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Description of key information

Information on the acute oral toxicity of methyl ethyl ketone was obtained from data on the read across substance , secondary butanol. Secondary butanol is reported to have low acute oral toxicity following oral administration. Reported oral LD50s of secondary butanol were 2054 mg/kg body weight for males and 2328 mg/kg body weight for females in a study performed similar to test guidelines and in compliance with good laboratory practice. The calculated oral LD50 in rats was 2193 mg/kg body weight. Clinical signs included gait and/or posture abnormalities in all rats at all dose levels. In the higher dose groups some rats were comatose or prostrate within a few hours of dosing, with some animals being unconscious for 24 hours or more. In a supporting study, the oral LD50 for methyl ethyl ketone in female Harlan-Wistar rats is reported to be 3460 mg/kg body weight (Cox, 1976).
The dermal LD50 for methyl ethyl ketone in rabbits was reported by Smyth et al. (1962). As discussed below, the study is lacking details, but is deemed reliable. The dermal LD50 in rabbits is reported to be greater than 10 mL/kg body weight.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
2 193 mg/kg bw

Additional information

Acute Toxicity: Oral

Information on the acute oral toxicity of methyl ethyl ketone was obtained from data on the read across substance, secondary butanol. 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. 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. The potential acute oral toxicity study of secondary butanol was assessed in Fischer 344 rats in a study similar in methodology to OECD Guidelines for the Testing of Chemicals No. 403 and in compliance with Good Laboratory Practice. Groups of 5 males and 5 females were administered undiluted test article via gavage at dose levels of 950, 1200, 1500, 2000, or 2400 mg/kg body weight. Rats were observed for clinical signs over a 14 day observation period and body weights were measured on days 1, 7, and 14. No animals died in the 950 mg/kg body weight group, one animal died in each of the 1200 and 2000 mg/kg body weight groups, two animals died in the 1500 mg/kg body weight group, and eight animals died in the 2400 mg/kg body weight group. All rats at all dose levels had gait and/or posture abnormalities. In the higher dose groups, some rats were comatose or prostrate within a few hours of dosing, with some animals being unconscious for 24 hours or more. All animals had either died or recovered by day 3. All surviving rats had gained weight relative to their body weights by the end of the 14 day observation period. The LD50 for males was calculated to be 2054 mg/kg body weight with 95% confidence intervals of 1283 to 4018 mg/kg body weight. For females, the LD50 was calculated to be 2328 mg/kg body weight with 95% confidence intervals of 1470 to 5428 mg/kg body weight. Finally, the oral LD50 of secondary butanol for males and females was calculated to be 2193 mg/kg body weight with 95% confidence intervals of 1608 to 4146 mg/kg body weight.  

In addition, a supporting study for methyl ethyl ketone is included as a supporting reference. The potential acute oral toxicity of methyl ethyl ketone was assessed in female Harlan-Wistar rats (Cox, 1976). A number of methodology details were not reported; however, rats were administered the test-article by gavage and observed for 14-days for signs of toxicity. The LD50 in female rats was reported to be 4.29 mL/kg body weight. Based on a density of 805.4 g/L, the LD50 was calculated to be 3460 mg/kg body weight. Methyl ethyl ketone was not classified as acutely toxic according to CLP criteria.

Please refer to the document attached to Section 13 for justification of read across.

Acute Toxicity: Dermal

The potential acute dermal toxicity of methyl ethyl ketone was assessed in male New Zealand White rabbits by Smyth et al. (1962). Although this study is lacking in methodological details, the work of this group pre-dates range finding toxicity guidelines and provided much of the basis for their development. Their results are cited by many subsequent authoritative review bodies and are often found in SIDS and SIAR documents via secondary references. Therefore, the results reported by this group are deemed reliable. In their investigation, Smyth et al.(1962) administered the test article to the entire trunk of the 4 male animals for 24 hours with an occlusive plastic film. The

dermal LD50 of methyl ethyl ketone in rabbits was determined to be greater than 10 mL/kg body weight.

Methyl ethyl ketone was not classified as acutely toxic following oral exposure according to CLP.

Acute Toxicity: Inhalation

In accordance with column 2 of REACH Annex VIII, the acute toxicity by inhalation study (required in section 8.5.2) does not need to be conducted as acute toxicity studies are available for the oral and dermal routes of exposure.

Justification for classification or non-classification

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

Specific target organ, Neurotoxicity: According to CLP classification criteria, the substance does meet the criteria for classification and labelling for this endpoint (STOT single exposure category 3, H336 - May cause drowsiness or dizziness), as set out in Regulation (EC) No. 1272/2008.