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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:
10 December 2012 to 21 December 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): Bis(2-ethylhexyl) Succinate
- Storage condition of test material: In a sealed container, at room temperature, in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 13 - 14 weeks (on day 1)
- Weight at study initiation: 2.7 - 3.0 kg (on day -1)
- Housing: individually housed in cages that conformed to the 'Code of Practice for Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, UK)
- Diet: ad libitum
- Water: mains water, ad libitum
- Acclimation period: 21 - 28 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 - 22 °C
- Humidity (%): not less than 43 %
- Air changes (per hr): 15 - 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

IN-LIFE DATES: From: 10 December 2012 To: 21 December 2012

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
- Dose administration: 0.1 mL of the test material was placed into the left conjunctival sac of one rabbit, by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were then held together for a few seconds to prevent loss of the test material. The right eye remained untreated and was used for control purposes. After consideration of the ocular responses in the first treated animal, two further animals were treated.
Observation period (in vivo):
Animals were observed up to 72 hours post administration
Number of animals or in vitro replicates:
One male initially, followed by a further two males once the irritation potential was fully assessed in the first animal.
Only rabbits with eyes free from damage or irritation were accepted onto the study.
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Irrigation was not performed

SCORING SYSTEM:
The reactions observed were scored in accordance with the criteria of Draize (1977).

TOOL USED TO ASSESS SCORE:
Examination of the eye was facilitated by the use of a pencil-beam torch. Furthermore, at examinations carried out 24, 48 and 72 hours after treatment the cornea was subject to application of 1 % aqueous fluorescein solution followed by irrigation with water and illumination by an uv source. Damage to the corneal epithelium was revealed by absorption of the fluorescing dye into epithelium or stroma.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
3
Reversibility:
other: no effects observed
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
3
Reversibility:
other: no effects observed
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
3
Reversibility:
other: no effects observed
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean of 24, 48 and 72 hour time points
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritant / corrosive response data:
Scattered or diffuse areas of corneal opacity were noted in two treated eyes 24 and 48 hours after instillation. There were no irridial effects. Minimal conjunctival irritation was noted in all treated eyes 30 minutes, 1 hour and 4 hours after instillation. The eyes of all animals appeared normal by the 72 hour examination.
Other effects:
Instillation of the test material caused no initial sting response.

No observations indicative of systemic toxicity or ill health were noted for any rabbits during the course of the study.

Any other information on results incl. tables

Table 3: Individual Ocular Response

Rabbit number, sex , initial and final body weights

63 Male (2.7 - 2.7 kg)

64 Male (2.7 - 2.9 kg)

65 Male (3.0 – 3.1 kg)

Initial sting response = 0

Initial sting response = 0

Initial sting response = 0

Time after treatment

½

hr

1

hr

4

hrs

24

hrs*

48

hrs

72

hrs

½

hr

1

hr

4

hrs

24

hrs*

48

hrs*

72

hrs*

½

hr

1

hr

4

hrs

24

hrs*

48

hrs*

72

hrs*

CORNEA

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

E = Degree of Opacity

0

0

0

0

0

0

0

0

0

1

1

0

0

0

0

1

1

0

F = Area of Opacity

0

0

0

0

0

0

0

0

0

1

1

0

0

0

0

1

1

0

Score (E x F) x 5

0

0

0

0

0

0

0

0

0

5

5

0

0

0

0

5

5

0

IRIS

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

D = Reaction

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Score (D x 5)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

CONJUNCTIVAE

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A = Redness

1

1

1

0

0

0

1

1

1

0

0

0

1

1

1

0

0

0

B = Chemosis

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

C = Discharge

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Score (A + B + C) X 2

2

2

2

0

0

0

2

2

2

0

0

0

2

2

2

0

0

0

Total Score

2

2

2

0

0

0

2

2

2

5

5

0

2

2

2

5

5

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study, meaning that the test material does not require classification as an eye irritant.
Executive summary:

The eye irritation potential of the test material was determined in a GLP study which was conducted in accordance with standardised guidelines OECD 405 and EU Method B.5. Approximately 0.1 mL of test material was applied into one one of each of three rabbits and were assessed for up to 72 hours to determine the grade of ocular reaction. Instillation of the test material caused no initial sting response. Scattered or diffuse areas of corneal opacity were noted in two treated eyes 24 and 48 hours after instillation. There were no iris effects. Minimal conjunctival irritation was noted in all treated eyes 30 minutes, 1 hour and 4 hours after instillation. The eyes of all animals appeared normal by the 72 hour examination. Under the conditions of the test, the test material only elicited slight reactions in any of the animals during the course of the study that meant the test material does not require classification as an eye irritant.