4-methylpentan-2-one

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

-

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1989-05-16, 1989-06-09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Not GLP, but according to most recent guidelines (OECD 406). No deviations.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1981

Deviations:

no

Remarks:

Most recent OECD guidelines followed during time of study.

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1981

Deviations:

no

Remarks:

Most recent OECD guidelines followed during time of study

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Most recent OECD guidelines followed during time of study.

Test material

Test material information

Constituent 1

Reference substance name:

4-methylpentan-2-one

EC Number:

203-550-1

EC Name:

4-methylpentan-2-one

Cas Number:

108-10-1

Molecular formula:

C6H12O

IUPAC Name:

4-methylpentan-2-one

Details on test material:

- Name of test material (as cited in study report): Methylisobutylketon (methyl isobutyl ketone, 4-methyl- 2- pentanon)
- Substance type: organic
- Physical state: liquid, clear
- Analytical purity: 99.7 %
- Other: density (20 °C): 0.8 g/cm3; pH: neutral; vapor pressure (20 °C): 21.5 hPa; boiling point (1013 hPa): 114-117 °C; flash point: 14 °C.

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: albino Bor: DHPW

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen Germany
- Weight at study initiation: test group : 384 g; control group (average): 391 g
- Housing:1-5 animals in Makrolon cages type IV
- Diet: ad libitum, G4 Allendiät für Meerschweinchen, Ssniff Spezialfutter GmbH
- Water: ad libitum, tap water
- Acclimation period: 5-8 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1
- Humidity (%): 60 ± 5
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

corn oil

Induction 2

Concentration / amount:

0.1 cm3 of 5 % test substance (TS) in vehicle (1st induction); 2X4 cm filter paper with 100 % TS (2nd induction); 2X2 cm filter paper with 30 % TS in vehicle (challenge)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

corn oil

Challenge 2

Concentration / amount:

0.1 cm3 of 5 % test substance (TS) in vehicle (1st induction); 2X4 cm filter paper with 100 % TS (2nd induction); 2X2 cm filter paper with 30 % TS in vehicle (challenge)

No. of animals per dose:

20 (test) and 10 (control)

Details on study design:

RANGE FINDING TESTS: 100 % TS is irritant for the skin

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal then epicutaneous)
- Exposure period: 48 h (epicutaneous)
- Test groups: 1st induction: Freund's complete adjuvant (FCA) + H2O (1:1); TS; TS + FCA (1:1). 2nd induction: TS
- Control group: 1st induction: FCA + H2O (1:1); vehicle; FCA + vehicle (1:1). 2nd induction: vehicle
- Site: back (R and L shoulder)
- Frequency of applications: weekly
- Duration: 0-7 d
- Concentrations: same throughout

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (epicutaneous)
- Day(s) of challenge: 21
- Exposure period: 24 h
- Test groups: TS (L side); vehicle (R side)
- Control group: TS (L side); vehicle (R side)
- Site: flank (R and L)
- Concentrations: 30 % TS
- Evaluation (hr after challenge): 24 and 48 h

Challenge controls:

The control group served also as naive control (tested with 30 % TS during challenge)

Positive control substance(s):

no

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Remarks on result:

not measured/tested

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

positive control

Remarks on result:

not measured/tested

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

30 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none reported

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none reported.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

30 %

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

none reported

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none reported.

Results 5

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none reported

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: challenge control. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none reported.

Results 6

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none reported

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: challenge control. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none reported.

Any other information on results incl. tables

For all animals in both groups were observed local reactions (reddening and swelling) following the respective substances application. Weight gain remained normal in all animals of both groups throughout the study and did not show to be affected by the treatment.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

Methyl isobutyl ketone in the guinea pig Maximation test of Magnusson and Klingman produced no sensitizing reaction.

Executive summary:

The skin sensitization potential of methyl iso butyl ketone was assessed in a study performed according to OECD Guidelines for the Testing of Chemicals No. 406 in female albino Bor: DHPW guinea pigs (Mürmann, 1989).  In this study, 20 animals comprised the methyl iso butyl ketone test group and 10 animals comprised the vehicle control group.  The intradermal induction was carried out with 0.1 ml of 5% methyl iso butyl ketone in vehicle (corn oil), and epicutaneous induction was performed with undiluted methyl iso butyl ketone to the shoulder area.  The challenge exposure was conducted with 30% methyl iso butyl ketone under occlusive conditions.  Skin reactions were observed and recorded 24 and 48 hours after the challenge exposure.  Test and control animals displayed normal body weight gain throughout the investigation. Local reactions (reddening and swelling) were observed in all treated animals. Some irritation reactions were also observed in the control animals. Also, the skin of the animal may have been abraded; however, there is insufficient details to determine if the whole test area was abraded or only partially. Therefore, the results of skin irritation were deemed unreliable. Under the experimental conditions, methyl iso butyl ketone produced no sensitizing reaction.