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Toxicological information

Acute Toxicity: dermal

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Administrative data

acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented, according to accepted guidelines

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
- body weights were 296 to 336 g for males, instead of 200 to 300 g recommended by OECD
according to guideline
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
- body weights were 296 to 336 g for males
GLP compliance:
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Details on test material:
- Name of test material (as cited in study report): Methyl iso butyl ketone.
- Physical state: Colourless liquid.
- Analytical purity: 99.5%.
- Lot/batch No.: D215600281.
- Stability under test conditions: Not reported.
- Storage condition of test material: Stored at room temperature.

Test animals

other: Crl:CD.BR
Details on test animals or test system and environmental conditions:
- Source: Charles River (UK) Ltd., Margate.
- Age at study initiation: 7 to 9 weeks (males); 10 to 11 weeks (females).
- Weight at study initiation: 296 to 336 g (males); 238 to 268 g (females).
- Fasting period before study: Not reported.
- Housing: Individually accommodated in suspended steel mesh cages.
- Diet (e.g. ad libitum): SQC(E) Rat and Mouse Maintenance Diet No. 1, from Special Diets Services Ltd., Witham), ad libitum.
- Water (e.g. ad libitum): Mains water was provided, ad libitum.
- Acclimation period: 15 days.

- Temperature (°C): 19 to 25 °C.
- Humidity (%): 40 to 70%
- Air changes (per hr): 15 per hr.
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light.

Administration / exposure

Type of coverage:
unchanged (no vehicle)
Details on dermal exposure:
- Area of exposure: Dorsum of the rat.
- % coverage: 10% of the total body surface.
- Type of wrap if used: The patch was retained in place by an elasticated, open-weave, adhesive bandage "Steroban" from Steroplast Ltd., Bredbury, wrapped securely around the torso of the animals.

- Washing (if done): No. The test site was lightly brushed clean of any solid residues and swabbed with moist cotton wool at removal of test substance.
- Time after start of exposure: The bandage and patch were removed 24 h after application.

- Amount(s) applied (volume or weight with unit): 2.50 mL/kg body weight.
- Concentration (if solution): Undiluted.
Duration of exposure:
24 hours.
2000 mg/kg body weight.
No. of animals per sex per dose:
5 animals per sex.
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days.
- Frequency of observations and weighing: Dermal reactions were recorded following removal of the dressing on Day 2 and twice daily on Days 2, 3, and 4 and once daily from the fifth to last day of the observation period. Rats were weighed on day before dosing, Days 1, 8, and 15.
- Necropsy of survivors performed: Yes.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Clinical signs were recorded frequently on Day 1 and regularly for the remainder of the study (the minimum schedule being at least once within half an hour of dosing, four times within four hours of dosing, twice daily on Days 2, 3, and 4 and once daily from the fifth to last day of the observation period).

Erythema and oedema were scored as follows:

Erythema & eschar: Grade
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate erythema: 3
Severe erythema (beet redness) or eschar formation preventing grading of erythema: 4

Oedema: Grade
No oedema: 0
Very slight oedema (barely perceptible): 1
Slight oedema (edges of are well-defined by definite raising: 2
Moderate oedema: 3
Severe oedema (raised more than 1 mm and extending beyond the dermal test site): 4
Not reported; however, not required for acute toxicity study.

Results and discussion

Preliminary study:
A preliminary investigation was conducted using two female rats dosed at 2000 mg/kg body weight. Based on the results of this investigation, the limit dose level was selected for the main study.
Effect levels
Dose descriptor:
Effect level:
>= 2 000 mg/kg bw
Remarks on result:
other: No irritation reactions or other dermal changes at the sites of application of the test article.
No animal died following a single dermal application of methyl iso butyl ketone to rats at 2000 mg/kg body weight.
Clinical signs:
other: No clinical signs of systemic reaction to treatment were noted during 14-day observation period. Sores were noted on the dorsum of two animals; however, these were remote from the dose site and not considered to be treatment related. The most likely cau
Gross pathology:
No macroscopic changes were apparent during necropsy of the animals killed on Day 15.
Other findings:
Not applicable.

Applicant's summary and conclusion

Interpretation of results:
not classified
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
A single (24-hour) semi-occluded topical application of methyl iso butyl ketone to rats at a dose level of 2000 mg/kg body weight caused no death. No clinical signs of systemic toxicity or dermal reactions to application of the test article were apparent during the observation period. The acute median lethal dermal dose (LD0) and acute dermal minimum lethal dose of methyl iso butyl ketone were found to exceed 2000 mg/kg body weight.
Executive summary:

The potential acute dermal toxicity study of methyl i-butyl ketone was assessed in Crl:CD. BR rats in accordance with OECD Guidelines for the Testing of Chemicals No. 402 and in compliance with Good Laboratory Practice (Gardner, 1996). In a limit test, 5 male and 5 female rats were treated with 2000 mg/kg body weight of undiluted test article with a semiocclusive covering for 24 hours. Dermal reactions were recorded following removal of the dressing on day 2 and twice daily on days 2, 3, and 4, and once daily from the 5th to 14thday. Rats were weighed before dosing and on days 1, 8, and 15. Necropsy was performed and organ weights were recorded and histopathology was performed. No animals died during the test or observation period and no clinical signs of toxicity were noted. Additionally, there were no irritation reactions or other dermal changes at the sites of application of the test article. All animals achieved body weight gains during the first and second weeks of the study and there were no macroscopic changes observed at necropsy. The acute median lethal dose was determined to be greater than 2000 mg/kg body weight.