lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Remarks:

existing study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010-04-21 to 2010-05-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Meets the criteria for classification as reliable without restriction according to Klimisch et al (1997).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

EC Number:

940-433-0

Molecular formula:

C23H14Li2N4O9S4

IUPAC Name:

lithium hydrogen 7-{(E)-[2-amino-4-(2-naphthyl)-1,3-thiazol-5-yl]diazenyl}naphthalene-1,3,5-trisulfonate (2:1:1)

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

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 Ltd, Loughborough, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.28 or 2.30 kg
- Housing: suspended cages
- Diet : free access to food throughout the study (2030 Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd, Oxon, UK)
- Water : free access to water throughout the study
- Acclimation period: At least 5 days

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

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye remained untreated for use as control

Amount / concentration applied:

A volume of 0.1ml of test material, which was found to weigh 68mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye.

Duration of treatment / exposure:

The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of test material, and then released. The left eye remained untreated and was used for control purposes.

Observation period (in vivo):

Immediately after administration of the test material an assessment of initial pain reaction was made according to a six point scale. Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment according to the Draize Scale for Scoring Ocular Irritation (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).

Any other ocular effects were also noted. Any clinical signs of toxicity, if present, were also noted. An additional observation was made in one treated eye on day 7 to assess the reversibility of the ocular staining.

Individual bodyweights were recorded on day 0 (the day of dosing) and at the end of the observation period.

Number of animals or in vitro replicates:

Initially a single rabbit was treated. After consideration of the ocular responses produced in the first treated animal, a second animal was treated.

Details on study design:

TOOL USED TO ASSESS SCORE: light source from standard opthalmoscope

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 69133

Time point:

other: highest score at 24,48 & 72h

Score:

0

Max. score:

4

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 69176

Time point:

other: highest score at 24, 48 & 72h

Score:

0

Max. score:

4

Remarks on result:

other: pale red coloured staining on lower part of cornea

Results 3

Irritation parameter:

iris score

Basis:

animal: 69133

Time point:

other: highest score at 24,48 & 72h

Score:

0

Max. score:

2

Results 4

Irritation parameter:

iris score

Basis:

animal: 69176

Time point:

other: highest score at 24, 48 & 72h

Score:

0

Max. score:

2

Results 5

Irritation parameter:

chemosis score

Basis:

animal: 69133

Time point:

other: highest score at 24, 48 & 72h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 48h

Results 6

Irritation parameter:

chemosis score

Basis:

animal: 69176

Time point:

other: highest score at 24, 48 & 72h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 48h

Results 7

Irritation parameter:

other: redness

Basis:

other: 69133

Time point:

other: highest score at 24, 48 & 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 8

Irritation parameter:

other: redness

Basis:

animal: 69176

Time point:

other: highest score at 24, 48 & 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 72h

Results 9

Irritation parameter:

other: discharge

Basis:

other: 69133

Time point:

other: highest score at 24, 48 & 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 48h

Remarks on result:

other: staining of fur around treated eye

Results 10

Irritation parameter:

other: discharge

Basis:

other: 69176

Time point:

other: highest score at 24, 48 & 72h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 48h

Remarks on result:

other: staining of fur around treated eye

Irritant / corrosive response data:

Staining of the fur around the treated eyes was noted throughout the study. Pale red coloured staining on the lower part of the cornea was noted in one treated eye at the 48 and 72h observations. The staining did not affect evaluation of the cornea.

No corneal or iridial effects were noted during the study.

Moderate conjunctival irritation was noted in both treated eyes one and 24h after treatment with minimal conjunctival irritation noted at the 48h observation.

No adverse ocular effects were noted in both treated eyes at the 72h observation.

Other effects:

Both animals showed expected gain in bodyweight during the study.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test material following a single application to the eye. The method was designed to meet the requirements of:

OECD Guidelines for the testing of Chemicals No. 405 'Acute Eye Irritation/Corrosion' (adopted 24 April 2002)

Method B5 Acute Toxicity (Eye Irritation) of Commission Regulation (EC) No. 440/2008

Results & Conclusion

The test material produced a maximum group mean score of 12.0 and was classified as a mild irritant (class 4 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system. The test material did not meet the criteria for classification as irritant according to EU labelling regulations Commission Directive 2001/59/EC.