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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:
19 Sept.-03 Oct. 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted according to an internationally recognised method, and under GLP. The substance is adequately characterised with its purity. Therefore full validation applies.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report date:
2006

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
24 April 2002
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Remarks:
Certificate from 2004-08-19

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
N.B. This batch BWG 60000 was used in several studies with some descriptive information diverging slightly between the reports (for further details, see below in this field and in the following field).

- Appearance:
* Clear yellowish liquid was mentioned in the 2007 and 2008 Notox reports dealing with physico-chemical properties and in the in 2007 Solvay Pharma report dealing with ASRI test.
* Yellow liquid was mentioned in the 2006 and 2007 TNO reports dealing with toxicological endpoints.
- Storage conditions:
* Storage in freezer (=< -15°C) in the dark under nitrogen was mentioned in the 2007 and 2008 Notox reports dealing with physico-chemical properties.
* Storage in freezer (< -10°C) was mentioned in the 2007 Solvay Pharma report dealing with ASRI test.
* Storage at < -18°C (with or without the mention "protected from light") was mentioned in the 2006 and 2007 TNO reports dealing with toxicological endpoints.
- Stability under storage conditions: Stable.

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: SPF bred New Zealand White albino rabbits obtained from Centre Lagro, France.
- Sex: Males.
- Age at study initiation: Young adults.
- Weight at study initiation: 1856, 1784 and 1790 g.
- Housing: Individually housed in stainless steel cages with perforated floor.
- Diet: Standard laboratory diet ad libitum. Each batch of this diet was analysed by the supplier (SDS Special Diets services, Whitham, England) for the nutrients and contaminants and the results were kept available in the archives.
- Water: Tap water (N.V. Hydron Midden-Nederland) ad libitum. Results of routine physical, chemical and rnicrobiological examination of drinking water as conducted by the supplier were kept available in the archives.
The results of diet and water analyses were considered acceptable for this study.
- Acclimation period: 6 days.

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C.
- Humidity: 40 - 70%.
- Air changes: ca. 10 air changes per hour.
- Photoperiod: 12 hours light/12 hours dark cycle.

IN-LIFE DATES:
- Start of study: 19/09/2006.
- Termination of study: 03/10/2006.

Test system

Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.1 mL
- Concentration (if solution): The test substance is a liquid and was used as it is without dilution.
Duration of treatment / exposure:
Single instillation in the conjunctival cul-de-sac of one of the eyes. After administration, the upper and lower eye lids were carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye remaining untreated, served as a control.
Observation period (in vivo):
Observation period of 14 days.
The reactions of the test eyes were judged at ca. one, 24, 48, 72 h and at 7 and 14 days after treatment
Number of animals or in vitro replicates:
3 rabbits (first started with one rabbit).
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing and time after start of exposure: Because of the severe ocular discharge observed, the treated eyes were rinsed with physiological saline daily on the first 3 days of the study. This rinsing was performed to avoid complete closure of the eye-lids by the abundant production of colloidal discharge which often forms a sealing crust.

SCORING SYSTEM:
* CORNEA
> Opacity-degree of density (area most dense taken for reading)
- No opacity = 0
- Scattered or diffuse areas, details of iris clearly visible = 1
- Easily discemible translucent area, details of iris slightly obscured = 2
- Opalescent areas, no details of iris visible, size of pupil barely discemible = 3
- Opaque, iris invisible = 4
> Area of comea affected
- One quarter (or less) but no zero = 1
- Greater than one quarter but less than half = 2
- Greater than half, but less than three quarters = 3
- Greater than three quarters, up to whole area = 4
* IRIS
- Normal = 0
- Folds above normal, congestion, swelling, circumcomeal injection (any or all of these or combination of any thereof) iris still reacting to light (sluggish reaction is positive) = 1
- No reaction to light, haemorrhage, gross destruction (any or all of these) = 2
* CONJUNCTIVAE
> Redness (refers to palpebral and bulbar conjunctivae, excluding comea and iris)
- Vessels normal = 0
- Vessels definitely injected above normal = 1
- More diffuse, deeper crimson red, individual vessels not easily discemible = 2
- Diffuse beefy red = 3
> Chemosis
- No swelling = 0
- Any swelling above normal (including nictitating membrane) = 1
- Obvious swelling with partial eversion of lids = 2
- Swelling with lids about half closed = 3
- Swelling with lids about half closed to completely closed = 4
* OCULAR DISCHARGE
- No discharge = 0
- Any amount different from normal (does not include amounts observed in inner canthus of normal animals) = 1
- Discharge with moistening of the lids and hairs just adjacent to lids = 2
- Discharge with moistening of the lids and hairs, and cons1derable area around the eye = 3

TOOL USED TO ASSESS SCORE
Not specified.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
other: cornea opacity area
Basis:
animal #1
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
other: ocular discharge
Basis:
animal #1
Time point:
24/48 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
other: ocular discharge
Basis:
animal #1
Time point:
72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
other: cornea opacity area
Basis:
animal #2
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
48 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
other: ocular discharge
Basis:
animal #2
Time point:
24/48 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
other: ocular discharge
Basis:
animal #2
Time point:
72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
other: cornea opacity area
Basis:
animal #3
Time point:
24/48/72 h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 7 d
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 d
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
48 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 14 d
Remarks:
Score of 2 after 7 d
Irritation parameter:
other: ocular discharge
Basis:
animal #3
Time point:
24/48 h
Score:
3
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritation parameter:
other: ocular discharge
Basis:
animal #3
Time point:
72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 7 d
Irritant / corrosive response data:
At 1 h after treatment, slight opacity, slight iritis, moderate redness and moderate swelling of the conjunctivae and severe ocular discharge were observed in the rabbits.
At 24, 48 and 72 h after treatment, moderate opacity, slight iritis, severe redness and moderate or severe swelling of the conjunctivae and moderate or severe ocular discharge were observed in the rabbits.
At 7 days after treatment, moderate redness and moderate swelling of the conjunctivae were observed in the three rabbits.
At 14 days after treatment, eye effects had cleared in the rabbits.

Any other information on results incl. tables

Mean values for corneal opacity, iritis, redness and swelling of the conjunctivae of each rabbit scored at 24, 48 and 72 h after treatment with ETFBO:

 

Animal

Corneal opacity

Iritis

Conjunctivae redness

Conjunctivae swelling (chemosis)

#1

2.0

1.0

3.0

2.7

#2

2.0

1.0

3.0

2.3

#3

2.0

1.0

3.0

2.7

Applicant's summary and conclusion

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Conclusions:
Based on the mean scores following grading at 24, 48 and 72 hours after instillation of the test material and considering full reversibility after 14 days, ETFBO was demonstrated to be irritating to eyes and should be classified in Category 2 for serious eye damage/eye irritation (H319: Causes serious eye irritation). However, applying such a classification would lead to an inconsistency with the labelling resulting from the classification applied for skin corrosion (Category 1, H314: Causes severe skin burns and eye damage). As a matter of consistency at the level of the SDS and the labelling, it was therefore decided to severize the classification for the hazard class serious eye damage/eye irritation and to classify ETFBO in Category 1 (H318: Causes serious eye damage).
Executive summary:

The potential for serious eye damage/eye irritation was investigated in a GPL-compliant study performed according to OECD test guideline 405.

 

The study was carried out with three male New Zealand White albino rabbits. Each rabbit was treated as follows: an amount of ca. 0.1 ml of the test substance was instilled in the conjunctival cul-de-sac of one of the eyes. After administration, the upper and lower eye lid were carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material. The other eye remaining untreated, served as a control. The reactions of the test eyes were judged at ca. one, 24, 48, 72 h and at 7 and 14 days after treatment.

 

At 1 h after treatment, slight opacity, slight iritis, moderate redness and moderate swelling of the conjunctivae and severe ocular discharge were observed in the rabbits. At 24, 48 and 72 h after treatment, moderate opacity, slight iritis, severe redness and moderate or severe swelling of the conjunctivae and moderate or severe ocular discharge were observed in the rabbits. In the three rabbits, the mean scores following grading at 24, 48 and 72 h for corneal opacity, iritis, conjunctivae redness and conjunctivae swelling (chemosis) were of 2.0, 1.0, 3.0 and 2.3 - 2.7, respectively. At 7 days after treatment, moderate redness and moderate swelling of the conjunctivae were still observed in the three rabbits. At 14 days after treatment, eye effects had cleared in all the rabbits.

 

According to the GHS criteria and based on the mean scores following grading at 24, 48 and 72 hours after instillation of the test material and considering full reversibility after 14 days, ETFBO was demonstrated to be irritating to eyes and should be classified in Category 2 for serious eye damage/eye irritation (H319: Causes serious eye irritation). However, applying such a classification would lead to an inconsistency with the labelling resulting from the classification applied for skin corrosion (Category 1, H314: Causes severe skin burns and eye damage). As a matter of consistency at the level of the SDS and the labelling, it was therefore decided to severize the classification for the hazard class serious eye damage/eye irritation and to classify ETFBO in Category 1 (H318: Causes serious eye damage).