Coupling reaction products of 3,3’-dichlorobiphenyl-4,4’-bis(diazonium) dichloride with N-(2,4-dialkylphenyl)-3-oxobutanamide and potassium 4-[(3-oxobutanoyl)amino]substituted benzene and their basic aluminium and earth alkali metal salts

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 December 2007-30 December 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted according to OECD and EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2400 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): S-500
- Physical state: yellow powder
- Lot/batch No.: MF1456-2345
- Expiration date of the lot/batch: 18 August 2011
- Storage condition of test material: At room temperature in the dark
- 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: Harlan, Horst, The Netherlands
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1 kg
- Housing: Individually in labeled cages with perforated floors
- Diet (e.g. ad libitum): Pelleted diet for rabbits approximately 100 grams per day. Hay was provided at least three times a week.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.6 – 21.7
- Humidity (%): 42 - 60
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the other eye of each rabbit remained untreated and served as the reference control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): approx. 0.1 mL ( avg 45.8 mg)

Duration of treatment / exposure:

After 24-hours observation, a solution of 2% fluorescein in water was instilled into both eyes of each animal to determine corneal epithelial damage.

Observation period (in vivo):

3 days

Number of animals or in vitro replicates:

3

Details on study design:

SCORING SYSTEM: according to OECD 405


TOOL USED TO ASSESS SCORE: fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

0

Results 2

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

0

Results 3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 24h

Results 4

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

other: 24, 48 and 72h

Score:

0 - 0.3

Max. score:

1

Reversibility:

fully reversible within: 48h

Irritant / corrosive response data:

No iridial irritation or corneal opacity were observed, and treatment of the eyes with 2% fluorescein, 24 hours after test substance instillation revealed no corneal epithelial damage.
There was no evidence of ocular corrosion.
Remnants of the test substance were present in the eye on Day 1 and on the outside of the eyelids on Days 1 and 2.
Yellow staining of the fur on the head and paws, caused by the test substance, was noted throughout the observation period.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on these results, S-500 does not have to be classified and has no obligatory labeling requirement for eye irritation according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2004) and EC criteria for classification and labeling requirements for dangerous substances and preparations (Council Directive 67/548/EEC).