4,4'-dioxo-4,4'-dioxydibutyric acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1996-06-07 to 1996-08-29

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-dioxo-4,4'-dioxydibutyric acid

EC Number:

204-611-5

EC Name:

4,4'-dioxo-4,4'-dioxydibutyric acid

Cas Number:

123-23-9

Molecular formula:

C8H10O8

IUPAC Name:

4-[(3-carboxypropanoyl)peroxy]-4-oxobutanoic acid

Test material form:

liquid

Specific details on test material used for the study:

Lot No.: 0998603612
Purity: 59.6 %

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Myrtle's Rabbitry, Thompson Station, TN, USA
- Age at study initiation: adult
- Weight at study initiation: approximately 2.0 to 3.5 kg
- Housing: individually in suspended stainless steel cages
- Diet: PMI Certified Rabbit Chow #5322 (Purina Mills, Inc.) was provided ad libitum to the animals throughout the study.
- Water: Municipal tap water treated by reverse osmosis was available ad libitum throughout the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 - 20 °C (67 - 68 °F)
- Humidity (%): 62 - 85
- Air changes (per hr): 10 - 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

100 % concentration; 0.1 g substance were instilled

Duration of treatment / exposure:

Single dosage with no rinse.

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

1 female rabbit

Details on study design:

The test article was instilled into the conjunctival sac of the right eye of the animal after gently pulling the lower lid away from the eye. Following instillation, the eyelids were gently held together for approximately one second in order to limit test article loss and the animal was returned to its cage. The contralateral eye remained untreated to serve as a control.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

48 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

2

Reversibility:

not reversible

Results 5

Irritation parameter:

iris score

Basis:

animal #1

Time point:

48 h

Max. score:

2

Remarks on result:

not determinable

Remarks:

due to degree of opacity

Results 6

Irritation parameter:

iris score

Basis:

animal #1

Time point:

72 h

Max. score:

2

Remarks on result:

not determinable

Remarks:

due to degree of opacity

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: conjunctival redness

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: conjunctival redness

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: conjunctival redness

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: conjunctival swelling

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

48 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: conjunctival swelling

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: conjunctival swelling

Irritant / corrosive response data:

Exposure to the test article produced corneal opacity in the test eye at the 1 hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24 hour scoring interval. Iritis was observed in the test eye at the 1 hour scoring interval. Conjunctivitis (redness and swelling) was noted in the test eye at the 1 hour scoring interval. Additional ocular findings of blanching of nictating membrane, blanching of conjunctival tissue, ocular discharge-yellow and head tilt were noted in the test eye. Due to the severe irritation noted, the animal was euthanized following the 72 hour score.
No corneal opacity, iritis or conjunctivitis was observed in the control eyes.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

Based on the initial rabbit dosed, the test item is considered to be a corrosive to the ocular tissue of the rabbit.

Executive summary:

The potential irritant and/or corrosive effects of the test item were evaluated on the eyes of New Zealand White rabbits. One rabbit received a 0.1000 g (0.1 mL weight equivalent) dose of the test item in the conjunctival sac of the right eye. The contralateral eye of the animal remained untreated and served as a control. The test and control eye was examined for signs of irritation for up to 72 hours following dosing. Due to the amount of irritation noted in the initial rabbit, the remaining animals were not dosed.

Exposure to the test article produced corneal opacity in the test eye at the 1 hour scoring interval. The corneal injury was confirmed by positive fluorescein dye retention at the 24 hour scoring interval. Iritis was observed in the test eye at the 1 hour scoring interval. Conjunctivitis (redness and swelling) was noted in the test eye at the 1 hour scoring interval. Additional ocular findings of blanching of nictating membrane, blanching of conjunctival tissue, ocular discharge-yellow and head tilt were noted in the test eye. Due to the severe irritation noted, the animal was euthanized following the 72 hour score.

Based on the initial rabbit dosed, the test item is considered to be a corrosive to the ocular tissue of the rabbit.