Registration Dossier

Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted following OECD and EU methods and under GLP conditions..

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Substance type: off white powder
- Physical state: solid
- Storage condition of test material: room temperatire until 14 October 2013 and then approximately 4° C in the dark

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.52 to 2.74kg
- Housing: Suspended Cages
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: approximately 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): at least 15
- Photoperiod: 12 hrs dark / 12 hrs light

Test system

Vehicle:
water
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied: volume of 0.1ml, weight approx 48mg
Duration of treatment / exposure:
The test material was administered via syringe into the conjunctival sac of the right eye. The upper and lower eyelids were held together for about one second immediately after treament, to prevent loss of the test item, then released.
Observation period (in vivo):
The 3 rabbits were assessed immediately for pain reaction and assessment of ocular damage/irritation was made approximately 1 hour, 12, 24 and
72 hours following treatement.
Number of animals or in vitro replicates:
3 rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
Test substance could not be removed as was injected into the conjunctival sac of the right eye

SCORING SYSTEM:
The Draize scale was used. 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). For each tissue the score was calculated as follows:

Score for conjunctivae (A + B + C) x 2
Score for iris D x 5
Score for cornea (E x F) x 5


TOOL USED TO ASSESS SCORE: opthalmoscope

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 hour
Score:
15.3
Max. score:
17
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24 hours
Score:
10.7
Max. score:
12
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 48 hours
Score:
6
Max. score:
8
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72 hours
Score:
2.7
Max. score:
8
Reversibility:
fully reversible within: 7 days
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 7 days
Score:
0
Max. score:
0
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Individual and group mean scores for ocular irritation are given in Table 1 (attached below) and Table 2 (attached below).
No corneal effects were noted during the study.
Iridial inflammation was noted in two treated eyes one hour after treatment.

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

One treated eye appeared normal at the 72-Hour observation and two treated eyes appeared normal at the 7-Day observation.

The test item produced a maximum group mean score of 15 .3 and was classified as a moderate irritant (Class 5 on a 1 to 8 scale) to the rabbit eye
according to a modified Kay and Calandra classification system.
Other effects:
Individual body weights and body weight change are given in Table 3 (attached below)
All animals showed expected gain in body weight 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 produced a maximum group mean score of 15 .3 and was classified as a moderate irritant (Class 5 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 Harmonized System of Classification and Labelling of Chemicals or Regulation (EC) No 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.
Executive summary:

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit.

A single application of the test item (Boronic Acid) to the non-irrigate eye of three rabbits produced iridial inflammation and moderate conjunctival irritation. Once treated eye appreared normal at the 72 hour observation and two treated eyes appeared normal at the 7 day observation.