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Toxicological information

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:
2014-03-11 until 2014-03-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, no restrictions, fully adequate for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
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:
solid: crystalline
Details on test material:
- Physical state: Yellowish crystals
- Purity test date: 19 September 2013
- Expiration date of the lot/batch: End September 2015
- Stability under test conditions: Stable until end September 2015
- Storage condition of test material: Room temperature (<30°C), protected from light and humidity

Test animals / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S&K-LAP Kft., 2173 Kartal, Császár út 135, Hungary
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 2992-3077 g
- Housing: Individually housed in AAALAC approved metal wire rabbit cages
- Diet: UNI diet for rabbits ad libitum. Source of feed: Agribrands Europe Hungary PLC, H-5300 Karcag, Madarasi út, Hungary
- Water: Tap water ad libitum
- Acclimation period: At least 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.0–20.4
- Humidity (%): 24-48
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 11 March 2014 To: 18 March 2014

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated contralateral eye served as the control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 g
Duration of treatment / exposure:
Single instillation (eye lids gently held together for at least one second in order to prevent loss of the material).
Observation period (in vivo):
72 hours (scored approximately 1, 24, 48, 72 hours after installation).
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes, rinsed with physiological saline.
- Time after start of exposure: 1 hour after instillation

SCORING SYSTEM: The eye irritation scores were evaluated according to the scoring system by Draize (1977) and OECD 405 (02 October 2012)

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
2
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: mean of 24, 48, 72 h
Score:
0
Max. score:
4
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: mean of 24, 48, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: mean of 24, 48, 72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: mean of 24, 48, 72 h
Score:
0.7
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritant / corrosive response data:
No Initial Pain Reaction/Pain reaction (IPR/PR) was observed.

1 hour after treatment: Conjunctival redness (score 1 or 2), chemosis (score 1 or 2) and discharge (score 3) were seen in all rabbits. Conjunctival redness (score 1) and discharge (score 1) were seen in all rabbits at 24 hours after treatment. Conjunctival redness (score 1) was seen in two rabbits and discharge (score 1) was seen in one rabbit at 48 hours after treatment. All symptoms had fully reversed in all animals by the 72 hours observations.

Fluorescein staining was negative in all animals at 24, 48 and 72 hours after instillation.
.
The control eyes were symptom-free during the study.
Other effects:
No mortality, no clinical signs of systemic toxicity and bodyweights of all rabbits were within the normal range of variability.

Any other information on results incl. tables

Table 1: Eye irritation scores according to the Draize scheme

Time

Cornea

Iris

Conjunctiva

 

 

 

 

Redness

Chemosis

 

Animal number

832

849

864

832

849

864

832

849

864

832

849

864

after 1 hour

0d

0

0

0

0

0

1

2

2

1

2

1

after 24 hours

0d

0d

0d

0

0

0

1

1

1

0

0

0

after 48 hours

0

0d

0d

0

0

0

1

0

1

0

0

0

after 72 hours

0

0d

0

0

0

0

0

0

0

0

0

0

mean scores 24-72 hours

0

0

0

0

0

0

0.7

0.3

0.7

0

0

0

d conjunctival discharge

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test item was graded as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to the modified Kay and Calandra classification system.
Executive summary:

The primary eye irritation effect of the test item was evaluated according to OECD test guideline no.: 405 (2012), EPA OPPTS 870.2400 (1998), Directive 2004/73/EC B.5 (L 152 2004) and EC No 440/2008, B.5 (2008). The test item was administered as an installation of a single dose of 0.1 g into the conjunctival sac of the left eye of 3 adult male New Zealand White rabbits. The untreated right eye served as the control. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test material installation in all animals. Observations with fluorescein staining were made approximately 24 hours before treatment and then 24, 48 and 72 hours after the treatment in all animals. Rabbits were treated with analgesic and anaesthetic as per the regulatory guideline. Results obtained from these three animals were used to classify the test item for irritation potential.

No Initial Pain Reaction/Pain reaction (IPR/PR) was observed. Conjunctival redness (score 1 or 2), chemosis (score 1 or 2) and discharge (score 3) were seen in all rabbits at 1 hour after treatment. Conjunctival redness (score 1) and discharge (score 1) were seen in all rabbits at 24 hours after treatment. Conjunctival redness (score 1) was seen in two rabbits and discharge (score 1) was seen in one rabbit at 48 hours after treatment. All symptoms had fully reversed in all animals by the 72 hours observations. Fluorescein staining was negative in all animals at 24, 48 and 72 hours after instillation. The control eye of animals was symptom-free during the study. No mortality occurred during the study. The bodyweights of all rabbits were considered to be within the normal range of variability.

The test item was graded as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to the modified Kay and Calandra classification system.