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Administrative data

Description of key information

MIBK shows a low degree of toxicity by oral, dermal or inhalation routes in rats. The acute LD50 by oral route was 2080 mg/kg bw, the acute LD0 by dermal route was greater than 2000 mg/kg bw and the acute 4-hour inhalation LC50 was betweem 2000 and 4000 ppm (8200 and 16400 mg/m3, respectively).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1951
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
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, these results are deemed reliable.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Insufficient reporting of methodology and individual results
GLP compliance:
no
Remarks:
study pre-dates GLP requirements
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
No data
Doses:
Not reported
No. of animals per sex per dose:
6
Control animals:
not specified
Details on study design:
No data
Statistics:
No data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
2.08 other: g/kg body weight
95% CL:
1.91 - 2.27
Mortality:
No data
Clinical signs:
other: No data
Gross pathology:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)
Executive summary:

The rat oral LD50 was 2080 mg/kg bw when MIBK was administered as a 20% emulsion in Terginol 7 surfactant. The study used six animals per group. Additional details of the study were not included in the publication.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 080 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1951
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see remarks
Remarks:
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, these results are deemed reliable.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Insufficient reporting of methodology and results
GLP compliance:
no
Remarks:
study pre-dates GLP requirements
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No data
Route of administration:
inhalation: vapour
Type of inhalation exposure:
not specified
Vehicle:
air
Details on inhalation exposure:
No data
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
4 h
Concentrations:
2000 and 4000 ppm (8.2 and 16.4 mg/l)
No. of animals per sex per dose:
6 animals/dose level
Control animals:
not specified
Sex:
male
Dose descriptor:
LC50
Effect level:
> 8.2 - < 16.4 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Sex:
male
Dose descriptor:
LC50
Effect level:
11.6 mg/L air (nominal)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: Calculated with a standard probit model
Mortality:
At the 2000 ppm dose level, 0/6 animals died and at the 4000 ppm level all animals died.
Clinical signs:
other: No data
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
Category 4 based on GHS criteria
Executive summary:

An LC50 was not reported by the authors however, as none of the animals died at 2000 ppm and all of the animals died at 4000 ppm the LC50 is anticipated to be greater than 2000 ppm but less than 4000 ppm (8.2 and 16.4 mg/l).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating conc.
Value:
8 200 mg/m³ air

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
- body weights were 296 to 336 g for males, instead of 200 to 300 g recommended by OECD
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
1992
Deviations:
yes
Remarks:
- body weights were 296 to 336 g for males
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Crl:CD.BR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- 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.


ENVIRONMENTAL CONDITIONS
- 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.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- 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.


REMOVAL OF TEST SUBSTANCE
- 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.


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.50 mL/kg body weight.
- Concentration (if solution): Undiluted.
Duration of exposure:
24 hours.
Doses:
2000 mg/kg body weight.
No. of animals per sex per dose:
5 animals per sex.
Control animals:
no
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
Statistics:
Not reported; however, not required for acute toxicity study.
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.
Sex:
male/female
Dose descriptor:
LD0
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.
Mortality:
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.
Interpretation of results:
GHS criteria not met
Conclusions:
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw

Additional information

Acute Toxicity: Oral

The potential acute oral toxicity of methyl i-butyl ketone was assessed in rats by Smyth et al. (1951). 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.(1951) determined the LD50 of methyl i-butyl ketone in rats to be 2080 mg/kg body weight as assessed following oral gavage administration of a range of methyl i-butyl ketone concentrations (reported as 10, 1, 0.1 ,etc. g/kg body weight).

Acute Toxiciy: Dermal

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 14th day. 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.

Acute Toxicity: Inhalation

The potential acute inhalation toxicity of methy i-butyl ketone was assessed in rats by Smyth et al (1951), and as discussed above, this study is lacking in methodological details, but is deemed reliable. Six rats per dose level were exposed to 2000 or 4000 ppm (8.2 or 16.4 mg/l) of vapors of the test substance for 4 hours. At the 4000 ppm dose level, all the animals died, and at the 2000 ppm dose level, no animals died.


Justification for selection of acute toxicity – oral endpoint
Key study

Justification for selection of acute toxicity – inhalation endpoint
Key study

Justification for selection of acute toxicity – dermal endpoint
Key study

Justification for classification or non-classification

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

According to CLP criteria, this substance warrants a classification Toxicity Category IV: harmful if inhaled, as set out in Regulation (EC) NO. 1272/2008.