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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

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 phenyl carbonate

EC Number:

248-882-8

EC Name:

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

Cas Number:

28173-59-3

Molecular formula:

C23H17NO7

IUPAC Name:

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

Test material form:

not specified

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Tet 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 14-15 weeks (females)
- Weight at study initiation: 2.6 - 3.2 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with autoclaved wood (RCC Ltd, Füllinsdorf) and haysticks for gnawing.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum.
- 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 %
- Photoperiod: light cycle of 12 hours light and 12 hours 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 93504/A was weighed and applied undiluted as it was delivered by the sponsor.

Duration of treatment / exposure:

Single application

Observation period (in vivo):

72 hours

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:
- Opacity: degree of density (area most dense taken for reading).
- 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, hemorrhage, 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

Time point:

24/48/72 h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritant / corrosive response data:

IRRITATION:
The primary irritation score was calculated by totaling the individual cumulative scores at 24, 48 and 72 hours and then dividing the resulting total by the number of data points. The primary irritation score was 0.22 (max. 13).

The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 corneal opacity, grade 0.00 iris, grade 0.22 redness of the conjunctivae and grade 0.00 Chemosis of the conjunctivae.

Slight corneal opacity was seen in one animal at the 1-hour examination. Hyperemic conjunctival blood vessels were noted in all animals at the 1-hour examination and persisted in one animal through 48 hours. Slight conjunctival swelling and a slightly reddened sclera were also seen in all animals one hour after the treatment. All eye reactions were clear within 72 hours after treatment.

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

Other effects:

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

COLORATION
Red staining of the test article in eye or conjunctival sac were observed in all animals through the whole reading period (marked staining at the 1-hour examination) but did not influence the reaction reading. Red remnants of the test article in eye or conjunctival sac were observed in all animals at the 1-hour reading and still persisted in one animal at the 24-hour examination.

BODY WEIGHTS
The body weight of all rabbits were considered to be within the normal range of variability.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 93504/A is considered to be not irritating to the rabbit eyes.

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. This study was done according to the OECD Guideline 405 (Acute Eye Irritation / Corrosion). The primary eye irritation potential was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits (1 male and 2 females). The treated eyes were not rinsed after application.The untreated eye were used as control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test article application. The scores of each animal at the following reading times (24, 48 and 72 hours) 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 hours and then dividing the resulting total by the number of data points. The primary irritation score was 0.22 (max. 13). The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 corneal opacity, grade 0.00 iris, grade 0.22 redness of the conjunctivae and grade 0.00 Chemosis of the conjunctivae. Slight corneal opacity was seen in one animal at the 1-hour examination. Hyperemic conjunctival blood vessels were noted in all animals at the 1-hour examination and persisted in one animal through 48 hours. Slight conjunctival swelling and a slightly reddened sclera were also seen in all animals one hour after the treatment. All eye reactions were clear within 72 hours after treatment. Red staining of the test article in eye or conjunctival sac were observed in all animals through the whole reading period (marked staining at the 1-hour examination) but did not influence the reaction reading. Red remnants of the test article in eye or conjunctival sac were observed in all animals at the 1-hour reading and still persisted in one animal at the 24-hour examination. No corrosion was observed at any of the time intervals. In conclusion, FAT 93504/A is considered to be not irritating to the rabbit eyes.