3-methylbutanone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24-hour exposure followed by a 14-day observation period

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted according to a method similar to OECD Guideline 402 and reviewed by Quality Assurance. Conduct of study according to all aspects of GLP was not confirmed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

not specified

Principles of method if other than guideline:

Method is an in vivo study using 5 rats/sex. A single limit dose of 20 mL/kg bw of the test substance was held in contact with the clipped dorsum of the animals under an occlusive cuff for 24 hours. Animals were observed after exposure for mortality, dermal reactions, and weight changes for a total of 14 days. Gross pathology was performed at study termination.

GLP compliance:

not specified

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-2-butanone

IUPAC Name:

3-methyl-2-butanone

Constituent 2

Reference substance name:

3-methylbutanone

EC Number:

209-264-3

EC Name:

3-methylbutanone

Cas Number:

563-80-4

Molecular formula:

C5H10O

IUPAC Name:

3-methylbutan-2-one

Constituent 3

Reference substance name:

methylbutanone; methyl isopropyl ketone; MIPK

IUPAC Name:

methylbutanone; methyl isopropyl ketone; MIPK

Details on test material:

-Test substance: Methyl isopropyl ketone
-Date of manufacture: October 1987
-Source: Tennessee Eastman Company
-Specific gravity: 0.805

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Test animals:
-Strain: Crl:CD®(SD)BR
-Sex: Male and Female (5 of each sex/group)
-Body weight (at study initiation): Males (221-247 g), Females (172-204 g)

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Following depilation of each animal's dorsum, a single dose of 20.0 mL/kg bw of the test substance was applied under an occlusive cuff and wrap. After a 24 hour exposure period, the cuffs and wrappings were removed.

Duration of exposure:

24 hours

Doses:

20 mL/kg bw

No. of animals per sex per dose:

5 rats/sex

Control animals:

no

Details on study design:

Method is an in vivo study using 5 rats/sex. A single dose of 20 mL/kg bw of the test substance was held in contact with the dorsum of the animals under an occlusive cuff for 24 hours. Animals were observed after exposure for mortality, dermal reactions, and weight changes for a total of 14 days. Gross pathology was performed at study termination. Based on a specific gravity of 0.805, the limit dose of test substance administered in this study was approximately 16 g/kg bw. This dose was significantly higher than the 2000 mg/kg bw limit dose described in OECD Guideline 402.

Statistics:

no data

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 20 mL/kg bw

Mortality:

One female died 3.67 hours after initial application of the test substance. All other animals survived the 14-day observation period.

Clinical signs:

other: Two to five hours after initial application of the test substance, moderate weakness was noted in all animals, implying percutaneous absorption of the test substance. No other clinical observations were noted.

Gross pathology:

In the female that died during the exposure period, moderate necrosis of the skin of the back and red discoloration of the inguinal hair were noted. The cause of death was not determined.

No treatment-related changes were observed at necropsy in animals which survived the 14-day observation period. Other lesions were not considered treatment-related, and no tissue was collected for microscopic evaluation.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

Methyl isopropyl ketone was not acutely toxic by the dermal route in rats under conditions used in this study. A single female died within four hours of test substance application. No cause of death was determined. All other animals survived and gained weight normally. Moderate weakness, a sign of central nervous system depression, was observed in all animals within 2-5 hours of test substance application. No treatment-related changes were observed at necropsy in animals that survived to study termination. The dermal LD50 in rats was > 20.0 mL/kg bw (equivalent to > 16 g/kg bw).

Based on an acute dermal LD50 value of > 20.0 mL/kg bw in male and female rats, methyl isopropyl ketone is not classified for Acute Toxicity by the dermal route under the UN GHS regulations or the EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008. Based on clinical signs indicating reversible effects on the central nervous system, methyl isopropyl ketone is classified as Category 3 for classification and labeling under GHS for Specific Target Organ Toxicity – Single Exposure.

Executive summary:

In an acute dermal toxicity study, 5 rats/sex were exposed to 20 mL/kg bw of methyl isopropyl ketone under occlusive contact for 24 hours. Under the conditions of this study, one death occurred and the dermal LD50 was considered to be > 20.0 mL/kg bw. Signs of irritation in the female that died during exposure were limited to moderate necrosis at the application sites.  A body weight gain was noted for all surviving animals over the 2-week observation period. Based on the results of this study, methyl isopropyl ketone is not expected to be acutely toxic upon skin contact under conditions of normal use; however, methyl isopropyl ketone may be absorbed through the skin and dermal exposure to large volumes for prolonged periods of time may cause central nervous system effects.