Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
July 1994
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Protocol study under GLP, no significant deviations

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report Date:
1994

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)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Contains more impurities than submission substance

Sponsor's identification : GBS-5
Batch number : GLS 30P (see CoA in the report attached)
Date received : 23 June 1994
Description : wh i te powder
Storage conditions : room temperature over silica gel

Composition according to Certificate of Analysis
Glutamic acid - N,N-diacetic acid, tetrasodium salt 70.70%

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 weeks
- Weight at study initiation: 2.76 - 2.96 kg
- Housing:individually housed in suspended metal cages.
- Diet (e.g. ad libitum): ad libitium
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days minimum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-22
- Humidity (%): 65 -83 (occasionally above protocl limit of 70%; irrelevant)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 25 July 1994 To: 29 July 1994.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
approx. 0.1 ml, i.e approx 31 mg
Duration of treatment / exposure:
single installation, no irrigation to remove reported substance
Observation period (in vivo):
72 hrs
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE:
no removal

The second and third animal received one drop of local anaesthetic 1-2 min before treatment.

SCORING SYSTEM:
DRAIZE SCALE FOR SCORING OCULAR IRRITATION
1. CONJUNCTIVAE
(A) Redness (refers to palpebral and bulbar conjunctivae excluding cornea and iris)
Vessels normal 0
Vessels definitely injected above normal 1
More diffuse, deeper crimson red, indiviual vessels not easily discernible 2
Diffuse beefy red 3
(B) Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids half closed to completely closed 4
(C) Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids 2
Discharge uith moistening of the lids and hairs a considerabte area around the eye 3
THE TOTAL SCORE (A + B + C) x 2, MAXIMUM TOTAL = 20
2. IRIS
(D) Values
Normal 0
Folds above normal, congestion, swelling, circumcorneal injection
(any or all of these or combination of any thereof), iris still still reacting to light
(sluggish reaction is positive) 1
No reaction to light, haemorrhage, gross destruction (any or all of these) 2
THE TOTAL SCORE = D x 5, MAXIMUM TOTAL = 10
3. CORNEA
(E) Degree of Opacity (most dense area used)
No opacity 0
Scattered or diffuse areas, details of iris clearly visible 1
Easily discernible translucent areas, details of iris slightly obscured 2
Opalescent areas, no details of iris visible, size of pupil barely discernible 3
Opaque, iris invisible 4
(F) Area of Cornea involved
One quarter (or less) but not zero 1
Greater than one quarter but less than half 2
Greater than half but less than three quarters 3
Greater than three quarters, up to whole area 4
THE TOTAL SCORE = (E x F) x 5, MAXIMUM TOTAL = 80
MAXIMUM TOTAL SCORE POSSIBLE = 110

TOOL USED TO ASSESS SCORE: hand-slit lamp

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0.11
Max. score:
3
Reversibility:
fully reversible within: 2 days
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24/48/72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
No corneal or iridial effects were noted during the study.
Minimal conjunctival irritation was noted in all treated eyes one hour after treatment and persisted in one treated eye at the 24-hour observation.
All treated eyes appeared normal 48 hours after treatment.

Any other information on results incl. tables

INDIVIDUAL & MEAN SCORES FOR CORNEA, IRIS & CONJUNCTIVAE REQUIRED FOR EC LABELLING REGULATIONS

Rabbit Number &Sex (Bodyweight kg)

Time After Treatment (hrs)

Corneal Opacity

Iridial Inflammation

Conjunctival Redness

Conjunctival Chemosis

39 female (2.90)

24

0

0

1

0

48

0

0

0

0

72

0

0

0

0

Total

0

0

1

0

Mean

0

0

0.33

0

15 female (2.76)

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

Total

0

0

0

0

Mean

0

0

0

0

26 Male (2.96)

24

0

0

0

0

48

0

0

0

0

72

0

0

0

0

0

0

Total

0

0

0

0

Mean

0

0

0

0

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test material, GBS-5, did not produce positive criteria in any rabbit according to the OECD-GHS labelling regulations. No symbol and risk phrase are therefore required.
Executive summary:

A study was performed to assess the irritancy potential of the test material, GBS-5, to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 February 1987) and Method B5 in Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single application of the test material to the non-irrigated eye of three rabbits produced minimal conjunctival irritation. All treated eyes appeared normal 48 hours after treatment. The test material did not meet the criteria for classification as irritant according to OECD-GHS labelling regulations. No symbol and risk phrase are required.