Butyl 2-[[3-[[(2,3-dihydro-2-oxo-1H-benzimidazol-5-yl)amino]carbonyl]-2-hydroxy-1-naphthyl]azo]benzoate

Endpoint summary

Description of key information

PR208

The skin irritating potential of the test item was assessed according to OECD TG 404 and GLP conditions. The test item did not reveal any irritation potential on the skin of rabbits.

The test item did not induce significant or irreversible damage to the rabbit eye in this study according to OECD test guideline no. 405 and GLP conditions.

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:

AUG 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 404), performed under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratoires France, L'Arbresle, France
- Age at study initiation: 12 weeks (male), 14 weeks (females)
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 85/05; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g/animal
VEHICLE
- Amount applied: 0.5 mL/animal

Duration of treatment / exposure:

4 h

Observation period:

14 days

Number of animals:

3 (1 male, 2 females)

Details on study design:

TEST SITE
- Area of exposure: 4 cm x 4 cm

REMOVAL OF TEST SUBSTANCE
- Washing (if done): flushed with lukewarm tap water
- Time after start of exposure: 4 h

SCORING SYSTEM:
Grading of Skin Reactions according to COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004
ERYTHEMA AND ESCHAR FORMATION
No erythema..................................................................................................................................0
Very slight erythema....................................................................................................................1
Well-defined erythema.................................................................................................................2
Moderate to severe erythema.....................................................................................................3
Severe erythema (beef 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:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: No edema

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: No edema

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: No erythema

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: No erythema

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: No erythema

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not applicable since no effect

Irritant / corrosive response data:

Signs such as erythema could not be evaluated in all animals one hour after treatment due to presence of staining at the application site. No erythema was detectable at any later time point (score 0) and no edema were seen at any timepoint (score 0).

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not reveal any irritation potential on the skin of rabbits, tested in this study according to OECD test guideline no. 404 and GLP conditions.

Executive summary:

Skin irritation potential of the test item was assessed in rabbits according to OECD TG 404. The red coloured test item caused a marked red staining at the test site of all animals at the 1-hour reading. Slight red staining persisted throughout the whole study in all animals.

Signs such as erythema could not be evaluated in all animals one hour after treatment due to presence of staining at the application site. No erythema was detectable at any later time point in any animal (score 0) and no edema were seen at any timepoint in any animal (score 0).

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:

2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD TG 405), performed under GLP

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland GmbH, Kisslegg, Germany
- Age at study initiation: 10-12 weeks
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls.
- Diet: Pelleted standard Provimi Kliba 3418 rabbit maintenance diet (batch no. 34/05; provided by Provimi Kliba AG, CH-4303 Kaiseraugst); ad libitum
- Water: Community tap water from Füllinsdorf, ad libitum
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 g

Duration of treatment / exposure:

single application, the treated eyes were not rinsed after instillation

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 (1 male, 2 females)

Details on study design:

SCORING SYSTEM:
Grading of Ocular Lesions according to COMMISSION DIRECTIVE 2004/73/EC, APRIL 29, 2004; comparable to Draize system

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

TOOL USED TO ASSESS SCORE:
Eye examinations were made with a Varta Cliptrix diagnostic-lamp (Roth AG, Reinach/Switzerland).

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not applicable since no effect

Irritation parameter:

iris score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

2

Reversibility:

other: reversibility not applicable since no effect

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: #2 and #3 each

Time point:

24/48/72 h

Score:

ca. 0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

ca. 0

Max. score:

4

Reversibility:

other: reversibility not applicable since no effect

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 0.33 and 0.33 for reddening and 0.00 for all animals for chemosis, respectively.
No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.
Slight reddening of the conjunctivae was noted in all animals from the 1- to 24-hour reading and persisted up to the 72-hour reading in one animal. Slight swelling (chemosis) of the conjunctivae was observedin one animal at the 1-hour examination.
Slight reddening of the sclerae was present in two animals one hour after treatment and persisted in one of these animals up to the 24-hour reading.
Slight ocular discharge was noted in two animals at the 1-hour reading.
No abnormal findings were observed in the treated eye of any animal 7 days after treatment.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or irreversible damage to the rabbit eye in this study according to OECD test guideline no. 405 and GLP conditions.

Executive summary:

The eye irritating potential of the test item was assessed according to OECD TG 405. Three rabbits were exposed to 0.1 mg test item. The mean score was calculated across 3 scoring times (24, 48 and72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctivae were 1.00, 0.33 and 0.33 for reddening and 0.00 for all animals for chemosis, respectively.

No abnormal findings were observed in the cornea or iris of any animal at any of the measurement intervals.

Slight reddening of the conjunctivae was noted in all animals from the 1- to 24-hour reading and persisted up to the 72-hour reading in one animal. Slight swelling (chemosis) of the conjunctivae was observedin one animal at the 1-hour examination.

Slight reddening of the sclerae was present in two animals one hour after treatment and persisted in one of these animals up to the 24-hour reading.

Slight ocular discharge was noted in two animals at the 1-hour reading.

No abnormal findings were observed in the treated eye of any animal 7 days after treatment.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

No classification, as no adverse effects were observed