2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

22 February, 2000 to 3 March, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

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

GLP compliance:

yes (incl. QA statement)

Remarks:

Swiss GLP

Test material

Test material information

Constituent 1

Reference substance name:

2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate

EC Number:

254-959-7

EC Name:

2-[(1-amino-9,10-dihydro-4-hydroxy-9,10-dioxo-2-anthryl)oxy]ethyl ethyl carbonate

Cas Number:

40530-60-7

Molecular formula:

C19H17NO7

IUPAC Name:

2-[(1-amino-4-hydroxy-9,10-dioxo-9,10-dihydroanthracen-2-yl)oxy]ethyl ethyl carbonate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

-Identification: FAT 93503/A.
-Item N°: 0033275.
-Vers. N°: 99 Labor Mischung 1.
-Purity: Approximately 96%.
-Color / Physical state: Red powder.
-pH (1g/l): 7-8.
-Expiry date: January 2005.
-Storage condition: In the original container, at room temperature (range of 20 +/- 3 °C), away from direct light.
-Safety precautions: Gloves, goggles and face mask were sufficient to assure personnel health and safety.

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 99 Labor Mischung 1
- Expiration date of the lot/batch: January 2005

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In the original container, at room temperature (range of 20 ± 3 °C), away from direct sunlight.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Test system: New Zealand White Rabbit, SPF.
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne / France.
- Age at study initiation: 14 weeks (male) and 14 to 15 weeks (females).
- Weight at study initiation: approximately 3.0 to 3.2 kg.
- Housing: Individually in stainless steel cages equipped with feed hoppers.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 66/99) provided by Provimi Kliba AG, CH-4303 Kaiseraugst.
- Water: Community tap water from Füllinsdorf ad libitum.
- Acclimation period: Seven days under laboratory conditions after health examination. only animals without any visual signs of illness were used for the study.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 28-52 %
- Air changes: Air-conditioned with 10-15 air changes per hour.
- Photoperiod: Light cycle of 12 h light and 12 h dark. Music was played during the light cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 g (per animal) of FAT 93503/A was weighed and applied undiluted as it was delivered by the sponsor.

Duration of treatment / exposure:

single application

Observation period (in vivo):

72 h

Number of animals or in vitro replicates:

1 male and 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Grading of Ocular Lesions.
CORNEA.
- No ulceration or opacity: 0
- Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible: 1
- Easily discernible translucent area, details of iris slightly obscured: 2
- Nacreous area, no details of iris visible, size of pupil barely discernible: 3
- Opaque cornea, iris not discernible through the opacity: 4

IRIS
- Normal: 0
- Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination of any thereof, iris still reacting to light (sluggish reaction is positive): 1
- No reaction to light, haemorrhage, gross destruction (any or all of these): 2

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with control eye)
- Blood vessels normal: 0
- Some blood vessels definitely hyperemic (injected): 1
- Diffuse, crimson color, individual vessels not easily discernible: 2
- Diffuse beefy red: 3

Chemosis: lids and/or nictitating membranes
- No swelling: 0
- Any swelling above normal (including nictitating membranes): 1
- Obvious swelling with partial eversion of lids: 2
- Swelling with lids about half-closed: 3
- Swelling with lids more than half-closed: 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Remarks:

Male (animal no 19)

Time point:

24/48/72 h

Score:

0

Max. score:

3

Results 4

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Remarks:

Female (animal no 20)

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 5

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Remarks:

Female (animal no 21)

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 h

Results 6

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

3 animal

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

IRRITATION:
Application of the test article to healthy rabbit conjunctivae resulted in a primary irritation score of 0.56. The eye reactions (mean values from 24 to 72 h) consisted of grade 0 corneal opacity, grade 0.00 iris, grade 0.56 redness of the conjunctivae and grade 0 Chemosis of the conjunctivae. Hyperemic conjunctival blood vessels were noted in all animals at the 1-hour examination and persisted through 48 h (one animal), increased in severity at 24 h before diminishing to clear by 72 h (one animal) or disappeared at the 24-h examination (one animal). Slight conjunctival swelling was seen in two animals at the 1-h examination. Slightly to moderately reddened sclera was observed in all animals at the 1-h reading and persisted with less severity in one animal through 48 h. All eye reactions were clear within 72 h after treatment.

CORROSION:
No corrosion of the cornea was observed at any of the reading times.

Other effects:

VIABILITY/MORTALITY AND CLINICAL SIGNS:
- No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.

COLORATION
Red to light red staining of the treated eyes by the test article was observed during the entire reading period.
Red remnants of the test article in eye or conjunctival sac were observed at the 1-h reading.

BODY WEIGHTS
Except the slight loss of body weight of the animal no. 21 (Female) between the treatment start and the end of the study, the body weight of the rabbits were considered to be within the normal range of variability. This loss of body weight was considered to be incidental.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 93503/A is considered to be not irritating to the rabbit eye.

Executive summary:

The purpose of this primary eye irritation study was to assess the possible irritation potential when a single dose of the test article is placed in the conjunctival sac of rabbit eyes. The study was conducted according to the OECD Guideline 405 (Acute Eye Irritation / Corrosion). The primary irritation potential of FAT 93503/A was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. The treated eyes were not rinsed after application. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 h after test article application. The scores of each animal at the following reading times (24, 48 and 72 h) were used in calculating the respective mean values for each type of lesion. The primary irritation score was calculated by totalling the individual cumulative scores at 24, 48 and 72 h and then dividing the resulting total by the number of data points. The primary irritation score was 0.56 (max. 13). The eye reactions (mean values from 24 to 72 h) consisted of grade 0 corneal opacity, grade 0 iris, grade 0.56 redness of the conjunctivae and grade 0 chemosis of the conjunctivae. Hyperemic conjunctival blood vessels were noted in all animals at the 1-h examination and persisted through 48 h (one animal), increased in severity at 24 h before diminishing to clear by 72 h (one animal) or disappeared at the 24-h examination (one animal). Slight conjunctival swelling was seen in two animals at the 1-h examination. Slightly to moderately reddened sclera was observed in all animals at the 1-h reading and persisted with less severity in one animal through 48 h. All eye reactions were clear within 72 h after treatment. Red to light red staining of the treated eyes by the test article was observed during the entire reading period. Red remnants of the test article in eye or conjunctival sac were observed at the 1-h reading. No corrosion was observed at any of the measuring intervals. In conclusion, FAT 93503/A is considered to be "not irritating" to the rabbit eye.