ethyl ketone were identified; however, a skin irritation study on the read across substance s-butanol (structural analogue or surrogate) was identified.  This skin irritation study on s-butanol in rabbits, which was performed according to test guidelines, has demonstrated that the compound is not irritating to rabbit skin.  
Results from the dose-finding study of the skin sensitization study reported in section 7.4.1 shows that MEK did not cause skin irritation in guinea pigs.
Eye irritation studies on methyl ethyl ketone performed across 24 laboratories have demonstrated that the compound is irritating to rabbit eyes.

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:
adverse effect observed (irritating)

Additional information

Skin irritation:

Metabolic data demonstrate that s-butanol is rapidly and extensively converted to methyl ethyl ketone via oxidation of the alcohol functional group by alcohol dehydrogenase in the liver, and potentially in skin as alcohol dehydrogenase is also localized in skin. Thus, methyl ethyl ketone may be used as an appropriate surrogate for s-butanol and vice versa considering that exposure to either substance would essentially result in exposure to methyl ethyl ketone. A skin irritation study on the read-across substance, s-butanol, has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 404 and in compliance with GLP (Price, 1986).  In this study, 3 male and 3 female New Zealand White rabbits were exposed to 0.5 mL of undiluted s-butanol on the shorn dorsal region under semi-occlusive conditions.  Animals were exposed to the test compound for 4 hours and observations were recorded at 4, 24, 48, and 72 hours and 7 days after application. Skin reactions were scored according to a prescribed numerical system. In all animals, no skin reactions were observed following the application of s-butanol to rabbit skin for 4 hours. Based on the results of this study, the authors stated that s-butanol is a non-irritant to rabbit skin. s-Butanol is not classified as a skin irritant according to the CLP classification criteria.

The results from the read-across with SBA are supported with the results from the dose-finding study of the skin sensitization study reported in section 7.4.1, showing that MEK did not cause skin irritation in guinea pigs.

The exposure of the skin to solvents may cause whitening of the skin, and potentially increased transepidermal water loss. Immediate skin whitening has been suggested to correspond to changes in structure and removal of skin lipids. Goldsmith et al. (1988) used an in vitro approach to investigate the effect of methyl ethyl ketone on the structure and removal of lipids from skin. A section of stratum corneum, which was removed from human skin was gently shaken in 5 mL of methyl ethyl ketone for 5 minutes. Lipids were detected from the stratum corneum following thin-layer chromatography. An increase in lipid extraction was observed from the incubation of methyl ethyl ketone and stratum corneum. The authors reported that both whitening of the skin and increased water transport through the skin following exposure to solvents, such as methyl ethyl ketone are due to changes in structure and removal of skin lipids. The results of this study indicate that MEK may extract lipids from the skin potentially causing skin dryness and cracking. Please refer to the document attached to Section 13 for justification of read across.

Eye Irritation:

An eye irritation study on methyl ethyl ketone has been performed in rabbits in a study in which parallel testing on methyl ethyl ketone was performed across 24 laboratories (Weil and Scala, 1971). In this study, the basic Draize method was employed. Specifically, 0.1 mL of undiluted methyl ethyl ketone was instilled into one conjunctival sac (3 right eyes and 3 left eyes) of each of 6 male albino rabbits (strain not reported).  Twenty four hours prior to the test, each eye was treated with 5% solution of sodium fluorescein dye for 20 seconds and then rinsed. Unrinsed eyes were examined for ocular changes at 1, 24, and 72 hours and 7 days after treatment, and scoring was performed according to Draize (1944). There was no reported evidence of corrosivity. The mean overall irritation score was 19.2, 10.8, and 0.8 out of a total possible score of 110 at 1, 3, and 7 days, respectively. As the mean response had recovered close to a score of zero by Day 7, it can be surmised that the reactions would have likely reversed by Day 14. Among 24 laboratories, methyl ethyl ketone was labelled as a non-irritant in 4 labs, as questionable in 3 labs, and as irritant in 17 labs. Methyl ethyl ketone is classified as irritating according to OECD GHS classification criteria.

In another eye irritation study conducted with rabbits (Eye Irritation: Reference chemicals data bank, 1998), undiluted methyl ethyl ketone was instilled into 4 rabbits (strain not reported), and ocular changes were assessed 24, 48, 72 hours and 7 and 10 days after treatment. Ocular changes were scored against the maximum average scoring system of Draize (1944). The modified maximum average scored on Day 1 was 50 out of a possible score of 110. Effects were fully reversed in 10 days. Based on the results of this study, methyl ethyl ketone is considered to be irritating to rabbit eyes. Methyl ethyl ketone is classified as category II (causes serious eye irritation) according to CLP criteria.

Respiratory Irritation:

To examine any sensory or irritant effects of methyl ethyl ketone, human subjects were exposed to methyl ethyl ketone in a simulated workplace environment for a period of 4 hours (Dick et al., 1992). No sensory or irritant effects were reported following single exposures to methyl ethyl ketone at 200 ppm, as assessed from questionnaires.


Effects on eye irritation: irritating

Justification for classification or non-classification

Skin irritation: The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) No. 1272/2008.

Eye irritation: According to CLP classification criteria, this substance does meet the criterial for classification and labelling for this endpoint (category 2: causes serious eye irritation), as set out in Regulation (EC) No. 1272/2008.