Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11th April 2011 to 21st April 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP compliant study performed in line with appropriate guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

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 (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Physical state: off-white solid
- Storage condition of test material: room temperature in the dark
- pH: 5.0 (immediately); 4.0 (after 10 minutes); 3.9 (after 20 minutes)

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd, Leicestershire, UK
- Age at study initiation: 12 - 20 weeks
- Weight at study initiation: 2.09 - 2.48 kg
- Housing: individually in suspended cages
- Diet (e.g. ad libitum): 2930 Teklad Global rabbit diet ad libitum
- Water (e.g. ad libitum): mains water ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23ºC
- Humidity (%): 30-70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: left eye of treated animals
Amount / concentration applied:
0.1 mL of test substance
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
Two
Details on study design:
Initially, a single rabbit was treated with 0.1 mL (99.5 mg) of test material placed into the conjuctival sac of the right eye by gently pulling the lower lid away from the eyeball. The upper and lower lids were then held together for one second to prevent loss of test substance. Immediately after administration an assessment of the initial pain reaction was made. After evaluation of ocular responses in the first animal, a second animal was treated.

Assessment of ocular damage/irritation was made approximately 1, 24, 48 and 72 hours following treatment using the following Draize system:

Conjunctivae
(A) Redness
Blood vessels normal 0
Some blood vessels definitely injected 1
Diffuse, crimson read, individual vessels not easily discernible 2
Diffuse beefy red 3

(B) Chemosis
No swelling 0
Any swelling above normal 1
Obvious swelling with partial eversion of lids 2
Swelling with lids half closed 3
Swelling with lids more than half closed 4

(C) Discharge
No discharge 0
Any amount different from normal 1
Discharge with moistening of the lids and hairs adjacent to the lids 2
Discharge with moistening of the lids and hairs a considerable area around the eye 3

(D) Iris
Normal 0
Markedly deepened folds, congestion, swelling, moderate circumcorneal hyperaemia, or injection, any of these combinations of any thereof, iris still reacting to light (sluggish reaction is positive) 1
No reaction to light, hemorrhage, gross destruction (any or all of these) 2

(E) Cornea
No ulceration or opacity 0
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured 2
Nacreous area, no details of iris visible, size of pupil barely discernible 3
Opaque cornea, iris not discernible through the opacity 4

(F) Area of corneal opacity
One quarter or less but not zero 1
Greater than one quarter up to one half 2
Greater than one half up to three-quarters 3
Greater than three-quarters up to whole area 4

Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Any clinical signs of toxicity, if present were also recorded.
Individual bodyweights were recorded on Study Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 h
Score:
6
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 h
Score:
1
Max. score:
110
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
110
Reversibility:
fully reversible
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.

Minimal conjunctival irritation was noted in the treated eye of both animals at one hour after application and persisted in one animal's exposed eye at the 24 hour observation reading. Exposed eyes appeared normal at the 24 and 48 hour readings.
Other effects:
Both animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Table 1: Individual scores and individual total scores for ocular irritation

  70290 male 70323 male
 Time after treatment (h) 1 24 48 72 1 24 48 72
 Cornea (E) 0 0 0  0  0  0  0  0
 Cornea (F) 0  0  0  0  0  0  0  0
 Score (E x F) x 5 0  0  0  0  0  0  0  0
 Iris (D) 0  0  0  0  0  0  0  0
 Score (D x 5) 0  0  0  0  0  0  0  0
 Conjunctivae (redness - A) 1  0  0  0  1  1  0  0
 Conjunctivae (chemosis - B) 1  0  0  0  1  0  0  0
 Conjunctivae (discharge - C) 1  0  0  0  1  0  0  0
 Score (A + B + C) x 2 6  0  0  0  6  2  0  0
 Total score 6  0  0  0  6  2  0  0

Table 2: Individual bodyweights and bodyweight gains

 Rabbit number and sex Individual bodyweight (kg) Bodyweight gain (kg)
  Day 0 Day 3  
 70290 male 2.09 2.20 0.11
 70323 male 2.48 2.53 0.05

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 study, the test substance produced a maximum group mean score of 6.0 at the 1 hour observation reading. The substance is considered an eye irritant of minimal severity.
Executive summary:

In a GLP compliant eye irritation study conducted in line with OECD Guideline 405 and EU Method B.5, the eye irritation of the test substance was investigated. The substance produced a maximum group mean score of 6.0 at the one hour observation period and is considered an eye irritant of minimal severity. The scores suggest that the substance does require classification as an eye irritant.