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Administrative data

Description of key information

In 120-day repeated dose toxicity studies diethyl ketone was administered in drinking water at a concentration of 2.4 % (corr. to 1860 mg/kg bw/d) to rats. This dose represents a LOEL, because reduced body weight gain and increased kidney weights seen. In a 90-day repeated inhalation toxicity study rats were exposed to 0, 1250, 2500 or 5000 ppm methyl ethyl ketone.  The only effects observed were changes in organ weight and urine volume at 5000 ppm. Due to the absence of corrobarative findings, these effects were assessed as non-adverse and a NOAEC of 5000 ppm was derived.

Key value for chemical safety assessment

Additional information

Oral administration

In a subchronic toxicity study diethyl ketone was administered to five female Wistar rats in drinking water for 120 days at a concentration of 2.4 % which corresponds to 1860 mg/kg bw/d (EPA/OTS, 1983). Parameters examined in this study included neurobehaviour, diet and water consumption, body weight gain, absolute and relative liver and kidney weights as well as gross pathology. No neurologic alterations were noted during the study and no significant gross lesions were seen after necropsy. Body weight gain was statistically significantly decreased, whereas absolute kidney weight and kidney weight relative to body weight were statistically significantly increased.

A subsequent subchronic toxicity study using an identical study design (administration of 2.4% diethyl ketone in drinking water (1860 mg/kg bw/d ) to five female Wistar rats for 120 days) focused on histopathological examination of organs and neurological tissues (EPS/OTS, 1983). The organs examined fulfil the requirements of OECD test guideline 408. No neuropathological effects were noted. The histopathological changes observed in medastinal lymph nodes (hemorrhage and hemosederosis), cecum (nematodiasis), spleen (hemosiderosis) and thymus (hemorrhage) were not considered to be treatment related as they were also seen in the control group at comparable incidence and severity. The gastric gland dilatation noted in the stomach of 2/5 test group animals but not in control group animals represented spontaneous histologic alterations commonly seen in this stock of rats.

In the absence of a histopathological correlate in the second study, the increased kidney weight observed in the first study is considered as a non-adverse finding. The relevance of the satistically significantly reduced body weight gain in the first study remains unclear, because no information on absolute body weight was given in this study and no body weight data were reported in the publication of the second study. Thus, based on the results obtained in both studies the dose level of 1860 mg/kg bw/d represents a LOEL.


Inhalation exposure

There are no studies available for diethyl ketone. However, the experimental data presented below on the structural analogue methyl ethyl ketone can be used in a read-across approach. A justification of the use of data on methyl ethyl ketone for read-across is given in section 13 of the IUCLID file.

In a subchronic inhalation toxicity study (Cavender et al., 1983) with the structural analogue methyl ethyl ketone (MEK) groups of 15 male and 15 female Fisher 344 rats were exposed to 0, 1250, 2500 or 5000 ppm MEK vapors 6 hours a day, 5 days a week for a duration of 90 consecutive days. 5 male and 5 female rats per dose group were designated for special neuropathological examinations. Transient, statistically significant depressions of mean body weight gains were observed in male and female rats exposed to the highest concentration of methyl ethyl ketone. No effects were found in the amount of food consumed, tests for neurological function, ophthalmologic observations or hematologic or serum chemistry parameters which were attributed to test article administration. At necropsy, slight but statisitically significant increases in absolute liver weight were noted in 1200 ppm and 2500 ppm females. Increases in liver weight, liver weight/body weight ratios and liver weight/brain weight ratios were observed in both 5000 ppm male and 5000 ppm female rats. In the former kidney weight/body weight ratios also were elevated. Spleen and brain weight, and brain weight/body weight ratios were depressed while kidney weight/brain weight ratios were elevated in 5000 ppm female rats. Urine volumes in 5000 ppm male rats were higher than control values. All of the findings at 5000 ppm were statistically significant, but of uncertain biological significance. Neuropathological and routine histopathological studies including examination of reproductive organs did not reveal any lesions that could be attributed to MEK exposure. Due to the lack of any other corroborative findings, the effects on some organ weights and urine volume in males seen at 5000 ppm are considered as non-adverse effects. Also the decreased body weight gain at 5000 ppm represents a non-adverse effect, as it was transient. Thus, a NOAEC of 5000 ppm (corresponding to 14.7 g/m³) is derived. 

Justification for classification or non-classification

Based on the results of the 120-day oral dose toxicity studies for diethyl ketone and the result of the 90 -day inhalation toxicity study with the structural analogue methyl ethyl ketone, it is concluded that diethyl ketone is not subject to classification and labelling according to Directive 67/548/EEC and Regulation 1272/2008/EC.