Methyl acetoacetate

Eye irritation

Administrative data

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: Guideline study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl acetoacetate

EC Number:

203-299-8

EC Name:

Methyl acetoacetate

Cas Number:

105-45-3

Molecular formula:

C5H8O3

IUPAC Name:

methyl 3-oxobutanoate

Details on test material:

- Name of test material (as cited in study report): Acetessigsäuremethylester (methyl acetoacetate),
- Substance number: 83/114
- Analytical purity: no data
- Expiration date of the lot/batch: April 1985

Test animals / tissue source

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach am Main, Germany
- Age at study initiation: no data
- Weight at study initiation: Two females (mean weight, 2.92 kg) and one male (2.74 kg)
- Housing: single
- Diet (e.g. ad libitum): Ovator Solikanin 4 mm, Muskator-Werke, Duesseldorf, ca 130 g / animal / day
- Water (e.g. ad libitum): ca. 250 ml tap water / animal / day
- Acclimation period: at least 8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12 h / 12 h

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye of each animal remained untreated and served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
- Concentration (if solution): undiluted

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

8 days

Number of animals or in vitro replicates:

3 (1 male; 2 females)

Details on study design:

TREATMENT
- One tenth millilitre of the undiluted test substance was instilled into the conjunctival sac of the right eye lid of each rabbit.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was not washed out.

READINGS
Following application, readings of the eyes were performed at 1, 24, 48 and 72 hours after instillation and at 8 days after instillation. The rabbits were also observed for their general condition.

SCORING SYSTEM
- The assessment of the ocular lesions was based on the scoring of JH Draize, Appraisal of the saftey of chemicals in foods, drugs, and cosmetics. In dermal toxicity pp. 46-59, 1959.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

4

Reversibility:

not fully reversible within: 8 days (score 1)

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 5

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 6

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

1.67

Max. score:

2

Reversibility:

fully reversible within: 8 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 8 days

Results 10

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24, 48 and 72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 11

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 12

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24, 48 and 72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 8 days

Irritant / corrosive response data:

Findings after 1 hour: A slight corneal opacity was reported. The conjunctivae displayed noticeable to severe redness and swelling, with slight to noticeable lacrimation (all animals). In one animal the pupil of the rabbit was constricted.

Findings after 24 hours: Corneal opacity still persisted in all rabbits, and in one animal, it even had become more conspicuous than the 1-hour finding. The conjunctivae still displayed noticeable to severe redness; however, swelling had improved to slight degree in two animals. Slight to noticeable lacrimation was still seen in all animals. Ciliary injection of the iris was observed in all three rabbits. The rabbits had narrowed pupils; suppuration and scarring within the eyelid was reported for one animal.

Findings after 48 hours: Slight to severe corneal opacity still persisted seen in two of the three rabbits; in one rabbit, corneal opacity had disappeared. Slight to noticeable redness of the conjunctivae persisted in all animals. Swelling of a slight degree was noted in two animals; no edema was reported for the third animal. The incidence of lacrimation was similar to those reported at 24 hours. In two animals, ciliary injection had developed into iritis; the remaining rabbit still displayed ciliary injection within the iris. All the rabbits had narrowed pupils; scarring within the eyelid was seen in one rabbit, scarring with suppuration was seen in another animal.

Findings after 72 hours: With exception of ciliary injection, the treated eye of one rabbit had completely recovered at this time point. For the remaining two rabbits, incidence and severity of both corneal and iritic effects were similar to those reported at 48 hours. Conjunctivae redness persisted in one rabbit; conjunctival redness, edema, and lacrimation persisted in another rabbit. Both rabbits still had narrowed pupils and scarring of the eyelid without and with suppuration, respectively.

Findings after 8 days: After 8 days the treated eyes of two rabbits showed no more effects within the cornea, conjunctivae and iris; however, scarring of the eyelid was still present in one of these two animals. The third animal still displayed slight corneal opacity affecting less than 1/4 of the corneal surface, narrowed pupil and scarring of the eyelid.

Other effects:

No other effects were observed.

Any other information on results incl. tables

Animal	Reading	Cornea	Iris	Conjunctiva		Additional findings
		Opacity		Redness	Chemosis
1	1 h	1	1	3	2	constricted pupil
2	1 h	1	0	2	2	constricted pupil
3	1 h	1	0	3	3	constricted pupil
1	24 h	1	1	2	1	constricted pupil
2	24 h	1	1	2	1	constricted pupil
3	24 h	2	1	3	2	constricted pupil, ulceration, scarred retraction at the eyelid
1	48 h	1	2	2	1	constricted pupil, scarred retraction at the eyelid
2	48 h	0	1	1	0	constricted pupil
3	48 h	2	2	2	1	constricted pupil, ulceration, scarred retraction at the eyelid
1	72 h	1	2	2	0	constricted pupil
2	72 h	0	1	0	0	scarred retraction at the eyelid
3	72 h	2	2	2	1	constricted pupil, ulceration, scarred retraction at the eyelid
1	8 d	0	0	0	0	constricted pupil
2	8 d	0	0	0	0
3	8 d	1	0	0	0	constricted pupil, ulceration
mean animal 1	24 - 72 h	1.00	1.67	2.00	0.67
mean animal 2	24 - 72 h	0.33	1.00	1.00	0.33
mean animal 3	25 - 72 h	2.00	1.67	2.33	1.33
mean	24 - 72 h	1.11	1.44	1.78	0.78

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU