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Administrative data

Endpoint:
eye irritation
Remarks:
other: Preliminary study: In vitro, Main test: In vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 September 2012 to 28 March 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Fully GLP compliant and in accordance with current test guidelines

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 437 (Bovine Corneal Opacity and Permeability Test Method for Identifying Ocular Corrosives and Severe Irritants)
Deviations:
no
Remarks:
Preliminary study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes

Test material

Constituent 1
Test material form:
other: Viscous semi-solid
Details on test material:
Name: MonoFA_TETA_PAA_BADGE_BGE_Adduct
CAS number: 105839-18-7
Batch number: WA521
Purity: 100%
Expiry date: 28 February 2014
Receipt date: 03 September 2012
Storage: stored in a sealed container, at 15 to 25ºC, 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 UK Ltd., Bicester
- Age at study initiation: 17 to 18 Weeks
- Weight at study initiation: Not reported
- Housing: the rabbit was housed in a cage that conformed to the 'Code of Practice for the Housing and Care of Animals Used in Scientific Procedures' (Home Office, London, 1989).
- Diet (e.g. ad libitum): Global Diet 2930C (Harlan Teklad, Bicester, UK), ad libitum
- Water (e.g. ad libitum): Mains water, ad libitum
- Acclimation period: 9 Weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 15 to 22°C
- Humidity (%): > 45%
- Air changes (per hr): The animal room was designed to permit 15 to 20 air changes per hour.
- Photoperiod (hrs dark / hrs light): The rooms were illuminated by fluorescent strip-lights for twelve hours daily.

IN-LIFE DATES: From: 10 December 2012 To: 14 December 2012

Test system

Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
One dose consisting of 0.1 mL of undiluted test article was instilled into the left conjunctival sac of a single New Zealand White rabbit (the sentinel).
Duration of treatment / exposure:
4 Days
Number of animals or in vitro replicates:
1
Details on study design:
Before the animal could be dosed, the pH of the test article was checked. A 50% w/v dispersion in purified water had a pH of 6. Since this was within the acceptable range of pH 2.0 to 11.5, the study continued.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 Hours
Score:
2
Max. score:
2
Reversibility:
not specified
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 Hours
Score:
1
Max. score:
1
Reversibility:
not specified
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 hours
Score:
> 3 - < 4
Max. score:
4
Reversibility:
not specified
Irritant / corrosive response data:
Preliminary test results (In vitro experiment)
Corneas treated with the test article were noted to be slightly opaque.
Corneas treated with the positive control article were cloudy and blistered.
The mean opacity reading for the test article was 7.0, for the negative control was 0.0 and for the positive control was 65.3.
The mean group corrected optical density for the test article was 0.232 for the negative control was 0.0 and for the positive control was 0.588.
The test article produced an IVIS score of 10.47.

In vivo experiment
Dulling of the normal lustre of the cornea was noted 4 hours after instillation, with easily discernible translucent areas of corneal opacity noted from 24 to 72 hours after treatment.
Iridial inflammation was noted at all time points from 30 minutes to 72 hours after instillation.
Moderate conjunctival irritation was noted 30 minutes and 1 hour after instillation with severe conjunctival irritation noted 4 hours after instillation persisting to the end of the observation period.
Maximal conjunctival inflammation (swelling grade 4 and redness grade 3) was noted 24 after instillation with no evidence of recovery within 48 hours. The animal was therefore humanely killed in accordance with the UK Home Office Guidelines on Eye Irritation Tests (published March 2006).

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The test article was considered to be severely irritating to eyes and was classified as Category 1 (causing irreversible effects on the eye) according to the Globally Harmonised System of Classification and Labelling of Chemicals (GHS).
Executive summary:

This study was conducted to determine whether the test article has a potential to cause corrosion or irritation to the eye.

Initially the test article was evaluated using an in vitro test system, the bovine corneal opacity and permeability assay (BCOP). A volume of 750 µL of the test article formulation was applied to each of three corneas followed by a 10 minute incubation at 32 ± 1°C. After this incubation, each cornea was washed with media containing phenol red followed by media without phenol red, the opacities measured and then the anterior chamber emptied. For the permeability endpoint, sodium fluorescein solution was added into the anterior chamber and the corneas were incubated in the vertical position for 1.5 hours ± 5 minutes. Following this period, the media in the posterior chamber was removed and three 350 μL aliquots of this media (per cornea) were analysed for optical density at 490 nanometers (OD490).

A volume of 750 µL of the negative or positive control was similarly applied to further groups of three corneas. These corneas were subject to the procedures detailed above.

Corneas treated with the test article were noted to be slightly opaque. Corneas treated with the positive control article were cloudy and blistered. The mean opacity reading for the test article was 7.0, for the negative control was 0.0 and for the positive control was 65.3. The mean group corrected optical density for the test article was 0.232 for the negative control was 0.0 and for the positive control was 0.588. The test article produced an IVIS score of 10.47 and was not considered to be corrosive or severely irritating to the eye according to the BCOP assay.

An in vivo eye irritation test was therefore conducted. The undiluted test article (0.1 mL) was instilled into one conjunctival sac of a New Zealand White rabbit on Day 1. Ocular reactions were assessed for three days after treatment.

Dulling of the normal lustre of the cornea was noted 4 hours after instillation, with easily discernible translucent areas of corneal opacity noted from 24 to 72 hours after treatment. Iridial inflammation was noted at all time points from 30 minutes to 72 hours after instillation. Moderate conjunctival irritation was noted 30 minutes and 1 hour after instillation with severe conjunctival irritation noted 4 hours after instillation persisting to the end of the observation period.

Maximal conjunctival inflammation (swelling grade 4 and redness grade 3) was noted 24 after instillation with no evidence of recovery within 48 hours. The animal was therefore humanely killed in accordance with the UK Home Office Guidelines on Eye Irritation Tests (published March 2006).

The test article was considered to be severely irritating to eyes and was classified as Category 1 (causing irreversible effects on the eye) according to the Globally Harmonised System of Classification and Labelling of Chemicals (GHS).