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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 July 1996 - 12 July 1996
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2,2'-AZOBIS(ISOBUTYRONITRILE) (AZDN)
- Molecular weight (if other than submission substance): 164.24
- Physical state: Solid (white powder)
- Analytical purity: 99.2 %
- Purity test date: 27.03.0995
- Lot/batch No.: 721
- Expiration date of the lot/batch: April 1997
- Storage condition of test material: In dark, at room temperature and at +4 °C from June 1996

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Elevage cunicole de Val de Selle, 80160 Prouzel, FRANCE
- Weight at study initiation: 2.8 +/- 0.1 kg
- Age at study initiation : no data
- Housing: no data
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days before the beginning of the study


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 +/- 3 °C
- Humidity (%): 30 -70 %
- Air changes (per hr): 12 cycles/hour
- Photoperiod (hrs dark / hrs light): 12h/12h


Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the right eye which remained untreated served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 mg
Duration of treatment / exposure:
The lower and upper eyelids were held together for about one second to avoid any loss of test substance. The eyes were not rinsed after administration of the test substance.
Observation period (in vivo):
The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test substance. If there was persistent ocular irritation after 72 hours, the observation period is extended to a maximum of 21 days (until day 22) in order to determine the progress of the lesions and their reversibility.
Number of animals or in vitro replicates:
Three rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eyes were not rinsed after administration of the test substance.

SCORING SYSTEM: Ocular irritation was evaluated for each animal according to the grading scale of OECD test guideline 405


TOOL USED TO ASSESS SCORE: To determine the presence or absence of corneal opacification, one or two drops of 0.5 % sodium fluorescein solution was instilled into the eye before the 24-hour reading.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 24-72 hours
Irritation parameter:
conjunctivae score
Remarks:
(Redness)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24, 48 and 72 hours
Score:
0.6
Max. score:
3
Reversibility:
fully reversible within: 48-72 hours
Irritation parameter:
iris score
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24, 48 and 72 hours
Score:
0.1
Max. score:
2
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: (1 animal)
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24, 48 and 72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48-72 hours
Irritation parameter:
cornea opacity score
Remarks:
(area)
Basis:
mean
Remarks:
3 rabbits
Time point:
other: 24-48-72 hours
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48-72 hours
Irritant / corrosive response data:
At the 1-hour reading, slight conjunctival reactions were observed in all animals: very slight or slight chemosis (grade 1 or 2) and very slight conjunctival redness (grade 1) were noted. These conjunctival reactions persisted up to day 2 (1 animal) and 3 (2 animals).
A very slight iritis (grade 1) was observed in one animal on day 1: it persisted for 24 hours.
At the 24-hour reading, a very slight corneal opacity (grade 1) was observed in two animals: it persisted for 24 hours in one of them.
The mean scores calculated for each animal over 24, 48 and 72 hours were 0.3, 0.0 and 1 for chemosis; 0.3, 0.7 and 0.7 for redness of the conjunctiva; 0.0, 0.0 and 0.3 for iris lesions and 0.3, 0.0 and 0.7 for corneal opacity.

Any other information on results incl. tables

Individual ocular examination and mean values of the scores recorded at each reading (24, 48 and 72 hours) for each animal :

Rabbit number

Region of eye

Description

of ocular reactions

Scores

Mean irritation score

1h

D1

24h

D2

48h

D3

72h

D4

01

Conjunctivae

 

 

Iris

 

Corneal opacity

- Chemosis

- Redness

 

 

 

- Intensity

 

2

1

 

0

 

0

 

1

1

 

0

 

1

 

0

0

 

0

 

0

 

0

0

 

0

 

0

 

0.3

0.3

 

0

 

0.3

 

02

Conjunctivae

 

 

Iris

 

Corneal opacity

- Chemosis

- Redness

 

 

 

- Intensity

1

1

 

0

 

0

 

0

1

 

0

 

0

 

0

1

 

0

 

0

 

0

0

 

0

 

0

 

0

0.7

 

0

 

0

 

03

Conjunctivae

 

 

Iris

 

Corneal opacity

- Chemosis

- Redness

 

 

 

- Intensity

2

1

 

1

 

0

 

2

1

 

1

 

1

 

1

1

 

0

 

1

 

0

0

 

0

 

0

 

1

0.7

 

0.3

 

0.7

 

Applicant's summary and conclusion

Interpretation of results:
slightly irritating
Remarks:
Migrated information (but not classified) Criteria used for interpretation of results: other: According to EU regulation (EC) No 1272/2008 (CLP) and EU Directive 67/584/EEC
Conclusions:
Very slight and transient ocular reactions were observed after administration of the test item into the eye of 3 rabbits. According to the criteria laid down in Council Directive 67/548/EEC, AZDN is considered as non-irritant for the eye.
Executive summary:

The potential of the test item 2,2'-AZOBIS(ISOBUTYRONITRILE) to induce eye irritation was evaluated in rabbits according to OECD guideline 405. The study was conducted in compliance with the principles of the Good Laboratory Practice Regulations.

Methods:

As no irritant effects were anticipated, a single dose of 100 mg of the test substance was introduced into the left conjunctival sac of three New Zealand White rabbits. The right eye served as a control. The test substance was used in its original form. The eyes were not rinsed after administration of the test substance.

The mean values of the scores recorded for each animal after 24, 48 and 72 hours were calculated.

Results:

At the 1-hour reading, slight conjunctival reactions were observed in all animals: very slight or slight chemosis (grade 1 or 2) and very slight conjunctival redness (grade 1) were noted. These conjunctival reactions persisted up to day 2 (1 animal) and 3 (2 animals).

A very slight iritis (grade 1) was observed in one animal on day 1: it persisted for 24 hours. At the 24-hour reading, a very slight corneal opacity (grade 1) was observed in two animals: it persisted for 24 hours in one of them.

The mean scores calculated for each animal over 24, 48 and 72 hours were 0.3, 0 and 1 for chemosis, 0.3, 0.7 and 0.7 for redness of the conjunctivae, 0, 0 and 0.3 for iris lesions and 0.3, 0 and 0.7 for corneal opacity.

Conclusions:

According to the criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item 2,2'-AZOBIS(ISOBUTYRONITRILE) is considered as non-irritant for the eye and is not classified.