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

Endpoint summary

Description of key information

Skin irritation/corrosion

The test material was classified as non-irritant.

Eye irritation

The test material was classified as non-irritant.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

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

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)

Specific details on test material used for the study:

No further details specified in the study report.

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.

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 .

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.

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.

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.

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.

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.

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.

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.

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

 

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2 June 1993 to 6 June 1993.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion"

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Method B5 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)

Specific details on test material used for the study:

No further details specified in the study report.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Specification
Three New Zealand White rabbits were supplied by David Percival Ltd., Maston, Sandbach, Cheshire, U.K. At the start of the study the animals weighed 2.61 - 3.09 g, and were approximately 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 a 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 19 – 23 °C and relative humidity of 58 - 66 %. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A volume of 0.1 ml of the test material, which was found to weigh approx imately 99 mg.

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3 animals

Details on study design:

Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope.
Animals showing evidence of ocular lesions were rejected and replaced.
One rabbit was initially treated. A volume of 0.1 ml of the test material, which was found to weigh approximately 99 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after application, to prevent loss of the test material, and then released.
The left eye remained untreated and was used for control purposes.
Immediately after administration of the test material, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated. In order to minimise pain on application of the test material, one drop of local anaesthetic ("Ophthaine", 0.5% proxymetacaine hydrochloride, E.R. Squibb & Sons , Limited Hounslow, Middlesex, U.K.) was instilled into both eyes of these animals 1 - 2 minutes before treatment.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation, (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 ocular effects were also noted. Examination of the eye was facilitated by use of the light source from a standard ophthalmoscope.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 Hours

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

7 d

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation at the 24-hour observation. Minimal conjunctival redness was noted in one treated eye at the 48-hour observation.
No ocular effects were noted 72 hours after treatment.

Other effects:

Residual test material was noted around the treated eye of all animals throughout the study.
Blue-coloured staining was noted in all treated eyes throughout the study.

JPR BLUE 100: ACUTE EYE IRRITATION TEST IN THE RABBIT

INDIVIDUAL SCORES AND INDIVIDUAL TOTAL SCORES FOR OCULAR IRRITATION

Rabbit Number and Sex (Bodyweight Kg)	IPR = 3				IPR = 0                                  +				IPR = 0                                  +
	151 Female (3.09)				154 Male (2.61)				165 Female (2.83)
Time After Treatment	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr	0 hr	24 hr	48 hr	72 hr
CORNEA E = Degree of Opacity F = Area of Opacity	0S 0	0S 0	0S 0	0S 0	0S 0	0S 0	0S 0	0S 0	0S 0	0S 0	0S 0	0S 0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS D	0S	0S	0S	0S	0S	0S	0S	0S	0S	0S	0S	0S
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE A = Redness B = Chemosis C = Discharge	2S 2 2Re	1S 1 0Re	0S 0 0Re	0S 0 0Re	2S 2 3Re	2S 1 0Re	1S 0 0Re	0S 0 0Re	2S 2 2Re	1S 1 0Re	0S 0 0Re	0S 0 0Re
Score (A + B + C) x 2	12	4	0	0	14	6	2	0	12	4	0	0
Total Score	12	4	0	0	14	6	2	0	12	4	0	0

Key:       hr = hour(s)          IPR = initial pain reaction  Re = residual test material around treated eye

               + = one drop of Ophthaine instilled into each eye 1 – 2 minutes before dosing   S = blue coloured staining

 

JPR BLUE 100: ACUTE EYE IRRITATION TEST IN THE RABBIT

INDIVIDUAL TOTAL SCORES AND GROUP MEAN SCORE FOR OCULAR IRRITATION

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
151 Female 154 Male 165 Female	12 14 12	4 6 4	0 2 0	0 0 0
Group Total	38	14	2	0
Group Mean Score	12.7 1 Hour	4.7 24 Hours	0.7 48 Hours	0.0 72 Hours

 

JPR BLUE 100: ACUTE EYE IRRITATION TEST IN THE RABBIT

INDIVIDUAL & MEAN SCORES FOR CORNEA, IRIS & CONJUNCTIVAE REQUIRED FOR EEC LABELLING REGULATIONS

Rabbit Number & Sex (Bodyweight Kg)	Time After Treatment	Corneal Opacity	Iridial Inflammation	Conjunctival Redness	Conjunctival Chemosis
151 Female (3.09)	24 Hours 48 Hours 72 Hours	0 0 0	0 0 0	1 0 0	1 0 0
Total		0	0	1	1
Mean		0.0	0.0	0.3	0.3
154 Male (2.61)	24 Hours 48 Hours 72 Hours	0 0 0	0 0 0	2 1 0	1 0 0
Total		0	0	3	1
Mean		0.0	0.0	1.0	0.3
165 Female (2.83)	24 Hours 48 Hours 72 Hours	0 0 0	0 0 0	1 0 0	1 0 0
Total		0	0	1	1
Mean		0.0	0.0	0.3	0.3

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test material, JPR BLUE 100, produced a maximum group mean score of 12.7 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 produce positive criteria in any rabbit according to the EEC labelling regulations and was classified as NON IRRITANT to the rabbit eye. 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 eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as Method B5 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 application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. No ocular effects were noted 72 hours after treatment.

 

The test material produced a maximum group mean score of 12.7 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to the Kay and Calandra classification system.

 

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin Irritation/Corrosion

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit.  

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 classified as non-irritant.

Eye irritation

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit.  

A single application of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. No ocular effects were noted 72 hours after treatment.

The test material produced a maximum group mean score of 12.7 and was classified as a mild irritant (Class 4 on a 1 to 8 scale) to the rabbit eye according to the Kay and Calandra classification system.

The test material was classified as non-irritant.

Justification for classification or non-classification

Skin irritation/corrosion

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

Eye irritation

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