3-methylbutanone

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study conducted according to acceptable scientific standards and reviewed by Quality Assurance, although conduct of study according to all aspects of GLP could not be confirmed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

no

Principles of method if other than guideline:

Groups of male Hartley guinea pigs were used to determine the dermal sensitization potential of the test substance using the Kodak Footpad Method. Initially, the irritant potential of a 1% solution of the substance in a 7:2:1 mixture of acetone, dioxane, and guinea pig fat was determined following application to the clipped back skin of several animals. The results of the preliminary irritation study were used to determine the concentration of the test substance to be used in the sensitization study. In the sensitization study proper, groups of ten animals were induced by injection of 0.05 mL of either a 1% solution of the substance in Freund's Complete Adjuvant, or 0.05 mL of Freund's Complete Adjuvant alone. The injections were made into one footpad for each animal. Seven days later, both groups of animals were challenged topically with 0.5 mL of a 10% solution of the test substance in the mixture of acetone, dioxane, and guinea pig fat described above. After 48 hours, the responses in animals induced with 1% compound in Freund's were compared to the responses in animals induced with Freund's only. The numbers of animals demonstrating a response in each group were recorded, and responses were noted as slight, moderate, or strong. The negative control animals, i.e., those induced with Freund's alone, were used to quantify responses associated with Freund's only. The number of animals responding to challenge and the degree of positive response were used to determine the sensitization potential of the test substance.

GLP compliance:

not specified

Type of study:

other: Kodak Footpad Method. The Kodak Footpad method was listed as an alternate method for evaluating dermal sensitization in the first edition of the OECD Guideline for evaluating dermal sensitization.

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

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male

Details on test animals and environmental conditions:

-Strain: Crl(HA)BR Hartley
-Body weight (Irritation phase): 403-538 g
-Initial body weight (Induction and Challenge Phase): 300-343 g

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal

Vehicle:

other: Irritation and challenge phases: 7:2:1 acetone:dioxane:guinea pig fat; Induction phase: Freund's Complete Adjuvant

Induction 2

Concentration / amount:

Preliminary Irritation Phase: 1.0% in acetone + dioxane + guinea pig fat.
Induction Phase: 1.0% in Freund's Complete Adjuvant
Challenge Phase: 10.0% in acetone + dioxane + guinea pig fat.

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other: Irritation and challenge phases: 7:2:1 acetone:dioxane:guinea pig fat; Induction phase: Freund's Complete Adjuvant

Challenge 2

Concentration / amount:

Preliminary Irritation Phase: 1.0% in acetone + dioxane + guinea pig fat.
Induction Phase: 1.0% in Freund's Complete Adjuvant
Challenge Phase: 10.0% in acetone + dioxane + guinea pig fat.

No. of animals per dose:

10

Details on study design:

Groups of male Hartley guinea pigs were used to determine the dermal sensitization potential of the test substance using the Kodak Footpad Method. Initially, the irritant potential of a 1% solution of the substance in a 7:2:1 mixture of acetone, dioxane, and guinea pig fat was determined following application to the clipped back skin of several animals. These animals were not used in the study proper, but were used only to estimate the irritant potential of the test substance, and to help in the determination of the concentration of test substance to be used in the sensitization study. In the subsequent sensitization study, groups of ten animals were induced by injection of 0.05 mL of either a 1% solution of the substance in Freund's Complete Adjuvant, or 0.05 mL of Freund's alone. Injections were made into the animal's footpad. Seven days later, the backs of the animals were clipped and both groups of animals were challenged topically with 0.5 mL of a 10% solution of the test substance in the mixture of acetone, dioxane, and guinea pig fat described above. Animals were depilated after 24 hours to assist in the determination of dermal responses. After both 24 and 48 hours, the responses in animals induced with 1% compound in Freund's were compared to the responses in animals induced with Freund's only. The numbers of animals demonstrating a response in each group were recorded, and responses were noted as slight, moderate, or strong. The negative control animals, i.e., those induced with Freund's alone, were used to quantify responses associated with the irritant potential of Freund's only. The number of animals responding to challenge and the degree of positive response were used to determine the sensitization potential of the test substance.

Challenge controls:

10 male Hartley guinea pigs induced with Friend's Complete Adjuvant only.

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No reactions were observed at challenge in animals previously induced with the test substance in Freund's Complete Adjuvant.

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No reactions were observed at challenge in animals previously induced with the test substance in Freund's Complete Adjuvant..

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

10%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

No reactions were observed at challenge in animals previously induced with the test substance in Freund's Complete Adjuvant.

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 10%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No reactions were observed at challenge in animals previously induced with the test substance in Freund's Complete Adjuvant..

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Both the test group and the control group treated with Freund’s Complete Adjuvant alone had similar responses when tested using the Kodak Footpad Method. Under conditions used in this study, methyl isopropyl ketone was not a dermal sensitizer.

Based on an absence of a positive sensitization reaction in this study, methyl isopropyl ketone is not classified for Skin Sensitization according to GHS.

Executive summary:

In a dermal sensitization study using the Kodak Footpad Method, groups of ten male Hartley guinea pigs were induced by injection in the footpad with either 0.5 mL of a 1.0% solution of methyl isopropyl ketone in Freund's Complete Adjuvant or 0.5 mL of Freund's alone. One week later, the animals were challenged with a 10% solution of methyl isopropyl ketone in acetone: dioxane: guinea pig fat (7:2:1). The 10.0% solution was used since a 1% solution of the test substance in the same solvent was found to be non-irritating in the preliminary irritation study. Twenty-four and forty-eight hours after challenge, all animals in the control and test groups appeared normal, and no positive dermal reactions were observed. Based on the results of this study using the Kodak Footpad Method, it was determined that methyl isopropyl ketone was not a dermal sensitizer.