4-methylpentan-2-ol

Eye irritation

Administrative data

Endpoint:

eye 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:

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

Version / remarks:

1992

Deviations:

yes

Remarks:

- highest temperature recorded was 26 °C vs. 20 ± 3 °C range recommended

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

- highest temperature recorded was 26 °C vs. 20 ± 3 °C range recommended

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Ltd., Bicester, Oxon, England.
- Age at study initiation: At least 11 weeks of age.
- Weight at study initiation: 2.3 to 2.9 kg.
- Housing: Housed individually in metal 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 by Anglian Water, ad libitum.
- Acclimation period: A minimum period of 19 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.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL.
- Concentration (if solution): As supplied by the Sponsor.

Duration of treatment / exposure:

After instillation of the test substance, the eyelid was gently held together for 1 second before releasing (single exposure).

Observation period (in vivo):

1 hour and 1, 2, and 3 days after instillation. Additional observations were made 4.5 hours after instillation in 2 animals, 4 through 7 days after instillation in all 3 animals and 8 through 14 days after instillation in one animal.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No.


SCORING SYSTEM:
Ocular opacity: degree of density (area most dense taken for reading)

No ulceration or opacity: 0
Scattered or diffused areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible: 1
Easily discernible translucent areas, details of iris slightly obscured: 2
Nacreous areas, no details of iris visible, size of pupil barely discernible: 3
Opaque cornea, iris not discernible through the opacity: 4

Area of corneal involved:

None: 0
One quarter (or less) but not zero: 1
Greater than one quarter, but less than half: 2
Greater than half, but less than three quarters: 3
Greater than three quarters, up to whole area: 4

Iris:

Normal: 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive): 1
No reaction to light, haemorrhage, gross destruction (any or all of these): 2

Conjunctivae Redness: (refers to the most severe reading of palpebral and bulbar conjunctivae, as compared to the control eye)

Blood vessels normal: 0
Some blood vessel definately hyperaemic (injected): 1
Diffuse, crimson colour, individual vessels not easily discernible: 2
Diffuse beefy red: 3

Chemosis: (lids and/or nictating membranes)

No swelling: 0
Any swelling above normal (includes nictating membranes): 1
Obvious swelling with partial eversion of lids: 2
Swelling with lids about half-closed: 3
Swelling with lids more than half-closed: 4

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



TOOL USED TO ASSESS SCORE: handheld light.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 3 days

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

2.3

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 and 72 hours

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 3 days

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 3 days

Results 6

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 3 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 8

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Results 9

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Dulling of the cornea observed 1 and 4.5 hours after instillation

Results 10

Irritation parameter:

iris score

Time point:

other: Days 1 and 2

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 7 days

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

1.3

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48 and 72 hours

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritant / corrosive response data:

Corneal opacification (Grade 1 or 2) developed in all 3 animals. Iridial inflammation (Grade 1) was observed in all 3 rabbits. A diffuse beefy red or crimson colouration of the conjunctivae and swelling with eyelids about half-closed was seen in all three animals. These reactions had resolved by either 7 or 14 days after instillation.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information CLP category 2 or R36 Criteria used for interpretation of results: EU

Executive summary:

An eye irritation study on methyl iso butyl carbinol has been performed in accordance with OECD Guidelines for the Testing of Chemicals No. 405 and in compliance with GLP.  In this study, 0.1 mL of undiluted methyl iso butyl carbinol was instilled into one conjunctival sac of each of 3 New Zealand White rabbits.  Ocular changes were assessed 1, 4.5, 24, 48, 72 hours after treatment, and additional daily observations were made up to a maximum of 14 days.  Eye irritation reactions were observed and scored according to guideline methods.  No clinical signs of systemic toxicity or ill health were observed in any rabbit during the course of the study.  Corneal opacification (Grade 1 or 2), iridial inflammation (Grade 1), and a diffuse beefy red or crimson coloration of the conjunctivae and swelling with eyelids about half-closed were observed in all animals. These effects were resolved within 7 or 14 days after instillation. Under the conditions of this study, methyl iso butyl carbinol induced corneal opacification, iridial inflammation, and conjunctival irritation. Individual mean scores over 24, 48 and 72 hours were 1.0, 0.7 and 2.0 for corneal opacity, 0.7, 0.7 and 0.3 for iritis, 2.3, 1.3 and 1.3 for conjunctival redness and 1.0, 0.3 and 0.3 for chemosis.