Bis and tris and tetra (4-{bis[4-(dimethylamino)phenyl]methylene}-N,N-dimethylcyclohexa-2,5-dien-1-iminium) [12,21-dihydro-29H,31H-phthalocyanine-bis and tris and tetrasulfonato-k4N29,N30,N31,N32]cuprate

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2008

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The reliability is rated 2 because this is the result of a read-across from a very close analogue substance. Based on the structure and on the profile impurities, irritating properties are not supposed to be different between the two substances (the source molecule and the target molecule). The reliability of the crossed-reference substance's result is rated 1 because the study followed the standard guideline of reference (OECD 405), which describes a procedure designed to evaluate this endpoint, the results were reviewed for reliability and assessed as valid, and the study was conducted under GLP condition.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Mono and bis and tris{tris[4-(mono and dimethylamino)phenyl]methylium} [12,21,30,32-tetrahydro-29H,31H-phthalocyanine-mono, bis and trisulfonato-k4N29,N30,N31,N32]cuprate

IUPAC Name:

Mono and bis and tris{tris[4-(mono and dimethylamino)phenyl]methylium} [12,21,30,32-tetrahydro-29H,31H-phthalocyanine-mono, bis and trisulfonato-k4N29,N30,N31,N32]cuprate

Constituent 2

Reference substance name:

700-578-0

EC Number:

700-578-0

IUPAC Name:

700-578-0

Details on test material:

- Name of test material : Sepisol Fast Violet 2B
- Substance type: Organocopper salt
- Physical state/ appearance: dark violet powder
- Lot/batch No.: 423393
- Storage condition of test material: ambient temperature and 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: Elevage GRIMAUD, 49459, FRANCE
- Weight at study initiation: 2.610 kg the day of the test material application
- Housing: Singly housed, in suspended stainless steel cage (60cm x 45 cm x 32 cm)
- Diet: granules Starlap Unic Robe (EVIALIS, 37018 Tours, France)
- Water : ad libitum
- Acclimation period: 5 days at least

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/-3
- Humidity (%): 50 +/- 20
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 hrs/1 2 hrs

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye of the animal serves as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0,1 g

Duration of treatment / exposure:

single exposure followed by contention period of one hour

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

1 animal.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No removal by washing

SCORING SYSTEM: according to OECD 405

TOOL USED TO ASSESS SCORE: macroscopic examination and examination with fluorescein

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean score: 24,48 and 72h after application

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Results 2

Irritation parameter:

other: Redness

Basis:

animal #1

Time point:

other: mean score: 24,48 and 72h after application

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 21 days

Results 3

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean score: 24h, 48 and 72 h after application

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 21 days

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean score: 24h, 48h, 72h after application

Score:

2

Max. score:

2

Reversibility:

not fully reversible within: 21 days

Irritant / corrosive response data:

The test item leads to a non-reversible irritation

Any other information on results incl. tables

Scores

Chemosis

Chemosis score for animal 1	Observation period (after application)
	1h	24h	48h	72h	Mean	Day 5 up to 10	Day 11 up to 20	Day 18 up to 20	Day 21
	3	4	4	4	4.0	4	3	2	1

Redness

Redness Score for Animal 1	Observation period (after application)
	1h	24h	48h	72h	Mean*	Day 5 up to 21
	2	3	3	3	3	3

Iris

Iris Score for Animal 1	Observation period (after application)
	1h	24h	48h	72h	Mean*	Day 5 up to 21
	1	1	1	1	1	1

Cornea

Cornea Score for Animal 1	Observation period (after application)
	1h	24h	48h	72h	Mean*	Day 5 up to 21
	0	2	2	2	2.0	2

* mean of observed values at 24, 48 and 72h after application

Clinical observations:

Time Reading	Comments
	Animal #1
Day 1 (first hour)	Nothing to report
Day 2 up to day 8	Burned nictitating membrane - Opacity visible to the naked eye -Alopecia
Day 9 up to Day 14	Mild burning of the nictitating membrane - Corneal opacity visible to the naked eye - Presence of a pannus and alopecia
Day 15 up to Day 21	Mild burning of the nictitating membrane - Corneal opacity visible to the naked eye - Presence of a pannus and alopecia – Mild cornea edema

JUSTIFICATION FOR THE READ-ACROSS

The crossed reference substance Sepisol Violet 2B has also been registered under REACH. The physico-chemical properties of both Sepisol Fast Violet 2B and 3B have been compared (especially because the measurement methods were similar) and assessed as very similar.

Ecotoxicological endpoints have exhibited similar outcomes. Few toxicological endoints have shown different results (oral toxicity and skin sensitisation but the method used were not necessarily equivalents).

The sub-structure of the molecule of Sepisol Violet 3B is made of 3 di-methylamino units while Sepisol Violet 2B is made of a combination of 3 units of either dimethylamino or methylamino unit (a schematic representation is provided below). The two molecules have the same fonctional groups but not in the same proportion.

The impurities profile of the source molecule and of the target are similar.

It is then expected that the potency for eye irritation is the same for the two substances.

Applicant's summary and conclusion

Interpretation of results:

highly irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Based on a read-across with Sepisol Fast Violet 2B which was found to be classified as eye damage category 1 (according to the CLP regulation CE1272/2008), it is reasonably expected that Sepisol Fast Violet 3B will also be highly irritating for the eyes of rabbits and should be classified as category 1 (eye damage).

Executive summary:

The aim of this study was to assess qualitatively and quantitatively irritancy or corrosion and the delay of appearance of the effects after a single application of 0.1 g of the pure test material named Sepisol Fast Violet 2B as supplied on eye in one rabbit. The assay was performed according to the OEDC guideline n° 405.

Ocular reactions (redness and chemosis of conjunctivae, iris and cornea lesions) were scored 1h, 24h, 48h and 72 h after application and until the end of the period study (D21). The untreated eye served as control.

The results for the mean score were as follows (mean score 24h, 48h and 72h after application): chemosis: 4.0; redness: 3.0; Iris:1.0 and

Cornea: 2.0. In regards of the results observed and the irreversibility of the lesions at the end of the observation period on D21, the study was not carried out on 2 other rabbits for ethical reasons.

According to the criteria defined in the CLP regulation (EC 1272/2008), the test material is found to be classified as eye damage category 1.