4-methyl-4-phenylpentan-2-ol

Endpoint summary

Description of key information

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, . Under the experimental conditions the mean score for erythema was 1.7 and for oedema 0.3. According to the criteria of regulation (EC) No 1272/2008, 4 -methyl-4 -phenylpentan-2 -ol is not classified as a "Skin Irritant" as all mean values for erythema and oedema were < 2.3 and effects were fully reversible within 14 days in 2 of 3 animals.
The local effect of 4-methyl-4 -phentylpentan-2 -ol on eyes was investigated according to the method recommended in the OECD Guideline No. 405, "Acute Eye Irritation/ Corrosion", April 2002, the commission directive 2004/73/EC "B.5. Acute Toxicity: Eye Irritation/ Corrosion", April 2004, and the OECD document „Harmonised Integrated Classification System for Human Health and Environmental Hazards of Chemical Substances and Mixtures" August 2001. Corneal opacity scores were greater or equal to 1 (mean values of 1, 1.33 and 2). Classification as Eye irritant Cat 2 is warranted.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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.

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.

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

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

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

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

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

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

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye 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 TG 405) and is GLP compliant.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

other: Chbb:HM(SPF)

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River, Deutschland GmbH or DIMED Schonwalde GmbH Schonwalde
- Age at study initiation: not stated
- Weight at study initiation: not stated
- Housing: The study took place in animal room with filtered air
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: During a pre-period of at least one week and throughout the study the rabbits were caged individually in PPO cages (floor area: 2576 sq.cm) with perforated floor.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%):relative humidity between 30 % and 70 %
- Air changes (10 per hour)
- Photoperiod (hrs dark / hrs light):The room was illuminated to give a cycle of 12 hours light and 12 hours darkness. Light was on from 6 am to 6 pm

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL

Duration of treatment / exposure:

24 hours before being washed out of the eye

Observation period (in vivo):

upto 72 hours after instillation

Number of animals or in vitro replicates:

3

Details on study design:

At first only one female albino rabbit was exposed to 0.1 mL of the test item in one eye during an initial test. The eye was examined and the changes were graded according to a numerical scale 1 h., 24 h., 48 h. and 72 h. after dosing on day 1 as well as on day 7. Changes ranging from slight to well-defined were observed in the treated eye. Based on these findings two more female albino rabbits were treated with 0.1 mL of the test item each. Likewise ocular defects were graded 1 h., 24 h., 48 h. and 72 h. after dosing on day 1 as well as on day 7. Both of these additional test animals showed changes ranging from slight to well-defined in the treated eyes. All effects were fully reversible within 7 days.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

SCORING SYSTEM:

As per OECD TG 405 - with location of corneal lesions also noted

TOOL USED TO ASSESS SCORE: Hand held inspection lamp fitted with white and UV light and magnifying glass with 2x magnification

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean of scores at 24, 48 and 72hours (+ fluorescein)

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean of scores at 24, 48 and 72hours (+ fluoroscein)

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean of scores at 24, 48 and 72hours (+ fluorescein)

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #1

Time point:

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

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #2

Time point:

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

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

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

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

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

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

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

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

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

Score:

1.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

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

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: max score at 1 hour

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

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

Score:

0.33

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Max score at 1 hour

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 72 hours

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Max score at 1 hour

Irritant / corrosive response data:

One hour after the application of the test item, animals No. 2933 (#1) and No. 2837 (#2) showed scattered or diffuse areas of opacity with details of the iris clearly visible on more than one quarter, but less than half of the cornea area, an iris with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia and existence of reaction to light, a cojunctiva with diffuse crimson colour and individual vessels not easily discernible, an obvious swelling with partial eversion of lids and a flow of tears around the whole eye. In the third animal, No. 2839, scattered or diffuse areas of opacity with details of the iris clearly visible on more than half, but less than three quarters of the cornea area, an iris with markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia and existence of reaction to light, a cojunctiva with diffuse crimson colour and individual vessels not easily discernible, an obvious swelling with partial eversion of lids and a flow of tears around the whole eye were observed.

Twenty-four hours after the application of the test item similar effects were again recorded for all three animals. After the instillation of Fluorescein all three animals showed an easily discernible translucent area with details of the iris slightly obscured on more than half, but less than three quarters of the cornea area.

The following observations undertaken 48 and 72 hours after the application of the test item continued to show the same reactions although some reduction in severity or area of the cornea affected was noticed in some animals. Similarly, the instillation of Fluorescein continued to show some degree of scattered or diffuse areas of opacity, translucent areas and obscuring of iris details at both these investigations in all three animals.

Seven days after the application of the test item animals No. 2933, No. 2837 and No. 2839 were free of any signs of eye irritation.

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on the results of the study described in this report and according to the criteria of the regulation (EC) No 1272/2008, 4-methyl-2-phenylpentan-2-ol is classified as Category 2 "Irritating to eyes" on the basis of corneal opacity scores of greater or equal to 1 (mean values of 1, 1.33 and 2).

Executive summary:

The local effect of 4-methyl-4-phenylpentan-2-ol was investigated according to the method recommended in the OECD Guideline No. 405, "Acute Eye Irritation/ Corrosion", April 2002, the commission directive 2004/73/EC "B.5. Acute Toxicity: Eye Irritation/ Corrosion", April 2004, and the OECD document "Harmonised Integrated Classification System for Human Health and Environmental Hazards of Chemical Substances and Mixtures", August 2001. At first only one female albino rabbit was exposed to 0.1 ml of the test item in one eye during an initial test. The eye was examined and the changes were graded according to a numerical scale 1 h., 24 h., 48 h. and 72 h. after dosing on day 1 as well as on day 7. Changes ranging from slight to well-defined were observed in the treated eye. Based on these findings two more female albino rabbits were treated with 0.1 ml of the test item each. Likewise ocular defects were graded 1 h., 24 h., 48 h. and 72 h. after dosing on day 1 as well as on day 7. Both of these additional test animals showed changes ranging from slight to well-defined in the treated eyes. All effects were fully reversible within 7 days.

Based on the results of the study described in this report and according to the criteria of the regulation (EC) No 1272/2008, 4 -methyl-4 -phenylpentan-2 -ol is classified as Category 2 "Irritating to eyes".

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

4-methyl-4-phenylpentan-2-ol, when tested according to relevant OECD test guidelines, was not irritating to the skin of albino rabbits but displayed mild eye irritation in albino rabbits, sufficient to warrant the classification as an Eye Irritant Category 2 according to EU GHS criteria.

Justification for selection of skin irritation / corrosion endpoint:
GLP study conducted in accordance with OECD TG404 guidelines

Justification for selection of eye irritation endpoint:
GLP study conducted in accordance with OECD TG405 guidelines

Effects on eye irritation: slightly irritating

Justification for classification or non-classification

Skin : under the experimental conditions the mean score for erythema was 1.7 and for oedema 0.3 and, therefore, 4-methyl-4 -phenylpentan-2-ol is non-irritant to the skin.

Eye : corneal opacity scores were greater or equal to 1 (mean values of 1, 1.33 and 2) and, therefore, indicative of an eye irritant Category 2 according to GHS criteria.