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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:
From February 11, 2008 to May 07, 2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Principles of method if other than guideline:
- Japanese Ministry of Agriculture, Forestry and Fisheries
(JMAFF), 12 Nousan, Notification No 8147, November 2000,
including the most recent partial revisions.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Nature of substance: powder

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
- Source: Harlan, Horst, The Netherlands
- Age at study initiation: at least 6weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually in labeled cages with perforated floors
- Water: ad libitum
- Acclimation period: at least 5 days
- Temperature (°C): 21.0 ± 3.0 °C
- Humidity (%): 30-70%
- Photoperiod: 12-hrs dark / 12-hrs light

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
- Amount(s) applied (volume or weight with unit): 58.6 mg
Observation period (in vivo):
1, 24, 48, 72 hours and 7 days
Number of animals or in vitro replicates:
Three

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal: 743, 747 and 748
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal: 743, 747 and 748
Time point:
24/48/72 h
Score:
0
Max. score:
0
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal: 743 and 748
Time point:
24/48/72 h
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Remarks:
Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24 and 48 hours after dosing.
Irritation parameter:
conjunctivae score
Basis:
animal: 747
Time point:
24/48/72 h
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24, 48 and 72 hours after dosing.
Irritation parameter:
chemosis score
Basis:
animal: 743, 747 and 748
Time point:
24/48/72 h
Score:
0.4
Max. score:
1
Reversibility:
fully reversible within: 7 days
Remarks on result:
probability of weak irritation
Irritant / corrosive response data:
Reversibility of any observed effect: Changes fully reversible within 7 days
Other effects:
Red/purple staining of (peri) ocular tissues by the test
substance was observed during the observation period. This
staining hampered scoring of erythema at 1, 24, 48 and/or 72
hours after dosing. No test substance remnants were seen.

Red/purple staining of the fur on the head and paws, caused
by the test substance, was noted during the observation
period.

Any other information on results incl. tables

Table 1. Individual eye irritation scores 

Animal

Time after dosing

Cornea

Iris

Conjunctivae

Comments

Opacity

(0-4)

Area

(0-4)

Flour area

(%)2

(0-2)

Redness

(0-3)

Chemosis

(0-4)

Discharge

(0-3)

7431

1 hour

0

0

0

0

2

1

e a

24hours

0

0

0

1

1

e a

48 hours

0

0

0

0

0

e a

72 hours

0

0

0

1

0

0

e a1

7 days

0

0

0

0

0

0

e a1

747

1 hour

0

0

0

0

2

1

e a

24 hours

0

0

0

1

1

e a

48 hours

0

0

0

0

1

e a

72 hours

0

0

0

0

0

e a

7 days

0

0

0

0

0

0

e a1

748

1 hour

0

0

0

0

2

1

e a

24 hours

0

0

0

1

1

e a

48 hours

0

0

0

1

1

e a

72 hours

0

0

0

1

0

1

e a1

7 days

0

0

0

0

0

0

e a1

1Sentinel

2Green staining after fluorescein treatment (percentage of total corneal area)

 

Comments:

a   Red/purple staining of the eye lids, nictitating membrane and sclera, which hampered scoring of erythema.

a1  Red/purple staining of the eye lids, nictitating membrane and sclera, which did not hamper scoring of erythema.

e   Red/purple staining of the head and paws by the test substance.

Table 2. Mean value eye irritation scores

Animal

Mean 24, 48 and 72 hours

Corneal opacity

Iris

Conjunctive

Redness

Chemosis

743

0.0

0.0

b

0.3

747

0.0

0.0

c

0.3

748

0.0

0.0

b

0.7

Comments:

b  Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24 and 48 hours after dosing. Erythema grade 1 was observed at 72 hours after dosing.

c  Red/purple staining of the eye lids, nictitating membrane and sclera hampered scoring of erythema at 1, 24, 48 and 72 hours after dosing.

Table 3. Animal specifications

Animal

Sex

Age at start (weeks)

Body weight (grams)

prior to application

at termination

743

7-9

1249

1402

747

9

1625

1792

748

9

1525

1751

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
According to OECD 405, EU Method B.5, EPA OPPTS 870.2400 and JMAFF test method, Everzol Red CDN Crude showed that non-irritant to the eye. Therefore, Everzol Red CDN was not met a category based on GHS criteria.
Executive summary:

This test using the procedures outlined in the NOTOX Study Plan for 487478. There were no test article effects on body weight. Everzol Red CDN Crudewas given by a single ocular application at 58.6 mg amount to NZW rabbits and followed by ocular examination within 7 days. Three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and discharge. The observed irritation had completely resolved within 72 hours in one animal and within 7 days in two animals. No iridial irritation or corneal opacity was observed. On the basis of the test results given above, the response of the test article was not any irritant to the eye.