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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

25 May 1993 to 8 June 1993 .

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity"

Deviations:

not specified

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Method B3 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 type:

standard acute method

Limit test:

yes

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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Specification
Five male and five female Sprague-Dawley strain rats were supplied by Charles River (UK) ltd., Manston, Kent,U. K. At the start of the study the males weighed 204 – 226 g, and the females 200 – 222 g, and were approximately ten to fourteen weeks old. After a minimum acclimatisation period of at least five days the animals were selected at random and given a unique number within the study by indelible ink marking on the tail and a number written on a cage card.

Husbandry
The animals were housed in suspended polypropylene cages furnished with softwood sawdust. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, Special Diet Services Limited, 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 48 - 54%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours continuous light and 12 hours darkness.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers to expose a skin area of approximately 5 cm x 4 cm.
A group of five male and five female rats were treated with the test material at a dose level of 2000 mg/kg.
The appropriate amount of the undiluted test material, as received, was pre-weighed into a glass vial. The test material was then applied uniformly to an area of shorn skin (approximating to 10% of the total body surface area) which had previously been moistened with distilled water. A piece of surgical gauze was placed over the treatment area and semi -occluded with a piece of self-adhesive bandage (HYPERTIE). The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were caged individually for the 24-hour exposure period.
Shortly after dosing the dressings were examined to ensure that they were securely in place. After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the rest of the study .

Duration of exposure:

24 hours

Doses:

Single dose of 2000 mg/kg

No. of animals per sex per dose:

10 animals (5 males/5 females)

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
The animals were also observed for any dermal reactions after removal of the dressings and subsequently once daily for the remainder of the study.
Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation and subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

Data evaluations included the relationship, if any, between the animals' exposure to the test material and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

No signs of systemic toxicity were noted during the study. Blue coloured staining of the fur was commonly noted.

Body weight:

All animals showed expected gain in bodyweight during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

No signs of skin irritation were noted during the study. Blue coloured staining of the treatment site was commonly noted.

Any other information on results incl. tables

JPR BLUE 100: ACUTE DERMAL TOXICITY (LIMIT TEST) IN THE RAT

INDIVIDUAL CLINICAL OBSERVATIONS AND MORTALITY DATA

Dose Level mg/kg	Animal Number & Sex	Effects Noted After Initiation of Exposure (Hours)				Effects Noted After Initiation of Exposure (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Male	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0
	1-1 Male	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0
	1-2 Male	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0
	1-3 Male	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0
	1-4 Male	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0
	2-0 Female	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0
	2-1 Female	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0
	2-2 Female	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0
	2-3 Female	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0
	2-4 Female	0	0	0	0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	Fs0	0	0	0	0	0

0 = no signs of systemic toxicity

Fs = blue coloured staining of the fur

 

JPR BLUE 100: ACUTE DERMAL TOXICITY (LIMIT TEST) IN THE RAT

INDIVIDUAL DERMAL REACTIONS

Dose Level mg/kg

Animal Number & Sex

Observation

Effects Noted After Initiation of Exposure (Days)

1

2

3

4

5

6

7

8

9

10

11

12

13

14

2000

1-0 Male

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

1-1 Male

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

1-2 Male

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

1-3 Male

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

1-4 Male

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

2-0 Female

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

2-1 Female

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

2-2 Female

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

2-3 Female

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

2-4 Female

Erythema Oedema Other

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

0 0 STA

STA = blue-coloured staining of the treatment site

0 = no signs of dermal irritation

 

JPR BLUE 100: ACUTE DERMAL TOXICITY (LIMIT TEST) IN THE RAT

INDIVIDUAL BODYWEIGHTS AND WEEKLY BODYWEIGHT GAIN

Dose Level mg/kg	Animal Number & Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Male 1-1 Male 1-2 Male 1-3 Male 1-4 Male 2-0 Female 2-1 Female 2-2 Female 2-3 Female 2-4 Female	225 226 204 208 219 220 222 200 209 213	262 275 267 257 274 230 241 203 223 234	300 325 324 310 329 260 270 211 253 257	37 49 63 49 55 10 19 3 14 21	38 50 57 53 55 30 29 8 30 23

 

JPR BLUE 100: ACUTE DERMAL TOXICITY (LIMIT TEST) IN THE RAT

INDIVIDUAL NECROPSY FINDINGS

Dose Level mg/kg	Animal Number & Sex	Time of Death	Macroscopic Observations
2000	1-0 Male 1-1 Male 1-2 Male 1-3 Male 1-4 Male 2-0 Female 2-1 Female 2-2 Female 2-3 Female 2-4 Female	Killed day 14 Killed day 14 Killed day 14 Killed day 14 Killed day 14 Killed day 14 Killed day 14 Killed day 14 Killed day 14 Killed day 14	No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected No abnormalities detected

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal median lethal dose (LD50) of the test material, JPR BLUE 100, in the Sprague-Dawley strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol or risk phrase is required according to EEC labelling regulations.

Executive summary:

A study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley strain rat. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 402 "Acute Dermal Toxicity" referenced as Method B3 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 group of ten animals (five males and five females) was given a single 24 -hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of treatment and were then killed for gross pathological examination.

 

There were no deaths. No signs of systemic toxicity or skin irritation were noted during the study.

All animals showed expected gain in bodyweight during the study.

No abnormalities were noted at necropsy.

 

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley strain rat was found to be greater than 2000 mg/ kg bodyweight. No symbol or risk phrase is required according to EEC labelling regulations.