Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed under GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
inspected November 1998; signature: March 1999

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
gas under pressure: refrigerated liquefied gas
Details on test material:
- Physical state: liquid
- Stability under test conditions: Stable under storage conditions.
- Storage condition of test material: In the original container, in the refrigerator (range of 4 ± 3 °C), away from direct sunlight.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Recognised animal supplier
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 3.0 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with autoclaved wood and haysticks for gnawing.
- Diet (e.g. ad libitum): certified pelleted diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.5-23.5
- Humidity (%): 49-71
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 h dark / 12 h light

IN-LIFE DATES: From: 17/08/2000 To: 31/08/2000

Test system

Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
Treated eyes were not rinsed after instillation. Occular reaction was assessed at 1, 24, 48 and 72 hours, as well as 7 days after application.
Observation period (in vivo):
Occular reaction was assessed at 1, 24, 48 and 72 hours, as well as 7 days after application.
Number of animals or in vitro replicates:
3 (1 male; 2 females)
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): none
- Time after start of exposure: not applicable

SCORING SYSTEM: The ocular reaction was assessed according to the numerical scoring system listed in the EEC Commission Directive 92/69/EEC, July 31, 1992 at approximately 1, 24, 48 and 72 hours, as well as 7 days after application.

CORNEA
Opacity: degree of density (area most dense taken for reading)
No ulceration or opacity ........................................................................................................ 0
Scattered or diffuse areas of opacity (other than slight dulling of normal luster),
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

IRIS
Normal ...................................................................................................................................... 0
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or
injection, any of these or combination 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

CONJUNCTIVAE
Redness (refers to most severe reading of palpebral and bulbar conjunctivae when compared with
control eye)
Blood vessels normal ............................................................................................................... 0
Some blood vessels definitely hyperemic (injected) ........................................................... 1
Diffuse, crimson color, individual vessels not easily discernible ..................................... 2
Diffuse beefy red ...................................................................................................................... 3

Chemosis: lids and/or nictitating membranes
No swelling .................................................................................................................................. 0
Any swelling above normal (including nictitating membranes) .......................................... 1
Obvious swelling with partial eversion of lids ....................................................................... 2
Swelling with lids about half-closed ........................................................................................ 3
Swelling with lids more than half-closed ................................................................................ 4

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
1.67
Max. score:
13
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
0.67
Max. score:
13
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
0.33
Max. score:
13
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
13
Reversibility:
fully reversible
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
13
Reversibility:
fully reversible
Irritant / corrosive response data:
No corneal or iridal effect was observed in the treated eyes of all animals. Some definitely hyperemic blood vessels of the conjunctivae/nictitating membrane were noted in all animals at the 1-hour reading before diminishing to be clear at 24 (one animal), 48 (one animal) or 72 hours (one animal). Slight swelling of the conjunctivae/nictitating membrane was seen in two animals at the 1-hour reading.
Other effects:
Slight redness of the sclera was observed in two animals at the 1-hour reading and persisted in one animal through 24 hours. Slight watery discharge was noted in one animal at the 1-hour reading. All eye reactions were clear within 72 hours after treatment.

Any other information on results incl. tables

Table 1. Individual eye irritation scores

Animal Evaluation interval Corneal Opacity Iris Conjunctivae Cumulative Sclera
Redness Chemosis Score Mean
1 1 hour 0 0 1 1 2 1.67 1
2 0 0 1 1 2 1
3 0 0 1 0 1 0
1 24 hours 0 0 0 0 0 0.67 0
2 0 0 1 0 1 1
3 0 0 1 0 1 0
1 48 hours 0 0 0 0 0 0.33 0
2 0 0 1 0 1 0
3 0 0 0 0 1 0
1 72 hours 0 0 0 0 0 0 0
2 0 0 0 0 0 0
3 0 0 0 0 0 0
1 7 days 0 0 0 0 0 0 0
2 0 0 0 0 0 0
3 0 0 0 0 0 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 this study the test material is not considered to be irritating to the eye.
Executive summary:

The study was performed to the requirements of OECD 405 and EU Method B.5 in accordance with GLP to assess the irritancy potential of the test material to the eye following a single application in the New Zealand White rabbit. A volume of 0.1 ml of the test material was placed into the conjunctival sac of the left eye of all test animals. The right eye remained untreated and was used for control purposes. The treated eyes were not rinsed after instillation. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48,72 hours and 7 days following treatment. No corneal or iridal effect was observed in the treated eyes of all animals. Some definitely hyperemic blood vessels of the conjunctivae/nictitating membrane were noted in all animals at the 1-hour reading before diminishing to be clear at 24 (one animal), 48 (one animal) or 72 hours (one animal). Slight swelling of the conjunctivae/nictitating membrane was seen in two animals at the 1-hour reading. All treated eyes appeared normal at the 72h observation. Under the conditions of this study the test material is not considered to be irritating to the eye.