3-methylbutanone

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Single ocular exposure followed by a 7 day observation period

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study conducted according to acceptable scientific standards and reviewed by Quality Assurance, although conduct of study according to all aspects of GLP could not be confirmed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

no guideline followed

Deviations:

no

Principles of method if other than guideline:

A single dose of 0.1 mL of methyl isopropyl ketone was placed into the conjunctival sac of the left eye of 6 rabbits. The treated eyes of three rabbits were immediately washed with running distilled water; the eyes of three rabbits were not irrigated. Eyes were evaluated at 1-, 24-, 48-, and 72-h and Days 7 and 14 for the following: conjunctiva, lids, nictitating membrane, corneal opacity, iris, adnexal staining, corneal staining, and discharge. Effects were graded as slight, moderate or strong.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-2-butanone

IUPAC Name:

3-methyl-2-butanone

Constituent 2

Reference substance name:

3-methylbutanone

EC Number:

209-264-3

EC Name:

3-methylbutanone

Cas Number:

563-80-4

Molecular formula:

C5H10O

IUPAC Name:

3-methylbutan-2-one

Constituent 3

Reference substance name:

methylbutanone; methyl isopropyl ketone; MIPK

IUPAC Name:

methylbutanone; methyl isopropyl ketone; MIPK

Details on test material:

-Test substance: Methyl isopropyl ketone
-Date of manufacture: October 1987
-Source: Tennessee Eastman Company

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

no data

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: yes, the right eye served as the control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

3 rabbits: one exposure; the eyes were not irrigated after instillation.
3 rabbits: one exposure; the eyes were immediately washed after instillation.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6 rabbits

Details on study design:

A single dose of 0.1 mL of methyl isopropyl ketone was placed into the conjunctival sac of the left eye of 6 rabbits. The treated eyes of three rabbits were immediately washed with running distilled water; the eyes of the other three rabbits were not irrigated. Eyes were tested with fluorescein dye 24 hours after administration of the test substance. Eyes were evaluated at 1-, 24-, 48-, and 72-h and Days 7 and 14 for the following: conjunctiva, lids, nictitating membrane, corneal opacity, iris, adnexal staining, corneal staining, and discharge. Effects were graded as slight, moderate or strong.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Remarks:

non-numerical descriptors

Basis:

animal: 1, 2, and 3

Time point:

other: 1 h

Score:

> 1 000

Max. score:

1 000

Reversibility:

fully reversible within: Unwashed eyes: 7 days; Washed eyes: 72 hours

Remarks on result:

other: At 1-h: moderate irritation of the conjunctiva and nictitating membrane, slight irritation of the lids, slight discharge in unwashed eyes; moderate irritation of the conjunctiva and nictitating membrane and slight discharge also seen in washed eyes.

Results 2

Irritation parameter:

overall irritation score

Remarks:

non-numerical descriptors

Basis:

animal: 1, 2, and 3

Time point:

other: 24 h

Score:

> 1 000

Max. score:

1 000

Reversibility:

fully reversible within: Unwashed eyes: 7 days; Washed eyes: 72 hours

Remarks on result:

other: At 24-h: moderate irritation of conjunctiva and nictitating membrane, slight irritation of lids, slight corneal opacity, adnexal staining, corneal staining (1/3), slight discharge in unwashed eyes; irritation in washed eyes was slight.

Results 3

Irritation parameter:

overall irritation score

Remarks:

non-numerical descriptors

Basis:

animal: 1, 2, and 3

Time point:

other: 48 h

Score:

> 1 000

Max. score:

1 000

Reversibility:

fully reversible within: Unwashed eyes: 7 days; Washed eyes: 72 hours

Remarks on result:

other: At 48-h: slight irritation of conjunctiva, lids, and nictitating membrane, slight corneal opacity, slight discharge in unwashed eyes; 2/3 washed eyes were normal, slight irritation of conjunctiva and nictitating membrane seen 1/3.

Results 4

Irritation parameter:

overall irritation score

Remarks:

non-numerical descriptors

Basis:

animal: 1, 2, and 3

Time point:

other: 72 h

Score:

> 1 000

Max. score:

1 000

Reversibility:

fully reversible within: Unwashed eyes: 7 days; Washed eyes: 72 hours

Remarks on result:

other: At the 72-h observation period, 1/3 unwashed eyes was normal and remaining effects were limited to slight irritation of the conjunctiva and nictitating membrane in the other eyes; all washed eyes were normal.

Irritant / corrosive response data:

No numerical scores were provided in the study. Irritation was rated on a descriptive scale as slight, moderate or strong. In unwashed eyes, the test substance caused moderate edema and erythema of the conjunctivae and nictitating membranes and slight discharges from all eyes. Slight erythema (2/3) and slight edema (1/3) of the lids were also noted in unwashed eyes. When tested with fluorescein dye 24 hours after dosing, staining of the nictitating membranes of all eyes was evident. Staining of the cornea, lids, and conjunctivae was also noted in one of three unwashed eyes. By 48 hours, the irritant responses were judged to be only slight; at 72 hours, effects were only seen on the conjunctivae and nictitating membranes of two animals, and were graded only as slight (Grade 1) irritation. One eye was normal at 72 hours. By day 7, all unwashed eyes appeared clinically normal.

In washed eyes, signs of irritation were restricted to slight to moderate erythema (3/3) and moderate edema (2/3) of the conjunctivae and nictitating membranes. Slight discharges were noted from two of three washed eyes only at 1 hour post dosing. No corneal or adnexal staining was evident when the eyes were tested with fluorescein dye 24 hours after administration of the test substance. At 24 and 48 hours, effects were graded only as slight (Grade 1) irritation of the conjunctivae and nictitating membranes. Two of three washed eyes were normal by 48 hours and by 72 hours, all washed eyes appeared clinically normal.

Any other information on results incl. tables

Note that the value of "1000" under max sscore is meaningless. This number was used as a placeholder as IUCLID 5 requires a numerical value, and no such values were used in the study.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Although some subjective irritant responses were seen when methyl isopropyl ketone was placed in the eyes of New Zealand White rabbits under the conditions used in this study, the criteria for classifying the substance as an ocular irritant (Corneal opacity or iritis of 1 or greater or conjunctival redness or edema of 2 or greater, averaged over 24, 48, and 72 hours) under GHS were not met.

Based on the finding that an acute ocular exposure to methyl isopropyl ketone in New Zealand White rabbits produced irritation which rapidly resolved, methyl isopropyl ketone is not classified for "Serious Eye Damage/ Eye Irritation" under GHS.

Executive summary:

In an eye irritation study, 0.1 mL of methyl isopropyl ketone was administered into the conjunctival sac of one eye of each of six New Zealand White Rabbits. Immediately after instillation, the eyes of three rabbits were washed with running distilled water while the eyes of the other three rabbits were not irrigated. The eyes were examined for 7 days post-instillation for signs of irritation.

  

Effects in the unwashed eyes included moderate edema and erythema of the conjunctivae and nictitating membranes and slight discharges from all eyes for the first 24 hours; slight erythema and slight edema of the lids was also noted in one or more eyes. When tested with fluorescein dye at the 24-h examination, a number of ocular tissues were stained in one or more eyes. The irritant effects of the test substance were reduced to slight by 48 hours post-dosing. By 72 hours, one eye was completely normal and the other unwashed eyes were normal by 7 days. Although the initial responses demonstrated the presence of moderate subjective eye irritation at 24 hours, the observed responses averaged over 24, 48, and 72 hours were not sufficient to label the substance as irritating to eyes under GHS criteria.

  

Immediate washing of eyes significantly reduced the observed irritant responses and eliminated staining of ocular tissues by fluorescein. Two of three washed eyes were completely normal by 48 hours and the third eye was normal by 72 hours post-dosing.