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

Endpoint summary

Description of key information

Disperse Red 302:1 is not an irritant to skin and eyes of rabbits.

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:

25 January, 2000 to 3 February, 2000.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: New Zealand White Rabbit, SPF.
- Age at study initiation: 16 weeks (male), 14 weeks (females).
- Weight at study initiation: 2.8-3.1 kg.
- Accommodation: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood and hay sticks for gnawing.
- Identification: By unique cage number and corresponding ear number.
- Diet: ad libitum
- Water: Tap water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 35-54 %
- Air changes: 10-15 air changes per hour.
- Photoperiod: light cycle of 12 hours light and 12 hours dark.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

other: Bi-distilled water.

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount: 0.5 g/animal

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

1 male and 2 females

Details on study design:

TEST SITE
- Area of exposure: Left flank of the rabbit.
- % coverage: 6 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Skin was flushed with lukewarm tap water to clean the application site.
- Time after start of exposure:

SCORING SYSTEM (Grading of Skin Reactions):
ERYTHEMA AND ESCHAR FORMATION:
-No erythema: 0
-Very slight erythema: 1
-Well-defined erythema: 2
-Moderate to severe erythema: 3
-Severe erythema (beet redness) or eschar formation (injuries in depth preventing erythema) reading:4

OEDEMA FORMATION:
-No oedema: 0
-Very slight oedema (barely perceptible): 1
-Slight oedema (edges of area well-defined by definite raising): 2
-Moderate oedema (edges raised approximately 1 mm): 3
-Severe oedema (raised more than 1 mm and extending beyond the area of exposure: 4

Irritation parameter:

erythema score

Basis:

mean

Remarks:

1 male and 2 females

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Remarks:

1 male and 2 females

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Application of the test article to healthy intact rabbit skin resulted in a primary irritation score of 0.00.
Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 oedema. No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin.

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 staining to light red staining produced by the test article was observed on the treated skin of all animals during all examination periods.

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

None

Interpretation of results:

GHS criteria not met

Conclusions:

FAT 93504/A is considered to be "not irritating" to rabbit skin.

Executive summary:

The primary skin irritation potential of FAT 93504/A was determined according to the OECD Guideline 404 (Acute Dermal Irritation/Corrosion). The primary skin irritation was investigated by topical application of 0.5 g to 6 cm2 intact left flank of each of three, (1male and 2 females), young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours, after removal of the dressing. The scores of each animal at the following reading times (24, 48, 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 by the number of data points. The primary irritation score was 0.00 (max. 8.0). Local signs (mean values from 24 to 72 hours) consisted of grade 0.00 erythema and grade 0.00 oedema. The test article caused red staining or light red staining of the treated skin during all examination periods. No corrosive effects were noted on the treated skin of any animal at any measuring interval. Based upon the referred classification criteria (EEC Commission Directive 93/21/EEC of April 27, 1993), the test article is considered to be "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

Study period:

22 February, 2000 to 3 March, 2000.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

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.

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

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 72 hours

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.

None

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The primary skin and eye irritation studies were carried out according to the OECD Guideline 404 (Acute Dermal Irritation/Corrosion) and OECD Guideline 405 (Acute Eye Irritation/Corrosion respectively. No signs of either skin or eye irritation/corrosion were noted in animals at any of the measuring intervals. Based upon the referred classification criteria (EEC Commission Directive 93/21/EEC of April 27, 1993), the test article is considered to be "not irritating" to rabbit skin and eye.

Justification for classification or non-classification

Based upon the available data, Disperse Red 302:1 is considered to be "not irritating" to rabbit skin and eye. Therefore, no classification is warranted according to criteria set out by Regulation (EC) No. 1272/2008 (CLP).