4-methyl-4-phenylpentan-2-ol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with standard test guidelines (OECD TG404) and is GLP compliant.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4-methyl-4-phenylpentan-2-ol

EC Number:

218-002-7

EC Name:

4-methyl-4-phenylpentan-2-ol

Cas Number:

2035-93-0

Molecular formula:

C12H18O

IUPAC Name:

4-methyl-4-phenylpentan-2-ol

Test material form:

other: clear liquid

Details on test material:

- Name of test material: 4-Methyl-4-phenyl-pentan-2-ol
- CAS number: 2035-03-0

Test animals

Species:

rabbit

Strain:

other: Chbb:HM SPF albino

Details on test animals or test system and environmental conditions:

Animal room with filtered air at a temperature of 20°C ± 3°C, relative humidity between 30 % and 70 % and air changes 10 times/ hour. The room was illuminated to give a cycle of 12 hours Iight and 12 hours darkness. Light was on from 6 am to 6 pm.
During a pre-period of at least one week and throughout the experiment the rabbits were caged individually in PPO cages (floor area: 2576 sq. cm) with perforated floor.

A pelleted complete rabbit diet "Altromin 2123" from Altromin, D-32791 Lage, Lippe, was available ad libitum. Analyses for major nutritive
components and relevant possible contaminants are performed regularly on the diet. Certificates of analysis are retained.

Drinking water ad libitum.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Initial test:
0.5mL was applied to a 16-layer gauze patch (2.5 x 2.5 cm), the patch was placed on the appropriate anterior test field and secured semi-occlusively with adhesive Gothaplast tape (2.5 cm). After an exposure time of 3 min. the first patch was removed, the test field was marked and the treated skin was cleaned with mild soap and lukewarm water.

As no reaction was observed a second patch with 0.5 mL test item was applied on the median test field of the rabbit back. In order to improve the security of the patch, the trunk of the animal was additionally wound with 5 cm wide adhesive Gothaplast tape. After an exposure time of 1h. the second patch was removed, the test field was marked and the treated skin was cleaned with mild soap and lukewarm water. The skin reaction was first assessed immediately after the termination of exposure. Also after 1 h. no corrosive effects were observed so that the exposure time could be extended to 4 h.

An amount of 0.5 mL of the test item was applied on a third patch and put on the posterior test field of the animal. Adhesive Gothaplast tape (2.5 cm and 5 cm wide) served again as the semi-occlusive securing. After a 4-hour exposure time the third patch was removed, the test field was marked and the treated skin was cleaned with mild soap and lukewarm water. The first assessment of the skin reaction took place again immediately after the termination of exposure.

Confirmatory test:
Likewise for the confirmatory test the animals were physically restrained on a test table and the back of each rabbit was divided in four test Fields. Always the anterior right field was selected as the test area for the test item. An amount of 0.5 ml of the test item was applied on a 16-layer gauze patch (2.5 cm x 2.5 cm) and the patch was placed on the appropriate test field. The gauze patch was secured semi-occlusively with adhesive Gothaplast tape (2.5 cm wide) and fixed with Gothaplast tape (5 cm wide) loosely wound round the trunk of the animals. After an exposure time of 4 h. the tape and patch were removed, the test field was marked and the treated skin was cleaned with mild soap and lukewarm water.

Duration of treatment / exposure:

Initial test 3 minutes - 1st patch ; 4hours for 2nd and 3rd patches ;

Confirmatory test - 4hours

Observation period:

Immediately after removal of each patch and 1h, 24h, 48h and 72h after termination of exposure

Number of animals:

3

Details on study design:

The skin irritant effect of 4-methyl-4-phenylpentan-2-ol was investigated according to the method recommended in the OECD Guideline No. 404, "Acute Dermal Irritation/ Corrosion", 2002, the commission directive 2004/73/EC "B.4. Acute Toxicity: Dermal Irritation/Corrosion", 2004, and OECD document "Harmonised Integrated Classification System for Human Health and Environmental Hazards of Chemical Substances and Mixtures", 2001.

During an initial test using one female albino rabbit a sequential application (exposure time 3 min., 1 h. and 4 h.) of4-methyl-4-phenylpentan-2-ol
was carried out on one site of the left back area each time. The skin was examined for signs of irritation immediately after application and 1h., 24h., 48h. and 72h after the termination of exposure on day 1 as well as on days 7, 14 and 21. Since the animal did show well-defined signs of skin irritation but no full thickness destruction of the skin within the observation period of 21 days it was decided to carry out a confirmatory test with two additional animals in order to allow a categorization of the test item based on the classification criteria.

Two female albino rabbits were exposed to the test item at one skin site on the back during the confirmatory test. After a 4-hour exposure time the test item was removed and the skin was examined 1 h., 24 h., 48 h. and 72 h. after the termination of exposure on day 1 as well as on days 7 and 14.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 21days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 14 days

Results 6

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean of scores at 24, 48 and 72 hours

Score:

0

Max. score:

0

Reversibility:

fully reversible within: 14 days

Any other information on results incl. tables

Animal  wt kg  exposure time  test field  erythema            oedema                    0h  1h  24h 48h  72h  mean of 24, 48 and 72 hour scores  0h  1h 24h   48h  72    mean of 24, 48 and 72 hour scores  3137  2.6  4h  posterior le  2 1  2  2  2   2.0  0 0  1  1  1  1.0   3119  2.5  4h  anterior ri    1  1  1  1 1.0    0  0 0  0 0.0  3120  2.5  4h  anterior ri    1 2  2  2  2.0    0  0  0  0  0.0

Applicant's summary and conclusion

Interpretation of results:

slightly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to regulation (EC) No 1272/2008, 4-methyl-4-phenylpentan-2-ol is not classified as a skin irritant. All mean values for erythema and oedema were < 2.3 and effects were fully reversible within 14 days in 2 of 3 animals.

Executive summary:

During an initial test using one female albino rabbit a sequential application (exposure time 3 min., 1 h. and 4 h.) demonstrated well defined signs of skin irritation, but no full thickness destruction of the skin, within the observation period of 21 days. A confirmatory test was carried out with two additional animals in order to allow a categorization of the test item based on the classification criteria. Consequently, two female albino rabbits were exposed to the test item at one skin site on the back during this confirmatory test. After a 4-hour exposure time the test item was removed and the skin was examined 1 h., 24 h., 48 h. and 72 h. after the termination of exposure on day 1 as well as on days 7 and 14. Skin reactions ranging from slight to well-defined were also observed in these two additional animals. All effects were fully reversible within 21 days. Under the experimental conditions described in this report the mean scores after the 4-hour exposure were:

Animal No.       Erythema       Oedema

3137                     2.00              1.00

3119                     1.00              0.00

3120                     2.00              0.00

Under the experimental conditions the mean score for erythema was 1.7 and for oedema 0.3.

According to the criteria of the regulation (EC) No 1272/2008, 4 -methyl-4-phenylpentan-2-ol is not classified as a skin irritant - all mean values for erythema and oedema were < 2.3 and effects were fully reversible within 14 days in 2 of 3 animals. According to UN GHS, classification as mild irritantion Cat 3 is needed.