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Toxicological information

Eye irritation

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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 April 2012 to 29 April 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
(the eyes of the test animals were washed 1 hour after administration of the test material).
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
yes
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
yes
GLP compliance:
yes (incl. QA statement)

Test material

Constituent 1
Chemical structure
Reference substance name:
sodium (2S)-5-oxopyrrolidine-2-carboxylate
Cas Number:
28874-51-3
Molecular formula:
C5H6NO3. Na
IUPAC Name:
sodium (2S)-5-oxopyrrolidine-2-carboxylate
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Physical state: White to pale yellow powder.
- Storage condition of test material: Controlled room temperature (15-25 °C, below 70 RH %), protected from humidity.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: Approximately 14 weeks old (adults).
- Weight at study initiation: Males ranged from 3251 to 3518 g.
- Housing: Individually in open wire cages.
- Diet: rabbit diet, ad libitum.
- Water: Municipal tap water, ad libitum.
- Acclimation period: 29 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): 15 to 20 per hour.
- Photoperiod (hrs dark / hrs light): 12 hours light per day between 06:00 and 18:00 hours.

IN-LIFE DATES: From: 26 April To: 29 April

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g.
Duration of treatment / exposure:
1 hour
Observation period (in vivo):
72 hours.
Number of animals or in vitro replicates:
Three
Details on study design:
DOSING
- Procedure: An initial test was performed using one animal to assess the initial pain reaction. After consideration of the ocular responses produced in the first animal, one hour after the treatment of the first animal, two additional animals were treated.
- Administration: The test material was instilled into the conjunctival sac of the left eye. The eyelids were held closed for a few seconds to prevent the loss of the test item.

SCORING SYSTEM
- Initial pain reaction: Immediately after the administration of the test material, an assessment of the initial pain reaction was made according to the six point scale shown in Table 1.
- Ocular response: The eyes were examined at 1, 24, 48 and 72 hours after treatment. The duration of the observation period was sufficient to identify reversibility or irreversibility of changes. The eye irritation scores were evaluated according to the scoring system by Draize (1977) shown in Table 2.

OTHER OBSERVATIONS:
- Clinical: Any clinical signs of toxicity or signs of ill-health during the study were recorded.
- Bodyweight: Individual body weight was recorded at the beginning and end of the experiment.
- Necropsy: Performed at termination of the observation period.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #1
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #2
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Remarks:
opacity
Basis:
animal #3
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
3
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0.33
Max. score:
3
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: Mean at 24, 48 and 72 hours
Score:
0
Max. score:
4
Irritant / corrosive response data:
- Initial Pain Reaction (IPR): A score of 2 was observed in all animals.
- One hour after the application: Conjunctival redness (score 1 or 2) and discharge (score 1 or 2) were seen in all rabbits. One animal showed conjuctival chemosis (score 1).
- At 24 hours after treatment: Conjunctival redness (score 1) was seen in one rabbit.
- At 48 and 72 hours after treatment: No signs of eye irritation were observed.
- Reversibility: As all signs of eye irritation had fully reversed the study was terminated after a period of 72 hours observation.
Other effects:
- Mortality: None observed during the study.
- Bodyweight: The body weight and body weight change were considered to be normal with no indication of a treatment related effect. Bodyweights ranged from 3420 to 3553 g at termination representing a weight gain of between 35 and 169 g.
- Clinical: There were no clinical signs observed that could be related to treatment.

Any other information on results incl. tables

Table 3: Individual Scores for Ocular Irritation at 1 Hour

Animal No.

Score of Irritation

IPR

Conjunctivae

Opacity of Cornea

Iris

Control Eye

Other Signs

R

CH

D

OD

OE

R

1

2

1

1

0

0

0

0

-

2

2

1

0

1

0

0

0

0

-

2

3

2

0

2

0

0

0

0

-

2

 

Table 4: Individual Scores for Ocular Irritation at 24 Hour

Animal No.

Score of Irritation

Conjunctivae

Opacity of Cornea

Iris

Control Eye

Other Signs

R

CH

D

OD

OE

R

1

0

0

0

0

0

0

0

-

2

0

0

0

0

0

0

0

-

3

1

0

0

0

0

0

0

-

 

Table 5: Individual Scores for Ocular Irritation at 48 Hour

Animal No.

Score of Irritation

Conjunctivae

Opacity of Cornea

Iris

Control Eye

Other Signs

R

CH

D

OD

OE

R

1

0

0

0

0

0

0

0

-

2

0

0

0

0

0

0

0

-

3

0

0

0

0

0

0

0

-

 

Table 6: Individual Scores for Ocular Irritation at 72 Hour

Animal No.

Score of Irritation

Conjunctivae

Opacity of Cornea

Iris

Control Eye

Other Signs

R

CH

D

OD

OE

R

1

0

0

0

0

0

0

0

-

2

0

0

0

0

0

0

0

-

3

0

0

0

0

0

0

0

-

 

R = redness, CH = chemosis; D = discharge; OD = opacity degree of density; OE = extent of opaque area; IPR = initial pain reaction.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the test, the test material was determined to be non-irritating. Slight conjunctival redness and discharge were observed in all three animals one hour after administration, and one animal also showed slight chemosis. All ocular reactions were fully reversed by 48 hours post exposure. These reactions were slight and below the limit of classification.
Executive summary:

The potential for the test material to cause eye irritation was assessed in an in vivo irritation study in rabbits. The study was performed under GLP conditions in line with standardised guidelines OECD 405, EU Method B.5 and EPA OPPTS 870.2400. The test material was administered to three male New Zealand white rabbits, in a single 1 hour application. Rabbits were assessed over 72 hours for signs of eye irritation, clinical sign of toxicity, mortality and bodyweight gain. Application of the test material to the rabbit’s eye caused slight conjunctival redness and discharge in all three animals, one hour after administration. One animal also showed slight chemosis at one hour. These slight signs of irritation were fully reversed within 48 hours, and subsequently the study was terminated after 72 hours. Under the conditions of the study, the test material was determined to be non-irritating.