Registration Dossier

Administrative data

Description of key information

GLDA-Na4 is not irritating to the rabbit skin and eye, and to the respiratory tract of rats.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin 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
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- Age at study initiation: 12-16 wks
- Weight at study initiation: 2.13 - 2.41 kg
- Housing: individually housed in suspended metal cages.
- Diet (e.g. ad libitum): at libitum
- Water (e.g. ad libitum):at libitum
- Acclimation period: 5 days minimum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 59 - 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 13 July 1994 To: 16 July 1994
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
water
Controls:
not required
Amount / concentration applied:
0.5 ml of the test material (which was found to weigh 164.3 mg), moistened with 0.5 ml of distilled water equals 328.6 g/l
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: dorsal flank, 2.5 cm x 2.5 cm
- Type of wrap if used: cotton gauze, surgical adhesive tape, tubigrip elacticated corset


REMOVAL OF TEST SUBSTANCE
- Washing (if done): swabbing with cotton gauze drenched in water
- Time after start of exposure: 4 hours


SCORING SYSTEM:
No erythema 0
Very slight erythema (barely perceptible) 1
Weil-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth) 4
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24, 48, 72 hrs
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
Very slight erythema at treated skin of 2 animals at the 1-hour observation period, all treatment sites appeared normal at the 24-hour observation
Other effects:
none
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The test material, GBS-5, produced a primary irritation index of 0.0 and was classified as a NON-IRRITANT to rabbit skin according
to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as
irritant or corrosive according to OECD-GHS labelling regulations. No symbol and risk phrase are required.
Executive summary:

A study was performed to assess the irritancy potential of the test material, GBS-5, to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 “Acute Dermal Irritation/Corrosion” (adopted 17 July 1992) and Method B4 in Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC). A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema. All treated skin sites appeared normal at the 24-hour observation. The test material produced a primary irritation index of 0.0 and was classified as a non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted. The test material did not meet the criteria for classification as irritant or corrosive according to OECD GHS labelling regulations. No symbol and risk phrase are required.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
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
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)
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.
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
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.

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

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

In two standard tests for skin and eye irritation in rabbits, GLDA-Na4 was not irritating. In the acute inhalation toxicity test in which rats were exposed to the technically highest attainable concentration, clinical signs of toxicity included slightly decreased breathing rate during exposure and sniffing in a few animals shortly after exposure up to 2 days after exposure. These signs point at very slight respiratory irritation only at a very high concentration.

Justification for selection of skin irritation / corrosion endpoint:

Well performed and reported study

Justification for selection of eye irritation endpoint:

Well performed and reported study

Justification for classification or non-classification

No classification is needed for skin and eye irritation. Based on the clinical signs observed during the acute inhalation study, it was concluded that GLDA-Na4 does not need classification for respiratory irritation.