Isopropyl acetoacetate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1988-01-19 to 1988-01-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

1984-01-25

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isopropyl acetoacetate

EC Number:

208-798-4

EC Name:

Isopropyl acetoacetate

Cas Number:

542-08-5

Molecular formula:

C7H12O3

IUPAC Name:

propan-2-yl 3-oxobutanoate

Test material form:

liquid

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG
- Age at study initiation: ca 3 - 5 months
- Weight at study initiation: 2.1 - 3.2 kg
- Housing: single
- Diet: ad libitum, rabbit diet Altromin 2123 and hay
- Water: ad libitum, deionised and chlorinated water
- Acclimation period: not detailed

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 50 ± 20
- Air changes (per hr): not detailed, but air condition in animal rooms
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with ohysiological saline at ca. 37 °C
- Time after start of exposure: after 24 h and for each evaluation if discharge was observed, and after treatment with fluorescein solution (0.01 %)

SCORING SYSTEM:
Cornea
Opacity: degree of density (readings should be taken from most dense area)
0: No ulceration or opacity
1: Scattered or diffuse areas of opacity (other than slight dulling of normal lustre); details of iris clearly visible
2: Easily discernible translucent area; details of iris slightly obscured
3: Nacrous area; no details of iris visible; size of pupil barely discernible
4: Opaque cornea; iris not discernible through the opacity

Iris
0: Normal
1: Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia; or injection; iris reactive to light (a sluggish reaction is considered to be an effect)
2: Hemorrhage, gross destruction, or no reaction to light (all or one of the symptoms)

Conjunctivae
Redness: lids and/or nictating membranes
0: Normal
1: Some blood vessels hyperaemic (injected)
2: Diffuse,crimson colour; individual vessels not easily discernible
3: Diffuse beefy red

Chemosis
Swelling: lids and/or nictating membranes
0: Normal
1: Some swelling above normal (incl. nictating membranes)
2: Obvious swelling, with partial eversion of lids
3: Swelling, with lids about half closed
4: Swelling, with lids more than half closed

TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effect observed

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: No effect observed

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

2

Reversibility:

fully reversible within: 48 h

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 h

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

The conjunctivae showed very slight swelling to swelling with lids about half closed from one to 24 hours after treatment. In addition it was crimson coloured to beefy red and the iris was redden and a diffuse opacity of the cornea was detected. 48 hours after application effects reached from some hyperaemic blood vessels to diffuse,crimson colour of the conjunctivae. One animal presented with a barely perceivable swelling of the conjunctivae. In two animals some hyperaemic blood vessels could still be observed 72 hours after treatment. Within the first 24 hours clear, colourless discharge accompanied some of the observed effects. At the examination 7 days after treatment no effects were detected.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

The test item showed eye irritating properties in rabbits.

Executive summary:

In a study according to OECD 405 the potential of the test item to induce eye irritation or corrosion was determined. Therefore, the test item was instiled into each one eye of three rabbits. The other eye was used as untreated control. After 24 h the eye was rinsed and the effects were evaluated after 1, 24, 48 and 72 hours and after 7 days. The conjunctivae showed very slight swelling to swelling with lids about half closed from one to 24 hours after treatment. In addition it was crimson coloured to beefy red and the iris was redden and a diffuse opacity of the cornea was detected. 48 hours after application effects reached from some hyperaemic blood vessels to diffuse,crimson colour of the conjunctivae. One animal presented with a barely perceivable swelling of the conjunctivae. In two animals some hyperaemic blood vessels could still be observed 72 hours after treatment. Within the first 24 hours clear, colourless discharge accompanied some of the observed effects. At the examination 7 days after treatment no effects were detected. Based on two animals showing a conjunctivae score of 2.0 for 24/48/72 h the test item is considered to cause eye irritation.