[1,3,8,16,18,24-hexabromo-2,4,9,10,11,15,17,22,23,25-decachloro-29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]copper

Endpoint summary

Description of key information

Non irritant by read-across

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

The target substance is a polychloro/bromo copper phthalocyanine pigment (Br = 6, Cl = 10, fully substituted).

Hazard assessment is based on experimental data on a range of (un)subsituted copper phthalocyanine pigments. The unsubstituted copper phthalocyanine (Pigment Blue 15) and the almost completely chlorinated copper phthalocyanine (Pigment Green 7) and the mixed polychloro/bromo version (CAS 68512 -13 -0) are well examined. High quality data is available for copper phthalocyanines with a lower chlorine or less defined substitution grade. A number of chlorinated copper phthalocyanine pigments may actually be described by the same CAS number as some CAS names provide a broad and definition of substance identity. In this specific case, the target substance is a mixed bromo/chloro copperphthalocyanine with a defined ratio of both halogens, whereas for the main analoge (CAS 68512 -13 -0), the ratio of both halogens is undefined. Both are fully substituted.

 Neither the non-chlorinated nor the low or highly or completely chlorinated/brominated copper phthalocyanines require classification for skin irritation based on GHS criteria.

 The studies performed according to the OECD 404 protocol showed no or very slight and quickly reversible effects.

In studies performed according to the more stringent US Federal Register protocol (24h occlusive treatment), slight edema were observed. Erythema could not be scored as the test material resulted in a blue staining of the skin. Both intact and scarified skin sites were tested, and no difference in effects were noted between them.

In the study with the high chlorinated copper phthalocyanine, 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.

Copper phthalocyanine and the low chlorinated copper phthalocyanine were tested in rabbits according to OECD guideline 404 and under GLP. Other studies were performed according to the US Federal Register procedure which requires the more stringent 24h occlusive exposure if rabbits. These studies were performed prior to the establishment of GLP and OECD testing guidelines. They are described in adequate detail to allow assessment and are assigned a validity score of 2.

 

CAS No. 68512-13-0:

The commercial form of the green pigment was tested for skin irritation in rabbits prior to the introduction of GLP and OECD testing guidelines (BASF 1978). The study was performed according the procedures published in the US Federal Register Vol. 38. The procedure for skin irritation uses a more stringent 24h occlusive exposure with short observation period of 72h.

In the study for skin irritation, green staining of the skin interfered with erythema staining after 24h and also in some animals after 72h. No erythema were observed in animals for which scoring was possible. No edema was observed at either time point in any animal. After 7 days, the hypoderm and muscle under the treated sites were examined and no adverse findings were observed.

Considering the clear absence of effects, the skin irritation study is suitable to allow the conclusion "not classified" according to GHS criteria.

 

CAS No. 147-14-8 (Pigment Blue 15):

An OECD 404 and GLP compliant study was performed to assess the irritancy potential of Pigment Blue 15 to the skin of the New Zealand White rabbit (Safepharm 2004). A single 4-hour, semi-occluded application of 0.5 g the blue powder (moistened with 0.5mlof distilled water)to the intact skin of three rabbits produced very slight erythema. No evidence of skin irritation was noted at the 48-hour observation. The test material produced a primary irritation index of 0.5. No corrosive effects werenoted.Blue-colouredstaining wasnotedatalltreatedskinsites throughoutthestudy. Thisdidnotaffectevaluation of skinreactions.

 

A Draize test was performed with four White Vienna rabbits, comparable to OECD guideline 404 (BASF AG 1971). A 20-hour occlusive exposure to ca. 1 ml of the test substance (moistured with water and mixed to a paste) produced no effects (overall scores of 0 for all readings 24, 48 and 72 h).

 

In a third report, rabbits were exposed to 0.5 g of the powdered test material, mixed to a paste with polyethylene glycol before application, for 24 h under occlusive conditions (Huntingdon Research Centre 1973, Val. 4). According to the author, no signs of irritation were seen during the 72 hours observation period at the intact skin of any animal.

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

 

CAS No. 1328-53-6 (Pigment Green 7):

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 irritation 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).

 

CAS No. 574-93-6 (Pigment Blue 16):

A Draize test was performed with three New Zealand White rabbits, comparable to OECD guideline 404 (BASF AG 1979). A 24-hour occlusive exposure to ca. 0.5 ml of the undiluted test material produced the following effects: The evaluation of erythema was impossible in all rabbits due to treatment related colouring of the skin. No to moderate edema was seen in 3 animals, the mean score for edema was 0.83. In one animal the effect was not fully reversible within 8 days.

 

CAS No. 27614 -71 -7:

A test was performed with three New Zealand White rabbits, acc. to OECD guideline 404 (Aventis Pharma 2001). A 4-hour semi-occlusive exposure to 0.5 g test material, pasted with 0.4 ml sesame oil produced no signs of irritation on the clipped skin of any rabbit during the whole study period.

Eye irritation

The target substance is a polychloro/bromo copper phthalocyanine pigment (Br = 6, Cl = 10, fully substituted). The three source chemicals which have been tested for eye irritation are the low chlorinated (n=4) and the high (n=14-16) chlorinated copper phthalocyanine and the mixed polychloro/bromo (in sum n= 16) copper phthalocyanine.   All substances are solids which do not melt at temperatures below 400°C. Data on non-chlorinated phthalocyanines (Pigment Blue 15 and 16) is given as further evidence.

Neither the non-chlorinated nor the low or highly or completely chlorinated/brominated copper phthalocyanines require classification for eye irritation based on GHS criteria.

 

Effects are mostly restricted to slight transient irritation of the conjunctivae. The most prominent (but still clearly below the classification threshold) findings were observed in one study with the highly chlorinated copper phthalocyanine (Pigment Green 7):

- 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.

All findings were completely reversible within 72 h.

 

Most studies were performed according to the US Federal Register protocol, which is basically identical with that of OECD guideline 405. The US protocol requires higher number of animals and observation is only performed up to 8 days. However, since findings were reversible within that period, this deviation does not affect the reliability of the study.

Studies were mostly performed prior to the introduction of GLP, but the reporting detail is adequate for assessment. They have been assigned the validity score of 2.

The study performed with the low chlorinated copper phthalocyanine was performed according to OECD 405 and under GLP.

 

 

CAS No. 68512-13-0:

The commercial form of the green pigment was tested for skin and eye irritation in rabbits prior to the introduction of GLP and OECD testing guidelines (BASF 1978). The studies were performed according the procedures published in the US Federal Register Vol. 38. The procedure for eye irritation is identical to the later adopted OECD guideline 405. No findings on rabbit eyes were observed for any parameter (iris, conjuctivae, cornea) at any time point in any animal.

CAS No. 147-14-8 (Pigment Blue 15):

A Draize test was performed with two White rabbits, comparable to OECD guideline 405 (BASF AG 1971). Eyes were left unwashed after application of one sharp-edged spoon of the undiluted, solid test substance and were observed for 72 h. The mean score for conjunctivae redness was 0.16 in the treated eye, but was reversible within 72 h. In the control eyes, the mean conjunctivae redness score was also 0.16, reversible within 72 h. Scores for cornea, iris and chemosis were 0 at any reading time point in the treated eyes.

 

No irritating effects were also observed in a second study, comparable to OECD guideline 405 (Huntingdon Research Centre 1973, Val. 4). Eyes were left unwashed after application and were observed for 7 days. In 5/6 animals no findings were seen at any time point. The scores for Conjunctivae redness and chemosis were combined and expressed as one single value. One animal showed severe conjunctivae effects 24 hours after application of the test material. After 48 hours, the conjunctivae score was moderate. After 72 hours, no more findings were seen in this animal until the end of the observation period (7 days).

 

CAS No. 1328-53-6 (Pigment Green 7):

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.

 

CAS No. 574-93-6 (Pigment Blue 16):

No irritating effects were observed in a Draize test, comparable to OECD guideline 405 (BASF 1979). Eyes were left unwashed after application of ca. 100 mg of the undiluted, solid test substance and were observed for 8 days. No effects were observed in all 3 animals at any time point.

 

 

CAS No. 27614 -71 -7:

-No irritating effects were observed in a eye irritation test, acc. to OECD guideline 405 (Aventis Pharma 2001). Eyes were washed 24 h after application of ca. 100 mg of the undiluted, solid test substance and were observed for 72 hours after administration of the test material. One hour after administration the conjunctiva of one animal was very slightly swollen. Furthermore, all animals showed definitely injected blood vessels at one hour up to 48 h after administration. In addition to these observations, serous eye discharge discoloured by compound was noted. 72 h after administration, all signs of irritation had disappeared.

 

Justification for classification or non-classification

The available experimental test data on structural analogues are reliable and suitable for classification purposes under Regulation 1272/2008. In all 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 seventh time in Regulation (EC) No 2015/1221.