Isopropyl acetoacetate

Endpoint summary

Description of key information

The test item showed no skin irritation potential in an in vivo study in rabbits (reference 7.3.1-1).

The test item showed eye irritating properties in an in vivo study in rabbits (reference 7.3.2-1).

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

Study period:

1988-01-12 to 1988-01-15

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1984-04-25

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1981-05-12

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HOECHST AG
- Age at study initiation: ca. 3-5 months
- Weight at study initiation: 2.7 - 3.0 kg
- Housing: individual cages
- 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

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 mL

Duration of treatment / exposure:

4 h

Observation period:

72 h

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: 2.5 x 2.5 cm area covered with a band aid, in a ca. 25 cm² clipped area on the dorsal trunk of each rabbit
- Type of wrap: band aid covered with a semiocclusive bandage

REMOVAL OF TEST SUBSTANCE
- Washing: yes, with lukewarm tap water
- Time after start of exposure: after exposure time of 4 h

OBSERVATION TIME POINTS
30 minutes and 1, 24, 48 and 72 h after exposure

SCORING SYSTEM:
Erythema and eschar formation:
0: no erythema
1: slight, barely perceivable, erythema
2: well-defined erythema
3: mild to severe erythema
4: severe erythema (intense redness) to formation of eschar (penetrative injury)

Edema formation:
0: no edema
1: slight, barely perceivable, edema
2: slight edema (with swelling at well-defined boundary)
3. mild edema (swelling ca. 1 mm)
4. severe edema (swelling of more than 1 mm and larger than exposure area)

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 h

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 h

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effect observed.

Other effects:

No further effects were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item showed no skin irritation potential in a in vivo study in rabbits.

Executive summary:

The skin irriation potential of the test item was evaluated using an in vivo study according to OECD 404 in three rabbits. The undiluted test item was applied to a clipped area on the dorsal trunk of the animals under semiocclusive cover. The exposure time was 4 hours. Afterwards residual test item was removed by washing with lukewarm water. The test site was evaluated after 30 minutes and 1, 24, 48 and 72 hours. The animals showed a mean erythema score for 24/48/72 h of 0.9 with no individual animal scoring higher than 1.0. The mean edema score for 24/48/72 h was 0.1 with the mean score for one animal at 0.3 and 0.0 for the remaining two animals. All effects observed were reversible within 72 h. Based on the results of the in vivo study in rabbits the test item was determined not to cause skin irritation or corrosion.

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

Study period:

1988-01-19 to 1988-01-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

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

Version / remarks:

1984-01-25

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987-02-24

Deviations:

no

GLP compliance:

yes

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

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

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No effect observed

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

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

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: No effect observed

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

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

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 d

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

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

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.

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.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The skin irritation potential of the test item was evaluated using an in vivo study according to OECD 404 in three rabbits. The undiluted test item was applied to a clipped area on the dorsal trunk of the animals under semiocclusive cover. The exposure time was 4 hours. Afterwards residual test item was removed by washing with lukewarm water. The test site was evaluated after 30 minutes and 1, 24, 48 and 72 hours. The animals showed a mean erythema score for 24/48/72 h of 0.9 with no individual animal scoring higher than 1.0. The mean edema score for 24/48/72 h was 0.1 with the mean score for one animal at 0.3 and 0.0 for the remaining two animals. All effects observed were reversible within 72 h. Based on the results of the in vivo study in rabbits the test item was determined not to cause skin irritation or corrosion.

Eye irritation

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.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on skin irritation, the test item does not require classification for skin irritation according to Regulation (EC) No 1272/2008 (CLP), as amended for the fifteenth time in Regulation (EU) 2020/1182.

Based on available data on eye irritation, the test item requires classification for skin irritation Cat. 2 (H319: Causes serious eye irritation) according to Regulation (EC) No 1272/2008 (CLP), as amended for the fifteenth time in Regulation (EU) 2020/1182.