[2,9,16,23-tetrachloro-29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]copper

Endpoint summary

Description of key information

Experimental data on copper phthalocyanine pigments suggests lack of absorption after ingestion or skin contact. The pigments are considered to behave like inert dust upon inhalation.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

A category assessment of the copperphthalocyanine-based pigments is performed. A data matrix with physico-chemical properties, identifiers and toxicological data is shown below. The chemical structures are provided in the attachment.

The basic copper phthalocyanine has a very low solubility in water (0.009 mg/L) and in octanol (0.0004 mg/L). Chlorination or bromination introduces non-polar atoms so that the solubility is not altered in a manner that is favourable to systemic uptake.

The pigments do not contain functional groups that are susceptible to pH dependent hydrolysis at environmentally relevant pH or stomach acid. Their relative density is between 1.4 and 3.1 and none of them melt at temperatures below 400°C.

 

 Experimental data regarding toxicokinetic properties is available for two substances. It involves examination of the tissue copper content at the end of subchronic feeding studies with the basic copperpththalocyanine (CAS 147-14-8) and its chlorinated UVCB-version (CAS 1328-53-6). Copper is known to accumulate in the liver, but subchronic exposure did not show a significant increase in the liver copper concentration. Both studies were performed as part of the US National Toxicology program. The evaluators of the studies judged the very slight increase in copper concentrations as caused by soluble copper by-products and as being no indication of systemic availability of the copper phthalocyanine core.

This is supported by the lack of any adverse effects observed in long-term or short-term studies.

Even intraperitonale injection (single dosing) did not result in adverse effects.

The most thorougly investigated substance is that with lowest molecular weight, but subacute oral data is also available for chlorinated derivates. Therefore, the avaialble data set is considered adequate for the whole category.

It is also consistent with the general knowledge on the hazard profile of organic or organo-metallic pigments that has been accumulated during the last years of REACH.

 

 

The molecular weight of each category member is well above the threshold of 500 g/mol which is given in the EU guidance document on dermal absorption (Sanco/222/2000 rev. 7, March 19, 2004). This threshold allows the assumption of 10% dermal permeation if the n-octanol/water partition coefficient is either very low (-1) or high (> 4). The threshold for log Pow is not reached for every member, but this is due to the overall very poor solubility of the pigments. Solubility is in the lowmg/L range which is hindering any transport process.

None of the available data indicates that the pigments cause skin irritation which would damage the dermal barrier. As discussed in the toxicokinetic section, absence of systemic uptake after ingestion postulated.

 A valid study for acute dermal toxicity in rabbits is available for the basic copper phthalocyaninen which has a molecular weight of 576 and a log Pow of -1 (based on measured solubilities in octanol and water) . No indication of adverse effects was observed.

Based on the lack of uptake after ingestion and the physico-chemical properties, lack of dermal penetration is postulated.

 

Regarding the inhalation route, the pigments are considered to have the properties of an inert dust.

Details on the studies on absorption after ingestion is provided below:

CAS No. 147-14-8

There are valid experimental data available to assess relevant toxikokinetic (distribution) informations of copper phthalocyanine. Concentrations of copper phthalocyanine were analyzed in liver and kidney of male rats and mice after oral exposure in a subchronic 90-day feeding study. The concentrations were 0.3 %, 0.6 %, 1.25 %, 2.5 % and 5 % in the diet for rats (corresponding to approx. 0, 250, 500, 1100, 2200 and 4500 mg/kg bw for both sexes [based on 16.4 g/d average food consumption, 0.182 kg average bw for males and on 11.55 g/d average food consumption, 0.130 kg average bw] for females) and mice (approx. 0, 1000, 2000, 4000, 8000 and 16000 mg/kg bw for males [based on 7.3 g/d average food consumption, 0.023 kg average bw] and approx. 0, 1100, 2200, 4700, 9400 and 18700 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively), administered on 90 consecutive days. The liver and kidney tissues from the highest dose and from controls of male animals were dissolved in nitric acid and subsequently analyzed for copper by atomic absorption spectrophotometry. No statistically significant increases of copper incorporation were reported in the liver (2.82 ppm +- 0.34 ppm vs. 2.78 ppm +- 0.51 ppm) and kidney (5.62 ppm +- 0.49 ppm vs. 5.30 ppm +- 0.83 ppm) tissues of treated male rats of the highest dose group, compared to control animals. Therefore, the authors strongly suggested that the test material was not absorbed under the test conditions chosen. Slight, but statistically significant increases of copper incorporation were reported in the liver (3.98 ppm +- 1.16 ppm vs. 3.0 ppm +- 0.34 ppm) and kidney (7.47 ppm +- 2.86 ppm vs. 4.66 ppm +- 0.6 ppm) tissues of treated male mice, compared to control animals (Batelle 76-34-106002).

Another study with partially limited reliability (Val. 4) provided information on the copper content in the blood serum of rats, determined by the atomic-absorption method. The authorsof the study reported the following: No test material or products of its metabolism were detected in the blood of the animals. An increased Cu2+ content in the serum was connected to the content of soluble copper salts in the pigment. Treatment with purified test material did not alter the Cu2+ concentration in the serum of the animals.

 

CAS No. 1328-53-6

There are valid experimental data available to assess relevant toxikokinetic (distribution) informations of polychloro copper phthalocyanine. Concentrations of polychloro copper phthalocyanine were analyzed in liver and kidney of male rats and mice after oral exposure in a subchronic 90-day feeding study. The concentrations were 0.3 %, 0.6 %, 1.25 %, 2.5 % and 5 % in the diet for rats (corresponding to approx. 0, 250, 500, 1100, 2200 and 4500 mg/kg bw for both sexes [based on 16.4 g/d average food consumption, 0.182 kg average bw for males and on 11.55 g/d average food consumption, 0.130 kg average bw] for females) and mice (approx. 0, 1000, 2000, 4000, 8000 and 16000 mg/kg bw for males [based on 7.3 g/d average food consumption, 0.023 kg average bw] and approx. 0, 1100, 2200, 4700, 9400 and 18700 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively), administered on 90 consecutive days. The liver and kidney tissues from the highest dose and from controls were dissolved in nitric acid and subsequently analyzed for copper by atomic absorption spectrophotometry. Polychloro copper phthalocyanine produced slight, but statistically significant increases in the copper levels in rat liver (4.28 +- 1.1 vs. 3.08 +- 0.39 ppm) and kidney (8.23 +- 1.75 vs. 4.68 +- 0.82 ppm) as well as in mouse kidney (6.57 +- 1.9 vs. 4.04 +- 0.8 ppm). Copper levels in mouse liver were not altered.

Within the framework of an expert judgement, the evaluating author strongly suggested that the test material was not appreciably absorbed under the test conditions chosen with the following justification: The reported minor changes in tissue levels indicate a small exposure of the organs to copper. Changes were always less than two fold. Absorption of the substance by the gastrointestinal tract is considered to be unlikely since polychloro copper phthalocyanine is of high molecular weight, insoluble in aqueous media and chemically inert. This suggests that free copper, present as a minor impurity in the pigment, is responsible for the slight increases in tissue copper levels that were noted (Assessment from Dr. Mennear JH, Expert Toxicologist to Dr. Moore JA, Deputy Director NTP).

Overall, the following substances are covered:

Pigment Blue 15                              

CAS 147-14-8         

[29H,31H-phthalocyaninato(2-)-kappa~2~N~29~,N~31~]copper

           

C.I. Pigment Green 7                    

1328-53-6    

29H,31H-phthalocyaninato(2-)-kappa~2~N~29~,N~31~]copper,chlorinated

 

CAS 12239-87-1    

Copper, [C-chloro-29H,31H-phthalocyaninato(2.kappa.N29,.kappa.N30,.kappa.N31,. kappa.N32]-  

           

C.I. Pigment Green 36                  

CAS 68512-13-0    

[29H,31H-phthalocyaninato(2-)-kappa-2N-29~,N-31~]copper,brominatedchlorinated                                

           

C.I. Pigment Green 36                  

CAS 14302-13-7    

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

 

CAS 16040-69-0    

[2,9,16,23-tetrachloro-29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]copper                     

 

CAS 27614-71-7    

[29H,31H-phthalocyaninato(2-)-.kappa.N29,.kappa.N30,.kappa.N31,.kappa.N32]copper,tetrachlorinated    

           

C.I. Pigment Green           7                    

CAS 68987-63-3  

[29H,31H-phthalocyaninato(2-).kappa.N29,.kappa.N30,.kappa.N31,.kappa.N32] copper,chlorinated                      

 

 

C.I. Pigment Blue 16                     

CAS 574-93-6         

29H,31H-phthalocyanine

Table A: Physico-chemical proprties

	[29H,31H-phthalocyaninato(2-)-kappa~2~N~29~,N~31~]copper	29H,31H-phthalocyaninato(2-)-kappa~2~N~29~,N~31~]copper,chlorinated	Copper, [C-chloro-29H,31H-phthalocyaninato(2.kappa.N29,.kappa.N30,.kappa.N31,. kappa.N32]-	[29H,31H-phthalocyaninato(2-)-kappa-2N-29~,N-31~]copper,brominatedchlorinated	29H,31H-phthalocyanine	1,3,8,16,18,24-hexabromo-2,4,9,10,11,15,17,22,23,25-decachloro-29H,31H-phthalocyaninato(2-)-kappa~2~N~29~,N~31~]copper	[2,9,16,23-tetrachloro-29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]copper	[29H,31H-phthalocyaninato(2-)-.kappa.N29,.kappa.N30,.kappa.N31,.kappa.N32]copper,tetrachlorinated	[29H,31H-phthalocyaninato(2-).kappa.N29,.kappa.N30,.kappa.N31,.kappa.N32] copper,chlorinated
	147-14-8	1328-53-6	12239-87-1	68512-13-0	574-93-6	14302-13-7	16040-69-0	27614-71-7	68987-63-3
Mol. weight	576	>= 644.0 — <= 1120.0	610.541	>= 689.0 - 1394.0	515	1'393.896	713.84	>= 576.0 — <= 1120.0	>= 610.0 — <= 1120.0
Melting point	480°C	>400°C			>400°C	480°C		Decomposition at 470°C
Relative densitiy	1.62	2.14			1.442	3.01		1.726
Water solubility (μg /L)	9 mg/L	1-3 µg/L	< 0,1 mg/L	< 1 mg/L	<0.001 μg/L (calculated)	< 0,1 mg/L		< 10 μg/l	l
n-octanol solubility (μg /L)	0.4mg/L
Log Pow  (calculated from solubilities)	-0.88 to -1.39

Table B: Toxicological data

CAS	147-14-8	1328-53-6	12239-87-1	68512-13-0	574-93-6	14302-13-7	16040-69-0	27614-71-7	68987-63-3
Acute oral toxicity (LD50, mg/kg bw)	LD50> 5000  in rat K2	LD50> 5000 in rat K2			LD50> 5000 in rat K2	LD50 > 16000 in mice K2		LD50> 2000 in rat K1
Acute inhalation toxicity (LD50)
Acute dermal toxicity (LD50)	LD50> 2000 K1
Acute intraperitoneal toxicity (LD50, mouse)		LD50> 2000 K2			LD50> 2000 K2
Skin and eye irritation in rabbit	Not irritating K2	Not irritating K2			Not irritating K2			Not irritating K2
Skin sensitization	Not sensitizing (LLNA, GPMT) K1							Not sensitizing (LLNA) K1
Reproductive toxicity screening study (OECD 421) gavage	NOEL = 1000 mg/kg (K1)
Subacute oral toxiicty (OECD 407)	NOAEL = 1000 mg/kg (K1)	NOEL = 1000 mg/kg (K1)							NOEL = 1000 mg/kg (K1)
Bacterial mutagenicity	Non mutagenic (4 strains) K2	Non mutagenic K1	Non mutagenic ( 4 strains) K2		Non mutagenic  K1	Non mutagenic  K1		Non mutagenic  K1	Non mutagenic  K1
Clastogenicity in vitro	Non clastogenic K2	Non clastogenic (OECD 473) K2   Non clastogenic (MN in vitro) K1							Non clastogenic K1
Mutagenicity in mammalian cells in vitro	Non mutagenic UDS in vitro K1   Non mutagenic MLA, K4   Mutagenic in MLA (Crude material)
Clastogenicity in vivo (MN)	Non genotoxic K2
Mouse Spot test	Non genotoxic K2
Subchronic or chronic toxicity in rats (feed)	NOAEL: ca. 4500 mg/kg /5% in the diet, K2
Subchronic or chronic toxicity in mice (feed)	NOAEL: ca. 16000 mg/kg /5% in the diet, K2
Toxicity to reproduction
carcinogenicity