Polychloro copper phthalocyanine

Endpoint summary

Description of key information

Skin 
In vivo
- Rabbit, 24 h, occlussive: not irritating (very slight to well defined erythema in 4/6 animals, very slight edema in 1/6 animals, reversible after 7 days; slight desquamation in 2/6 animals after 7 days; Draize; IFREB 1980, comp. OECD 404)
- Rabbit, 24 h, occlussive: not irritating (no effects at any time point in 2/2 animals; Draize; BASF AG 1971, comp. OECD 404)
- Guinea pig: not irritating (Putilina 1976, Val. 4)

Eye
In vivo
- Rabbit, 24 h, substance was not washed out: not irritating (slight conjunctivae redness and chemosis in 5/6 treated eyes, mean score 0.11/0.06; Iritis in 3/6 animals; cornea slightly affectd in 1/6 animals; all effects fully reversible within 72 h Draize, IFREB 1980, comp. OECD 405)
- Rabbit, 24 h, substance was not washed out: not irritating (conjunctivae effects in 2/2 treated and in 2/2 control eyes, mean score 1.0, fully reversib...

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.41

Deviations:

no

Principles of method if other than guideline:

6 male albino New Zealand white rabbits were used for each trial. After clipping, the skin of the left flank of the animals was left intact, the right flank was scarified. The animals were treated for 24 h using occlusive conditions. The application site, treated with the liquid test substance, was covered with a gauze pad and wrapped with adhesive tape. After the application time, the patches/tape were removed. The primary irritation index was evaluated after 25 and 72 hours after start of application of the test material. The animals were observed for one week, at day 7 another reading was made.

GLP compliance:

no

Specific details on test material used for the study:

- Analytical purity: ca. 98 %

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: at the start of the test, the animals weighed between 2.5 and 3.5 kg
- Housing: Rabbits were kept in individual cages (540 x 360 x 315 mm) or in restraining devices
- Diet: 200 g of food per animal per day (Granules Lapin "entretien", Sanders)
- Water: softened and filtrated water ad libitum, automatically given

ENVIRONMENTAL CONDITIONS
- Temperature (°C): minimum 20 °C
- Air changes: ventilation (renewal of air 12 times per hour )
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

other: The rabbits were clipped; the skin of the left flank was left intact ; the skin of the right flank was scarified.

Vehicle:

other: olive oil

Controls:

no

Amount / concentration applied:

0.5 g pure test material, applied in paste form (mixed with olive oil)

Duration of treatment / exposure:

24 hours

Observation period:

7 days

Number of animals:

6

Details on study design:

ADMINISTRATION/EXPOSURE
- The right flank was scarified with a sterile scalpel blade, making three parallel superficial incisions 2 cm long and 0.5 cm apart. The incisions were epidermal.
- The test substance was applied to the rabbit skin, using the right, previously scarified flank and the left intact one, at a rate of 0.5 g test substance per area and animal.
- Occlusion: A loaded gauze patch was applied to intact and scarified skin. The test substance and the gauze pads were kept in contact with the skin by a patch. Patches were then fastened to the body with adhesive tape.
- Vehicle: olive oil (0.5 g in 0.65 ml of neutralized sterilized olive oil per zone)
- Removal of the test substance: after 24 hrs
- Post exposure period: 7 days

EXAMINATION
- Observation period: after exposure at 25 h, at 72 h and 7 days
- Scoring system: readings were made of both scarified and no scarified zones, following the scale proposed by Draize. Only cutaneous reactions observed after treatment of intact skin are considered relevant for hazard assessment and are described in detail.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

of 4 animals

Time point:

other: 24-72 h

Score:

1.12

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: Slight desquamation was seen in 2 animals after 7 days; first reading time point was in fact 25 hours instead of 24 hours.

Irritation parameter:

edema score

Basis:

mean

Remarks:

of 5 animals

Time point:

other: 24-72 h

Score:

0.1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: first reading time point was in fact 25 hours instead of 24 hours.

Irritant / corrosive response data:

Treatment with the test substance resulted in only one out of 6 rabbits in very slight edema after 24 h. The evaluation of erythema after 24 hours was impossible in 2 rabbits due to treatment related colouring of the skin. Very slight to well defined erythema were noticed in 4 rabbits where irritation was reversible after 7 days. Slight desquamation was seen on intact skin in 2/6 animals after 7 days.

Table 1: OECD Draize scores for edema after 24 hours exposure to the test substance:

Rabbit No.		1	2	3	4	5	6
Erythema	25 h	0	*	1	*	2	0
	72 h	1	*	2	*	2	1
	7 d	S	§	0	0	0	S
Edema	25 h	0	0	0	0	1	1
	72 h	0	0	0	0	0	0
	7 d	0	§	0	0	0	0
S = slight desquamation;   C = Formation of a scab without underlying necrosis
* = Reading of erythema was impossible on two rabbits, because of green colouration through the test material
§ = Rabbit No. 2 died on day 6 and was not replaced

Interpretation of results:

GHS criteria not met

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Well documented study, sufficient for assessment.

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500, 42

Principles of method if other than guideline:

This test was used for eye irritation test before OECD guideline 405 was established. It is generally similar to the Draize test, with the following deviations: 100 mg of the test substance was applied to the right eye (OECD recommends a volume of 0.1 ml), 6 animals were used (OECD: 3); observation period was 7 days (OECD: 21).

GLP compliance:

no

Specific details on test material used for the study:

- Analytical purity: ca. 98 %

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: at the start of the test, the animals weighed ca. 2.5 kg
- Housing: Rabbits were kept in individual cages (540 x 360 x 315 mm) or in restraining devices
- Diet: 200 g of food per animal per day (Granules Lapin "entretien", Sanders)
- Water: softened and filtrated water ad libitum, automatically given

ENVIRONMENTAL CONDITIONS
- Temperature (°C): minimum 20 °C
- Air changes: ventilation (renewal of air 12 times per hour)
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye was treated with 50 mg talcum powder and served as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 100 mg
- Concentration: undiluted

Duration of treatment / exposure:

24 h; the substance was not washed out.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

100 mg of the undiluted test substance was applied to the right conjuntival sac of 6 New Zealand White rabbits. The left eye was treated with 50 mg talcum powder and served as control. The substance was not washed out.
Ocular reactions were recorded at 1 h, 24 h, 48 h, 72 h, 96 h and 7 days after instillation using a scoring system, which is convertible into the current OECD Draize scheme. For the evaluation, the scores given in the raw data were converted to Draize scores. The reading time points used for assessment were 24, 48 and 72 hours after application.
Observations of the condition of the cornea were made with the naked eye and also with the aid of an ophtalmoscope of Heine.

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 24-48-72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 24-48-72 h

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 72 h

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 24-48-72 h

Score:

0.11

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

of 6 animals

Time point:

other: 24-48-72 h

Score:

0.06

Max. score:

3

Reversibility:

fully reversible within: 72 h

Irritant / corrosive response data:

The following effects were observed, but were completely reversible within 72 hours:
- Test animals showed slight conjunctiva chemosis and redness, which were completely reversible in 5/6 animals within 48 hours;
- Iris congestion was also observed in 3/6 animals and was also completely reversible within 48 hours in 2 of the animals concerned;
- The cornea was slightly affected in 1/6 animals at 24 h only.

Table 1: Eye irritation parameters according to the method of Draize

Reading time point	Animal 1, treated eye (right)
	Conjunctiva Chemosis	Conjunctiva Redness	Iris score	Cornea score	Additional findings
1 h	1	1	1	0
24 h	1	0	0	0
48 h	1	0	0	0
72 h	0	0	0	0
96 h	0	0	0	0
7 d	0	0	0	0
Reading time point	Animal 2, treated eye (right)
	Conjunctiva Chemosis	Conjunctiva Redness	Iris score	Cornea score	Additional findings
1 h	1	0	1	0
24 h	0	0	0	0
48 h	0	0	0	0
72 h	0	0	0	0
96 h	0	0	0	0
7 d	0	0	0	0
Reading time point	Animal 3, treated eye (right)
	Conjunctiva Chemosis	Conjunctiva Redness	Iris score	Cornea score	Additional findings
1 h	1	1	0	0
24 h	2	1	1	1	discharge
48 h	0	1	1	0
72 h	0	0	0	0
96 h	0	0	0	0
7 d	0	0	0	0
Reading time point	Animal 4, treated eye (right)
	Conjunctiva Chemosis	Conjunctiva Redness	Iris score	Cornea score	Additional findings
1 h	1	1	0	0
24 h	0	0	0	0
48 h	0	0	0	0
72 h	0	0	0	0
96 h	0	0	0	0
7 d	0	0	0	0
Reading time point	Animal 5, treated eye (right)
	Conjunctiva Chemosis	Conjunctiva Redness	Iris score	Cornea score	Additional findings
1 h	1	0	1	0
24 h	1	0	0	0
48 h	0	0	0	0
72 h	0	0	0	0
96 h	0	0	0	0
7 d	0	0	0	0
Reading time point	Animal 6, treated eye (right)
	Conjunctiva Chemosis	Conjunctiva Redness	Iris score	Cornea score	Additional findings
1 h	1	0	0	0
24 h	1	0	0	0
48 h	0	0	0	0
72 h	0	0	0	0
96 h	0	0	0	0
7 d	0	0	0	0

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin

- A Draize test was performed with six White Vienna rabbits, comparable to OECD guideline 404 (IFREB 1980). A 24-hour occlusive exposure to ca. 0.5 g of the test substance in 0.65 ml of neutralized sterilized olive oil per produced the following effects: Treatment with the test substance resulted in only one out of 6 rabbits in very slight edema after 24 h. The evaluation of erythema after 24 hours was impossible in 2 rabbits due to treatment related colouring of the skin. Very slight to well defined erythema were noticed in 4 rabbits where iritation was reversible after 7 days. Slight desquamation was seen on intact skin in 2/6 animals after 7 days.

- In a second report also comparable to OECD guideline 404, rabbits were exposed to a paste containing the moistened test substance (50 %) for 24 h under occlusive conditions (BASF AG 1971). No formation of edema or erythema was observed at any time point. Substance residues were seen on the treated sites until day 7.

Both results should be considered as overpredictive due to the harsh test conditions if compared to actual guideline recommendations (4 h under semiocclusive conditions).

- No irritant effects were also reported in a study with limited validity in guinea pigs (Putilina 1976, Val. 4). However, no study details were available.

Eye

No irritating effects were observed in a Draize test, comparable to OECD guideline 405 (IFREB 1980). Eyes were left unwashed after application of ca. 100 mg of the undiluted, solid test substance and were observed for 7 days. The following effects observed were observed, but were completely reversible within 72 hours: Test animals showed slight conjunctiva chemosis and redness, which were completely reversible in 5/6 animals within 48 hours; iris congestion was also observed in 3/6 animals and was also completely reversible within 48 hours in 2 of the animals concerned; the cornea was slightly affected in 1/6 animals at 24 h only.

A second Draize test was performed with two White Vienna rabbits, comparable to OECD guideline 405 (BASF AG 1971). Eyes were left unwashed after application of ca. 50 mg of the undiluted, solid test substance into the left eye as well as of ca. 50 mg of talcum (control substance) into the right eye of each animal. Observation period was 8 days. The mean score for conjunctivae redness was 1.0 in the treated eye, but was fully reversible within 8 days. In the control eyes, the mean conjunctivae redness score was also 1.0, and was also fully reversible within 8 days. Scores for cornea, iris and chemosis were 0 at any reading time point in the treated eyes.

- No irritant effects were also reported in a study with limited validity in guinea pigs (Putilina 1976, Val. 4). However, no study details were available.

 

 

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A study comparablet to OECD 404 is available for skin irritation. A study comparable to OECD 405 is available for eye irritation.

In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fifteenth time in Regulation (EC) No. 2020/1182.