Cuprate(4-), [C-(aminosulfonyl)-C-[[[2-[[4-chloro-6-[(2,5-disulfophenyl)amino]-1,3,5-triazin-2-yl]amino]ethyl]amino]sulfonyl]-29H,31H-phthalocyanine-C,C-disulfonato(6-)-N29,N30,N31,N32]-, sodium salts

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 May 1993 to 2 June 1993.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion"

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

Method B4 in Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Cuprate(4-), [C-(aminosulfonyl)-C-[[[2-[[4-chloro-6-[(2,5-disulfophenyl)amino]-1,3,5-triazin-2-yl]amino]ethyl]amino]sulfonyl]-29H,31H-phthalocyanine-C,C-disulfonato(6-)-N29,N30,N31,N32]-, sodium salts

EC Number:

689-188-9

Cas Number:

149343-84-0

Molecular formula:

C32H24N12O8S4Cu to C76H56N28O32S12Cl4Na8Cu

IUPAC Name:

Cuprate(4-), [C-(aminosulfonyl)-C-[[[2-[[4-chloro-6-[(2,5-disulfophenyl)amino]-1,3,5-triazin-2-yl]amino]ethyl]amino]sulfonyl]-29H,31H-phthalocyanine-C,C-disulfonato(6-)-N29,N30,N31,N32]-, sodium salts

Test material form:

solid: particulate/powder

Details on test material:

Identification: JPR Blue 100
Description: Blue powder
Chemical Name: Cuprate(2-),[2-[[4-chloro-6-[[2-[(29H,31H-phthalocyaninylsulphonyl)amino]ethyl]amino]-1,3,5-triazin-2-yl]amino]-1,4-benzenedisulphonato(4-)-N29,N30,N31,N32]-mono(or bis)aminosulphonyl mono (or di)sulpho derivs., sodium salts.
Lot Number: 303001
Purity: 95.2%
Major Impurities: H2o, NaCl, Na2SO4
Date Received: 30 March 1993
Container: Opaque plastic jar x 7
Storage conditions: Room temperature

Specific details on test material used for the study:

No further details specified in the study report.

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Specification
Three New Zealand White rabbits were supplied by David Percival ltd., Moston, Sandbach, Cheshire, U.K. At the start of the study the animals weighed 2.45 - 2.74 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.

Husbandry
The animals were individually housed in suspended metal cages.
Free access to mains drinking water and food. (RABMA Rabbit Diet, Special Diet Services ltd., Witham, Essex, U.K.) was allowed throughout the study.
The animal room was maintained at a temperature of 18 – 23 °c and relative humidity of 51 - 65%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give continuous 12 hours light and 12 hours darkness.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3

Details on study design:

On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2.5 cm gauze patch and placed in position on the shorn skin. The patch was secured in position with a strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton wool soaked in diethyl ether.
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize J.H. (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics".
Any other skin reactions, if present, were also recorded.
An additional observation was made on day 7 to assess the reversibility of skin reactions .

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

24/48/72 h

Score:

1.2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal.

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal.

Results 3

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal.

Results 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal.

Results 5

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal.

Results 6

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal.

Results 7

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal.

Irritant / corrosive response data:

Very slight erythema was noted at two treated skin sites one hour after patch removal and at all treated skin sites at the 24, 48 and 72-hour observation. The erythema extended beyond all treated skin sites during this time.
Very slight oedema was noted at one treated skin site at the 24 and 48-hour observations.
Desquamation was noted at all treated skin sites seven days after treatment.

Other effects:

Light blue-coloured staining caused by the test material was noted at all treated skin sites following patch removal. The staining did not affect evaluation of skin responses.

Any other information on results incl. tables

JPR BLUE 100: ACUTE DERMAL IRRITATION TEST IN THE RABBIT

INDIVIDUAL SKIN REACTIONS

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex (Bodyweight Kg)			Total
		198 Female (2.74)	202 Male (2.45)	203 Female (2.45)
Erythema/Eschar Formation	1 Hour 24 Hours 48 Hours 72 Hours 7 Days	1 STA 1 RSTA 1 RSTA 1 STA 0 DSTA	1 STA 1 RSTA 1 RSTA 1 STA 0 DSTA	0 STA 1 RSTA 1 RSTA 1 RSTA 0 DSTA	(2) 2 (3) 3 (0)
Oedema Formation	1 Hour 24 Hours 48 Hours 72 Hours 7 Days	0 0 0 0 0	0 1 1 0 0	0 0 0 0 0	(0) 1 (1) 0 (0)
Sum of 24 and 72-Hour Readings (S)		7
Primary Irritation Index (S/6)		7/6 = 1.2
Classification		MILD IRRITANT

( ) = Total values not used for calculation of primary irritation index

D = desquamation

STA = light blue-coloured staining

R = reaction extends beyond treatment site

 

INDIVIDUAL DAILY AND INDIVIDUAL MEAN SCORES FOR DERMAL IRRITATION FOLLOWING 4-HOUR EXPOSURE REQUIRED FOR EEC LABELLING REGULATIONS

Skin Reaction	Reading (Hours)	Individual Scores –Rabbit Number and Sex (Bodyweight Kg)
		198 Female (2.74)	202 Male (2.45)	203 Female (2.45)
Erythema/Eschar Formation	24 48 72	1 1 1	1 1 1	1 1 1
Total		3	3	3
Mean Score		1.0	1.0	1.0
Oedema Formation	24 48 72	0 0 0	1 1 0	0 0 0
Total		0	2	0
Mean Score		0.0	0.7	0.0

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test material, JPR BLUE 100, produced a primary irritation index of 1.2 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material did not produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as NON IRRITANT to rabbit skin. No symbol and risk phrase are therefore required.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals {1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as Method B4 in Commission Directive 92/ 69/ EEC {which constitutes Annex V of Council Directive 67/ 548/ EEC).

 

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/ 548/ EEC {as adapted to technical progress by Commission Directive 91/325/EEC} .

 

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema and very slight oedema. Desquamation was noted at all treated skin sites seven days after treatment.

 

The test material produced a primary irritation index of 1.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

 

The test material was also classified as non-irritant according to EEC labelling regulations. No symbol and risk phrase are required.