Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 May 1984 - 5 May 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Reliability 2 is assigned because the study was conducted according to an acceptable method comparable to OECD TG 405 and in compliance with GLP, but with minor deviations that do not influence the test results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1984
Report Date:
1984

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(number of animals used, lack of extended observation period, slight differences in grading system which do not influence the relevance of the results)
Qualifier:
according to
Guideline:
other: Federal Register 1973, Volume 38, No. 187, 1500.42
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Storage condition of test material: in a brown glass screw-top bottle at ambient temperature

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leics.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.21-2.53 kg
- Housing: individually, in suspended metal cages
- Diet (e.g. ad libitum): standard laboratory diet (Rabbit Diet, A.W. Tindall Limited), ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: minimum five days prior to start of study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 3°C
- Humidity (%): 61-65 %
- Air changes (per hr): approximately 10
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: contralateral eye of test animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM:
Assessment of damage/irritation was made at 24, 48 and 72 hours following treatment according to the numerical evaluation according to Draize J.H. 1959, Assoc. of Food and Drug Officials of the USA, Austin, Texas, "The appraisal of the Safety of Chemical in Foods, Drugs and Cosmetics"). Readings were performed at 24, 48 and 72 48 hours after instillation.

TOOL USED TO ASSESS SCORE:
Examination was done by the use of a standard opthalmoscope (Keeler). Observation of corneal opacity was carried out under ultra-violet illumination (Mineralight UVSL-58) preceded by the instillation into the eye or fluorescein B.P.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal: #1, #2, #3, #4 and #5
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
(opacity)
Basis:
animal #6
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
0.33
Max. score:
4
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #4 and #5
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
0.67
Max. score:
2
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #4
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #1 and #6
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal: #2, #3 and #5
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
1
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal: #2, #3 and #4
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
other: 24, 48 and 72 hrs (mean)
Score:
2
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Irritant / corrosive response data:
The test material produced minimal or slight ocular irritation in 6 out of 6 animals.
- Cornea: diffuse opacity was observed in one rabbit, dulling of the normal lustre of the cornea was seen in two other rabbits (24 hours reading). Dulling was still apparent in one rabbit after 48 hours and 72 hours reading.
- Iris: iritis was observed in one rabbit at 24 and 48 hours reading only.
- Conjunctivae/chemosis: diffuse, crimson-red colouration including slight/distinct swelling of eyelids was observed in 3 rabbits at 24 hours reading. Mild reactions were seen in other 3 animals. At 48 hours, mild inflammation with or without distinct swelling and partial eversion of the eyelid was observed in all animals. This persisted in 4 animals up until the 72 hours reading.
Despite slight irritation at the end of the 72h observation period it is anticipated that the irritation will be resolved within 14 days because of the slight nature of the effect.

Any other information on results incl. tables

Individual scores and individual general totals for ocular irritation:

Rabbit number

1 (619)

2 (413)

3 (419)

4 (427)

5 (429)

6 (431)

Hours after treatment

24

48

72

24

48

72

24

48

72

24

48

72

24

48

72

24

48

72

Cornea

 

E = Degree of opacity

0

0

0

D

0

0

D

0

0

0

0

0

0

0

0

1*

D

D

F = Area of opacity

0

0

0

4

0

0

4

0

0

0

0

0

0

0

0

1

1

1

Score (ExF)x5

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

0

0

Iris

 

D

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

1*

1*

0

Score (Dx5)

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

5

5

0

Conjunctivea

 

A = Redness

2*

1

1

2*

1

0

1

1

1

1

1

0

1

1

1

2*

1

1

B = Chemosis

2*

1

1

1

1

0

1

1

0

1

1

0

0

0

0

2*

2*

2*

C = Discharge

1

0

0

1

0

0

1

0

0

1

0

0

0

0

0

3

1

0

Score (A+B+C)x2

10

4

4

8

4

0

6

4

2

6

4

0

2

2

2

14

8

6

Individual general totals

10

4

4

8

4

0

6

4

2

6

4

0

2

2

2

24

13

6

 

GT1

GT2

GT3

GT1

GT2

GT3

GT1

GT2

GT3

GT1

GT2

GT3

GT1

GT2

GT3

GT1

GT2

GT3

* = Positive reaction

D – Dulling of the cornea

Based on the classification systems as included in the study report, the classification of the substance is as follows:

- Classification according to Federal Register 1973:

3/6 rabbits showed positive ocular reactions and the test material therefore gave an INCONCLUSIVE result according to the Federal Register.

 

- E.T.A.D. Classification (Scoring system based on Draize 1959):

The test material produced a Group Mean 3 -Day Score of 5.6 and was therefore classified as NON-IRRITANT to the eye according to ETAD.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an eye irritation study with rabbits, performed according to a method similar to OECD TG 405, the corneal opacity and/or iritis score were not ≥1 and/or the conjunctival redness and/or oedema (chemosis) score were not ≥2. Based on these results, the substance does not need to be regarded as an eye irritant.
Executive summary:

The potential of Floral Super to cause eye irritation was determined in a test according to a method similar to OECD guideline 405. Six New Zealand White female rabbits were exposed to 0.1 ml of the undiluted test article in one of the eyes. The other eye served as a control. The eyes were examined and the changes graded according to a numerical scale 24, 48 and 72 hours after dosing.

The test material produced minimal or slight ocular irritation in 6 out of 6 rabbits. The corneal opacity and/or iritis score were not ≥1 and/or the conjunctival redness and/or oedema (chemosis) score were not ≥2. Reversibility of the effect within 14 days can be anticipated. Based on these results, the substance does not need to be regarded as an eye irritant.