Registration Dossier

Administrative data

Description of key information

In a 90-day inhalation study in Fischer 344 rats, animals were exposed to methyl ethyl ketone (MEK) concentrations at 0 (control), 1254 ppm, 2518 ppm, or 5041 ppm for 6 hours/day, 5 days/week for 89 or 90 consecutive days.  This GLP study was equivalent to OECD Test Guideline 413. Although a NOEC was not determined by study authors, based on the data a NOAEC of 5014 ppm can be considered for subchronic inhalation toxicity given that the effects noted in both sexes at 5014 ppm were limited to non specific effects including decreased body weight and increased absolute liver weights and liver to body weight ratios. Supportive studies for MEK were not located.  Dermal and oral studies have not been conducted. 

Key value for chemical safety assessment

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
14 871 mg/m³

Additional information

In a whole body 90-day inhalation study in Fischer 344 rats, animals were exposed to methyl ethyl ketone at concentrations of 0 (control), 1254 ppm, 2518 ppm, or 5041 ppm for 6 hours/day, 5 days/week for 89 or 90 consecutive days (Cavender, 1981). This GLP study was equivalent to OECD Test Guideline 413. No mortalities were observed during the study. Clinical signs noted (including irritation, swelling, ear tag crustiness, and/or crusty eye in control and treated animals) were not related to the administration of the test article. High-dose (5041 ppm) male and female body weights were transiently depressed starting at week one, while the low-dose male and mid-dose male and female body weights were elevated as the study progressed. There were no test article related changes in ophthalmoscopy and urinalysis. The mean corpuscular hemoglobin (in high-dose males and females) and mean corpuscular haemoglobin concentration (in high-dose females only) were increased compared to controls. The increase in haemoglobin corresponded to a slight (but not significant) decreased in the number of red blood cells. The serum glutamic-pyruvic transaminase (SGPT) activity in the 2500-ppm female rats was elevated while the 5000-ppm female rats exhibited significantly decreased SGPT activity. Potassium levels in high-dose (5041 ppm) females were statistically higher than control values. In high-dose (5041 ppm) male rats, liver weights, liver/body weight ratio, liver/brain weight ratio and kidney/body weight ratios were significantly elevated. In female rats, a significant dose response was observed in increased liver weight. In high-dose (5041 ppm) female rats, the liver/body weight ratio, liver/brain ratio, and kidney/brain weight ratios were significantly elevated while the brain/body weight ratio was significantly depressed. Liver pathology showed no lesions. Significantly depressed spleen and brain weights were also observed. Only minor macroscopic lesions were observed and none were attributed to test article administration. Any neoplastic lesions observed were not related to test article administration. No changes in neurological function were observed. 

Although a NOEC was not determined by study authors, based on the data a NOAEC of 5014 ppm can be considered for subchronic inhalation toxicity given that the effects noted in both sexes at 5014 ppm were limited to non specific effects including decreased body weight and increased absolute liver weights and liver to body weight ratios.

Based on the same data SIAR concludes that the NOAEL is 5000 ppm.

Justification for classification or non-classification

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