Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

Administrative data

Endpoint:
eye irritation, other
Remarks:
in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Between 30 July 2001 and 20 August 2001.
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 the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Date of GLP inspection: 28 February 2000 Date of Signature on GLP certificate: 26 April 2000

Test material

Constituent 1
Details on test material:
Sponsor's identification: NBPT
Description: white powder
Batch number: C2001-01
Date received: 19 July 2001
Storage conditions: 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:
David Percival Ltd, Moston, Sandbach, Cheshire, UK.

- Age at study initiation:
Twelve to sixteen weeks old

- Weight at study initiation:
2.0 to 3.5 kg

- Housing:
The animals were individually housed in suspended cages. 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.

- Diet:
STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK

- Water:
Free access to mains drinking water

- Acclimation period:
At least five days


ENVIRONMENTAL CONDITIONS

- Temperature (°C):
17 to 23°C

- Humidity (%):
30 to 70%

- Air changes (per hr):
At least fifteen changes per hour

- Photoperiod (hrs dark / hrs light):
Twelve hours continuous light (06:00 to 18:00) and twelve hours darkness


IN-LIFE DATES:
From: day 1 To:day 3

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye remained untreated and was used for control purposes.
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit):
A volume of 0.1 ml of the test material, which was found to weigh approximately 80 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball.

- Concentration (if solution):
Not applicable. Test material was used as supplied

VEHICLE

- Amount(s) applied (volume or weight with unit):
Not applicable

- Concentration (if solution):
Not applicable

- Lot/batch no. (if required):
Not applicable
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
Approximately 1 hour and 24, 48 and 72 hours following treatment. Additional observations were made on Days 7, 14 and 21 to assess the reversibility of the ocular
effects.
Number of animals or in vitro replicates:
1 animal was tested.
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done):
Not applicable

- Time after start of exposure:
Not applicable


SCORING SYSTEM:
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation from Draize J H (1977, "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49.


TOOL USED TO ASSESS SCORE:

Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
120Male
Time point:
other: Mean 24, 48 and 72 hours
Score:
1.6
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
120 Male
Time point:
other: Mean 24, 48 and 72 hours
Score:
4
Max. score:
4
Reversibility:
not reversible
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
120 Male
Time point:
other: Mean 24, 48 and 72 hours
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
other: redness
Basis:
animal #1
Remarks:
120 Male
Time point:
other: Mean 24, 48 and 72 hours
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
120 Male
Time point:
other: Mean 24, 48 and 72
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
other: Discharge
Basis:
animal #1
Remarks:
120 Male
Time point:
other: Mean 24, 48 and 72
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Dulling of the normal lustre of the cornea was noted in the treated eye one hour after treatment. Scattered or diffuse corneal opacity was noted at the treated eye at the 24-hour observation with translucent corneal opacity at the 48, 72-hour, 7 and 14-day observations. Scattered or diffuse corneal opacity was noted in the treated eye at the 21-day observation.

Iridial inflammation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour and 7-day observations.

Moderate conjunctival irritation was noted in the treated eye one hour after treatment and at the 24, 48, 72-hour, 7 and 14-day observations.

Vascularisation, with a generalised ingrowth of vessels for approximately 3 to 4 mm, was noted in the treated eye at the 7, 14 and 21-day observations with ectropion also noted in the treated eye at the 14-day observation.

The reactions noted at the 21-day observation were considered to be irreversible.

The test material produced irreversible effects and was considered to be CORROSIVE to the rabbit eye.

The test material was also considered to be irritant according to EU labelling regulations Commission Directive 93/21/EEC. It is reasonable to assume that the symbol "Xi", the indication of danger "Irritant" and the highest risk phrase R 41 "RISK OF SERIOUS DAMAGE TO EYES" are therefore required.
Other effects:

Body weight
All animals showed expected gain in bodyweight during the study.

Any other information on results incl. tables

Interpretation of Results

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

Using the numerical data obtained a modified version of the system ( Modified Kay and Calandra Interpretation of Eye Irritation Test was used to classify the ocular irritancy potential of the test material. This was achieved by adding together the scores for the cornea, iris and conjunctivae for each time point for each rabbit. The group means of the total scores for each observation were calculated. The highest of these group means (the maximum group mean score) together with the persistence of the reactions enabled classification of the eye irritancy potential of the test material.

If evidence of irreversible ocular damage is noted, the test material will be classified as corrosive to the eye.

Applicant's summary and conclusion

Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test material produced irreversible effects and was considered to be CORROSIVE to the rabbit eye.
Executive summary:

Introduction. The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method was designed to meet the requirements of the following:

-OECD Guidelines for the Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987)

-Commission Directive 92/69/EEC Method B5 Acute Toxicity (Eye Irritation)

Result. A single application of the test material to the non-irrigated eye of one rabbit produced irreversible effects. Reactions noted included translucent corneal opacity, iridial inflammation, moderate conjunctival irritation, dulling of the normal lustre of the cornea, ectropion and vascularisation with a generalised ingrowth of vessels for approximately 3 to 4 mm.

Conclusion. The test material produced irreversible effects and was considered to be corrosive to the rabbit eye.

The test material was also considered to be irritant according to EU labelling regulations Commission Directive 93/21/EEC. It is reasonable to assume that the symbol "Xi", the indication of danger "Irritant" and the highest risk phrase R 41 "RISK OF SERIOUS DAMAGE TO EYES" are therefore required. Under the GHS it is classified under the health hazard category "Eye Damge 1" with a hazard statement H318: Causes serious eye damage.