Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 Jun - 25 Jul 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study. No topical anaesthetics or systemic analgesics were used.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted Oct 2012
Deviations:
yes
Remarks:
no topical anaesthetics or systemic analgesics were used
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries, 12 Nousan, Notification No. 8147, November 2000, including the most recent partial revisions
Deviations:
no
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): PM-5927
- Physical state: off-white powder
- Lot/batch No.: 07-02
- Expiration date of the lot/batch: 05 Feb 2008
- Storage condition of test material: at room temperature in the dark
- Other: pH (1% in water, indicative range) 5.2 - 6.0

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, the Netherlands
- Age at study initiation: 9 - 11 weeks
- Weight at study initiation: 1821 - 2301 g (range)
- Housing: animals were housed individually in cages with perforated floors (56 x 44 x 37.5 cm, Scanbur, Denmark)
- Diet: pelleted diet for rabbits, K-H (SSNIFF Spezialdiäten GmbH, Soest, Germany), approximately 100 g/day. Hay (TechniLab-BMI BV, Someren, the Netherlands) was provided at least 3 times/week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 - 24.1 (actual range)
- Humidity (%):43 - 80 (actual range)
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL, equivalent to on average 64.2 mg
Duration of treatment / exposure:
Single application without washing
Observation period (in vivo):
7 days
Reading time points: 1, 24, 48 and 72 h and 7 days
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the eye remained unwashed after installation

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: a solution of 2% fluorescein in water (adjusted to pH 7) was instilled into both eyes of each animal to quantitatively determine the corneal epithelial damage

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility: not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
of 3 animals
Time point:
other: mean after 24/48/72 h
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: mean after 24/48/72 h
Score:
2.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: mean after 24/48/72 h
Score:
2.33
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: mean after 24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean after 24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean after 24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean after 24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
One hour after instillation, 3/3 rabbits had slight or moderate conjunctivae (score 1 or 2) and slight chemosis (score 1) (see Table 1 under 'Any other information on results incl. tables').
At the 24- and 48-hour reading time point moderate to severe conjunctivae was noted in 3/3 animals; which persisted as slight to moderate conjunctivae until 72 hours after installation. Slight-moderate chemosis was observed in 3/3 rabbits 24 and 48 hours after installation, and in 2/3 until the 72-hour reading time point. Iritis (score 1) was observed in 3/3 rabbits until 24 hours after installation. All eye irritation effects had cleared within the 7-day reading time point. No irritation reactions were observed in the cornea.
Other effects:
There was no mortality. No clinical signs were observed and the body weight increase was normal for this species and strain.

Any other information on results incl. tables

 

Table 1. Individual eye irritation scores

Rabbit #

 

Time

 

Conjunctivae/

redness

Chemosis

 

Iris

 

Cornea

 

1

 

 

 

 

1 h

1

1

1

0

24 h

3

2

1

0

48 h

3

1

0

0

72 h

7 d

2

0

0

0

0

0

0

0

Average*

2.67

1.0

0.33

0.0

2

 

 

 

 

1 h

1

1

1

0

24 h

3

2

1

0

48 h

2

1

0

0

72 h

7 d

2

0

1

0

0

0

0

0

Average*

2.33

1.33

0.33

0.0

3

 

 

 

 

1 h

2

1

1

0

24 h

2

1

1

0

48 h

2

1

0

0

72 h

7 d

1

0

1

0

0

0

0

0

Average*

1.67

1.0

0.33

0.0

 

 

Applicant's summary and conclusion

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: Eye irrit 2, H319