Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 21 January 2013 and 07 February 2013.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: 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 relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

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
Test material form:
other: liquid
Details on test material:
Sponsor's identification : Sodium Glucoheptonate (EC 250-480-2)
Description : dark brown liquid
Lot number : 921000100
Purity : 49.5%
Date received : 09 February 2012
Expiry date : 09 February 2015
Storage conditions : room temperature in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.31 to 2.88 kg and were twelve to twenty weeks old. After an acclimatisation period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 17 to 23°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Test system

Controls:
other: The left eye of each animal remained untreated and was used for control purposes.
Amount / concentration applied:
Initially, a single rabbit was treated. A volume of 0.1 ml of the test item was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test item, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test item, an assessment of the initial pain reaction was made.
Observation period (in vivo):
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, an additional observation was made on day 7
Number of animals or in vitro replicates:
3 animals, 1 animal treated initially followed by 2 more
Details on study design:
SCORING SYSTEM: The scoring system used was that used by Kay JH and Calandra. The results were also interpreted according to the Globally Harmonised System of Classification and Labelling of Chemicals and Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.

TOOL USED TO ASSESS SCORE:
The numerical values corresponding to each animal, tissue and observation time were recorded. The data relating to the conjunctivae were designated by the letters A (redness), B (chemosis) and C (discharge), those relating to the iris designated by the letter D and those relating to the cornea by the letters E (degree of opacity) and F (area of cornea involved).

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Remarks:
72891 male
Basis:
mean
Time point:
other: of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects observed
Irritation parameter:
cornea opacity score
Remarks:
72939 male
Basis:
mean
Time point:
other: of 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects seen
Irritation parameter:
cornea opacity score
Remarks:
72940 Male
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: no effects seen
Irritation parameter:
conjunctivae score
Remarks:
male 72891
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Remarks:
72939 male
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
conjunctivae score
Remarks:
male 72940
Basis:
mean
Time point:
other: 24,48 and 72 hours
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Remarks:
72891 male
Basis:
mean
Time point:
other: of 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
iris score
Remarks:
72939 male
Basis:
mean
Time point:
other: 24, 38 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
iris score
Remarks:
72940 male
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
chemosis score
Remarks:
72891 male
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
chemosis score
Remarks:
72939 male
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritation parameter:
chemosis score
Remarks:
72940 male
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Irritant / corrosive response data:
Yellow/brown coloured staining of the fur was noted around one treated eye during the study.

No corneal effects were noted during the study.

Iridial inflammation was noted in all treated eyes one hour after treatment.

Moderate conjunctival irritation was noted in two treated eyes with minimal conjunctival irritation noted in one treated eye one hour after treatment. Minimal conjunctival irritation was noted in all treated eyes at the 24 and 48-Hour observations and persisted in one treated eye at the 72-Hour observation.

Two treated eyes appeared normal at the 72-Hour observation and one treated eye appeared normal at the 7-Day observation.

Despite the effects seen, the test item does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.
Other effects:
Bodyweight:
One animal showed bodyweight loss and two animals showed expected gain in bodyweight during the study.

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.
Executive summary:

Introduction: The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit. The method was designed to be compatible with the following:

OECD Guidelines for the Testing of Chemicals No. 405 “Acute Eye Irritation/Corrosion” (adopted 24 April 2002).

Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

Initial considerations. Available information indicated that the test item had the potential to produce severe effects in a rabbit eye and to confirm this initial assessment, a Rabbit Enucleated Eye Test was performed prior to the in vivo test. The results are given in Appendix 4 and indicated that the test item was unlikely to cause severe ocular irritancy.

Result. A single application of the test item to the non-irrigated eye of three rabbits produced iridial inflammation and minimal to moderate conjunctival irritation. Two treated eyes appeared normal at the 72-Hour observation and one treated eye appeared normal at the 7-Day observation.

Conclusion: The test item produced a maximum group mean score of 12.3 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test item does not meet the criteria for classification according to the Globally Harmonised System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Dangerous Substances.