4-methylpentan-2-one

Endpoint summary

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:

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 '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 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

Route of administration:

inhalation: vapour

Type of inhalation exposure:

not specified

Vehicle:

other: no data

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:

> 2 000 - < 4 000 ppm

Based on:

test mat.

Exp. duration:

4 h

Sex:

male

Dose descriptor:

LC50

Effect level:

11.6 mg/L air

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:

Toxicity Category IV

Remarks:

Harmful if inhaled CLP (EC 1272/2008)

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:

other: Well documented, according to accepted guidelines

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:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: CLP (EC 1272/2008)

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 5^th to 14^thday. 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 5^th to 14^th 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 vapor 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.