Menthol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: well documented and scientifically acceptable

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

The day before the experiment was started the rabbits were weighed and an area of 10 x 10 cm on the back was clipped as closely as possible with an electric clipper.
On the experimental day the rabbits were physically restrained on a test table, and the backs were treated on six different fields: Two anterior treatment sites, two centrally located test sites and two posterior treatment sites. To each of the fields about 0.5 ml of one of the test concentrations was applied and covered with gauze packs, 2.5 x 2.5 cm. The gauze packs were secured with a cross of 1 cm wide adhesive tape and fixed with Scanpor tape, 7.5 cm width, loosely wound round the trunk. Five test concentrations were used: 100%, 50%, 25%, 5%, or 1%.
After an exposure time of 4 hours the tape and packs were removed and the related skin was cleaned with soap and lukewarm water. The skin reactions were read.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Menthol

EC Number:

201-939-0

EC Name:

Menthol

Cas Number:

89-78-1

Molecular formula:

C10H20O

IUPAC Name:

2-isopropyl-5-methylcyclohexanol

Specific details on test material used for the study:

OTHER SPECIFICS: Name of the test substance as cited in the report: Menthol rac.

Test animals

Species:

rabbit

Strain:

Himalayan

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

other: diethylphthalate (DEP)

Controls:

not required

Duration of treatment / exposure:

4 hours

Observation period:

4.5, 24, 48, and 72 hours, 7, and 14 days

Number of animals:

4 female rabbits

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: undiluted material

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: undiluted material

Any other information on results incl. tables

On day 7, all sites treated with a 100% concentartion wer covered with a massive layer of white-brown

seales on three test animals and the test site ofone test animal was covered with a thin

layer of white scales. Sites treated with a 50% concentration showed white scales on all rabbits. The test

sites, treated with a 25% concentration showed scattered white scales on one rabbit.

On day 14, the sites treated with a 100% concentration was still covered with white to white-brown

scales, but the underlying skin was intact. The sites treated with a 50% concentration showed scattered

seale formation on intact skin on 3 of the test animals.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Executive summary:

The day before the experiment was started the rabbits were weighed and an area of 10 x 10 cm on the back was clipped as closely as possible with an electric clipper.

On the experimental day the rabbits were physically restrained on a test table, and the backs were treated on six different fields: Two anterior treatment sites, two centrally located test sites and two posterior treatment sites. To each of the fields about 0.5 ml of one of the test concentrations was applied and covered with gauze packs, 2.5 x 2.5 cm. The gauze packs were secured with a cross of 1 cm wide adhesive tape and fixed with Scanpor tape, 7.5 cm width, loosely wound round the trunk. Five test concentrations were used: 100%, 50%, 25%, 5%, or 1%.

After an exposure time of 4 hours the tape and packs were remoced and the treated skin was cleaned with soap and lukewarm water. The skin reactions were read.

With the undiluted test substance menthol was irritating to the skin (erythema sore: 3 and and edema score: 3). The undiluted compounds were irritating to the skin. Dilution of the compounds led to a pronounced decrease in the irritating properties of the

compounds. No skin reaction at all were observed for D-menthol and menthol liquid at 5 % dilution and for L- and D/L-menthol at 1 % dilution.