Methyl acetoacetate

Endpoint summary

Description of key information

The test item MAA was tested for skin and irritation on rabbits. In the key study according to OECD Guideline 404 (Acute dermal irritation / corrosion) similar or equivalent to EU Method B.4. The test item was not irritant to the skin of the rabbit and no corrosive effects were noted. In the key study according to OECD Guideline 405 (Acute eye irritation / corrosion) similar or equivalent to EU Method B.5), MAA showed severe irritating effects on cornea, conjunctiva and iris. Opacity of the cornea persisted in one animal until the end of the observation period of 21 days. Based on these effects. MAA has to be classified as severe eye-irritant - Category 1 (irreversible effect on the eye). There is no data available on respiratory irritation. However, there is no indication for respiratory irritation from handling and use. 

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:

May 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study performed in accordance with the corresponding OECD-/EU-testing guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- number of animals: 3
- Weight at study initiation: 2200-2600 mg/kg
- Housing: single housing

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml test item was applied on a 2.5 x 2.5 cm patch

Duration of treatment / exposure:

4 hours

Observation period:

Observation 30 minutes, 24 hours, 48 hours and 72 hours after removal of patch

Number of animals:

3 animals

Details on study design:

no data

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

1

Reversibility:

fully reversible within: 48 h

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Only very slight erythema in all animals and very slight oedema in one animal were observed. 2 out of three animals showed a slight redness of the application site 30 minutes after removal of the patch. All findings were completely reversible within 48 hours.

Other effects:

None

The results are summarized below:

 

Observation	Mean values over 24, 48 & 72 hours			Mean value
	No.1	No.2	No.3
Erythema	0.3	0.3	0	0.2
Oedema	0	0	0	0

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance was classified as non-irritant to skin.

Executive summary:

The study was performed in 1983 under GLP according to OECD 404. Three albino rabbits were treated semi-occlusive with 0.5 ml test item was applied on a 2.5 x 2.5 cm patch. Observation times were 24, 48 and 72 hours after removal of the patch. Only very slight erythema in all animals and very slight oedema in one animal were observed. 2 out of three animals showed a slight redness of the application site 30 minutes after removal of the patch. All findings were completely reversible within 48 hours. Therefore, MAA is not irritating to rabbit skin.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study performed in accordance with the corresponding OECD-/EU-testing guidelines

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- number of animals: 3
- Weight at study initiation: 2200-2600 mg/kg
- Housing: single housing

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Amount applied: 0.1 ml

Duration of treatment / exposure:

Duration of treatment was 24 hours

Observation period (in vivo):

Obervations were done at 1, 24, 48 and 72 hours and 7, 14 and 21 days after application

Number of animals or in vitro replicates:

3 animals were used in this study

Details on study design:

The treated eyes were rinsed 24 hours after application.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Max. score:

2.3

Reversibility:

not fully reversible within: 21 days

Remarks on result:

other: cornea opacity with vascularization

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.3

Max. score:

2.7

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.8

Max. score:

2.3

Reversibility:

fully reversible within: 21 days

Irritant / corrosive response data:

The test item showed severe irritating effects in this test. The effects on conjunctiva (chemosis and redness) and on iris were found to be reversible within 21 days after treatment. The cornea opacity incl. vascularization observed in one animal persisted in one animal until the end of the observation period and was therefore not reversible.

Other effects:

Strong clear or slimy secretion was noted in the treated eyes of all animals up to 72 hours after application. The animal with irreversible opacity of thecornea showed also vascularization from day 7 until the end of the observation period of 21 days.

See table above.

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test item is severely irritating and caused irreversible effects on the cornea. Therefore, it has to be classified as Category 1 eye-irritant.

Executive summary:

The study was performed in 1983 under GLP according to OECD 405. Three albino rabbits were treated; 0.1 ml test item was applied into the conjunctival sac of the eye. Observation times were 1, 24, 48 and 72 hours and 7, 14 and 21 days after treatment .

The test item showed severe irritating effects in this test. The effects on conjunctiva (chemosis and redness) and on iris were found to be reversible within 21 days after treatment. The cornea opacity incl. vascularization observed in one animal persisted in one animal until the end of the observation period and was therefore not reversible. In conclusion, MAA needs to be classified as Category 1 eye-irritant.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Key – Skin irritation

A study was performed in 1983 as GLP-study according to OECD 404. Three albino rabbits were treated semi-occlusive with 0.5 ml test item was applied on a 2.5 x 2.5 cm patch. Observation times were 24, 48 and 72 hours after removal of the patch. Only very slight erythema in all animals and very slight oedema in one animal were observed. 2 out of three animals showed a slight redness of the application site 30 minutes after removal of the patch. All findings were completely reversible within 48 hours. Therefore, MAA is not irritating to rabbit skin.

Supporting – Skin irritation

Another study was performed in 1974, following the DOT (Transport Classification) Guidelines. A couple of substances were tested in one study. The intact and abraded skin of 138 albino rabbits was employed for this study. A series of 6 rabbits was used for testing each substance. The patches consisted of 1.5 inch x 1.5 inch 12 ply gauze squares. The patches were secured to the area by thin bands of adhesive tape (occlusive application). The material to be tested (0.5 ml, was introduced beneath the patch. The entire trunks of the animals were then wrapped in clear plastic trunk bands. Only very slight erythema (score 1) was noted in all 6 animals 4h hours after removal of the patch. No oedema were observed. These findings were completely reversible within 24 hours. MAA is considered to be not irritating to rabbit skin.

Key - Eye irritation

The study was performed in 1983 under GLP according to OECD 405. Three albino rabbits were treated; 0.1 ml test item was applied into the conjunctival sac of the eye. Observation times were 1, 24, 48 and 72 hours and 7, 14 and 21 days after treatment . The test item showed severe irritating effects in this test. The effects on conjunctiva (chemosis and redness) and on iris were found to be reversible within 21 days after treatment. The cornea opacity incl. vascularization observed in one animal persisted in one animal until the end of the observation period and was therefore not reversible. In conclusion, MAA needs to be classified as Category 1 eye-irritant.

Waiver - Respiratory irritation

There is no data available on respiratory irritation.

Justification for selection of skin irritation / corrosion endpoint:
Guideline study; Klimisch 1

Justification for selection of eye irritation endpoint:
Guideline study; Klimisch 1

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

The skin irritation study did not reveal any irritating effects, therefore MAA is not irritant to rabbit skin. The eye irritation test showed severe irritating effects on cornea, conjunctiva and iris. Opacity of the cornea persisted in one animal until the end of the observation period of 21 days. Based on these effects. MAA has to be classified as severe eye-irritant - Category 1 (irreversible effect on the eye).