4-methylpentan-2-ol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well documented, according to accepted guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

room temperature was 18.5 to 26 °C rather than 17 to 23 °C

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

yes

Remarks:

room temperature was 18.5 to 26 °C rather than 17 to 23 °C

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-methylpentan-2-ol

EC Number:

203-551-7

EC Name:

4-methylpentan-2-ol

Cas Number:

108-11-2

Molecular formula:

C6H14O

IUPAC Name:

4-methylpentan-2-ol

Details on test material:

- Name of test material (as cited in study report): Methyl Isobutyl Carbinol, Methyl isobutyl carbinol, 4-methyl-2-pentanol, methyl amyl alcohol.
- Physical state: Clear liquid.
- Analytical purity: 99.7%.
- Lot/batch No.: L-980710.
- Expiration date of the lot/batch: 10 July 1999.
- Stability under test conditions: Not reported.
- Storage condition of test material: Room temperature in the dark.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, England.
- Age at study initiation: Approximately 11 to 13 weeks.
- Weight at study initiation: 2.5 to 3.0 kg
- Housing: Housed individually in stainless steel cages with perforated floors in Building R14 Room 4.
- Diet (e.g. ad libitum): Standard laboratory rabbit diet (Special Diet Services STANRAB (P) SQC pellet), ad libitum. In addition, the animals were fed hay on arrival and subsequently three times a week.
- Water (e.g. ad libitum): Drinking water, ad libitum.
- Acclimation period: 12 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.5 to 26 °C.
- Humidity (%): 41 to 68%
- Air changes (per hr): Not reported.
- Photoperiod (hrs dark / hrs light): 12 / 12

The higher value for temperature recorded was 26 °C. This exceeded the 19 ± 2 °C range stated in the protocol. This deviation was not considered to have affected the integrity or validity of the study. There were no other deviations from the protocol.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL.
- Concentration (if solution): Undiluted, as supplied by the Sponsor.

Duration of treatment / exposure:

4 hours, single exposure.

Observation period:

14 days.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Dorso-Lumbar region.
- % coverage: Not reported (25 mm x 25 mm).
- Type of wrap if used: Each treatment site was covered with "Elastoplast" elastic adhesive dressing for 4 hours.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): The treatment site was washed with warm water (34 °C) to remove any residual test substance. The treated area was blotted dry with absorbent paper.
- Time after start of exposure: After 4 hours.


SCORING SYSTEM: Examination of the treated skin was made on Day 1 (i.e., approximately 60 minutes after removal of the dressing) and on Days 2, 3, and 4 (equivalent to 24, 48, and 72 hours after exposure). Additional daily observations were made to assess reversibility up to a maximum of 14 days.

Local dermal irritation was assessed using the prescribed numerical system:
Erythema and eschar formation: Grade
No erythema: 0
Very slight erythema (barely perceptible): 1
Well-defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) or eschar formation (injuries in depth) 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 (edges raised approximately 1 mm): 3
Severe oedema (raised more than 1 mm and extending beyond the area of exposure): 4

Any other lesion not covered by this scoring system was described.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 10 days

Results 2

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 12 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: 11 days

Irritant / corrosive response data:

Refer to Table 1 (Attached) for result of dermal reactions.
Well-defined erythema with slight oedema was seen in all animals. In addition, desquamation of the stratum corneum (characterised by dryness and sloughing) developed in all three rabbits accompanied by thickening of the skin in one rabbit. Dermal responses gradually ameliorated and had resolved in two animals by either Day 10 or 12. However, very slight erythema was still evident in one animal at study termination on Day 14.

Other effects:

There were not signs of toxicity or ill health in any rabbits during the observation period.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information not classified according to CLP, classified R38 according to DSD-DPD) Criteria used for interpretation of results: EU

Executive summary:

A skin irritation study on methyl iso butyl carbinol has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 404 and in compliance with GLP (Parcell, 1998).  In this study, 3 New Zealand White rabbits were exposed to 0.5 mL of undiluted methyl iso butyl carbinol on the clipped dorsal lumbar region under semi-occlusive conditions.  Animals were exposed to the test compound for 4 hours and observations were recorded at 1, 24, 48, and 72 hours after removal of the patch and residual test substance.  Additional daily observations were made up to a maximum of 14 days.  Skin reactions were scored according to a prescribed numerical system.  In all 3 animals, well-defined erythema with slight edema was observed. In addition, desquamation of the stratum corneum, characterized by dryness and sloughing of the skin, developed in all animals. In one rabbit, thickening of the skin was observed. Dermal responses were fully resolved by either Day 10 or 12 in 2 animals. However, very slight erythema was still observed in one animal at Day 14. No signs of toxicity or ill health were observed in any rabbit during the observational period. The individual mean scores over 24, 48 and 72 hours were 2.0, 2.0 and 2.0 for erythema and 2.0, 1.0 and 1.7 for edema.