4-methyl-4-phenylpentan-2-ol

Eye irritation

Administrative data

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.

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 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye 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 / tissue source

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

Test system

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

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

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

Results 4

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

Results 5

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

Results 6

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

Results 7

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

Results 8

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

Results 9

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

Results 10

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

Results 11

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

Results 12

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.

Applicant's summary and conclusion

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".