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Administrative data

Link to relevant study record(s)

Description of key information


In summary, copperphthalocyanine-based pigments are not absorbed after ingestion and after skin contact. Upon inhalation, inhalable forms of the pigment are considered to behave like in inert particles.

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 of the chemical safety report.


In summary, CAS 1328-53-6 is not absorbed after ingestion and after skin contact. Upon inhalation, inhalable forms of the pigment are considered to behave like in inert particles.


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 polychlorinated 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 (see data matrix).


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


The most thorougly investigated substances are those with lowest molecular weight (unsubstituted copper phthalycanine, Pigment Blue 15) and the polychloro copper pththalocanine (Pigment Green 7), 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.


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



574-93-6



147-14-8



12239-87-1



16040-69-0



27614-71-7



 


 68987-63-3



1328-53-6



14832-14-5



68512-13-0



14302-13-7



 



29H,31H-phthalocyanine


 


No Copper



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


 



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



[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  


 



Copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32,chlorinated



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



Hexadecachlorinated CuPC



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



[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               



Type and number of substituents


(16 = completely substituted)



none



none



Cl =1



Cl = 4



Cl = 4



Cl = undefined



Cl = 14 - 16



Cl = 16



Cl+Br = 16



Br = 6


Cl = 10



Test material purity



 



95-99%



 



 



>85%%



99%



94-100%



99%



 



>99%


 



Colour Index name



Pigment Blue 16



Pigment Blue 15



-



-



-



-



Pigment Green 7



-



-



Pigment Green 36



Molecular weight (g/mol)



515



576



611



714



576 —1120



610 —1120



1057 - 1127



1127



689 - 1394



1394



Octanol solubility



 



0.4mg/L



 



 



 



 



0.4mg/L



 



 



 



Water solubility



<0.001 μg/L (calculated)



9mg/L



 



 



< 10 μg/l



 



1-3 µg/L



 



 



 



Relative density



1.442



1.62



 



 



1.726



 



 2.1



 



 



3.01



Acute oral toxicity (LD50, mg/kg bw)



LD50> 5000


 in rat


K2


 


No mortality



LD50> 5000


 in rat


K2


 


No mortality



 



 



LD50> 2000


in rat


K1


 


No mortality



 



LD50> 5000


in rat


K2


 


No mortality



 



LD50> 5000


in rat


K2


 


LD50> 10000


in rat


K2


 


No mortality


 



LD50 > 16000


in mice


K2


 


No mortality, purity not specified, but not relevant as excessive dose tested.



Acute dermal toxicity (LD50, mg/kg bw)



 



LD50> 2000


K1


 


No mortality



 



 



 



 



 



 



 



 



Acute intraperitoneal toxicity (LD50, mg/kg bw mouse)



LD50>2000


K2


 


No mortality



LD50> 3000


K4


 


No mortality



 



 



 



 



LD50> 2000


K2


 


No mortality



 



 



 



Skin and eye irritation in rabbit



Not irritating


K2



Not irritating


K2



 



 



Not skin irritating


K1



 



Not irritating


K2



 



Not irritating


K2



 



Skin sensitization



 



Not sensitizing (LLNA, GPMT) K1



 



 



Not sensitizing


(LLNA)


K1



 



Not sensitizing (LLNA)


K1



 



 



 



Reproductive toxicity



 



NOEL = 1000


mg/kg


(OECD 421)


K1


 


Waiver for 2-Gen and Dev Tox



 



 



 



 



 



 



 



 



Subacute oral toxicity (OECD 407)


 



 



NOAEL = 1000 mg/kg


K1



 



 



 



NOAEL = 1000 mg/kg bw


K1



 


NOAEL = 1000 mg/kg bw


K1


 

NOEL = 1000


mg/kg


K1



 



 



5-day short-term inhalation study with 3-week-recovery



 



NOAEC = 30 mg/m3


K1



 



 



 



 



 



 



 



 



14-day inhalation study



 



 



 



 



 



 



[NOEC = 9.7 mg/m3]


K3, unspecified test substance


 Imron paint & Desmodur N-100 (mixture of various compounds, including CAS No 1328-53-6 in unspec. quantity)



 



 



 



Bacterial mutagenicity



Non mutagenic


 K1



Non mutagenic


(4 strains)


K2



 



 



Non mutagenic


 K1



Non mutagenic


K1



Non mutagenic


K1


 



Non mutagenic


K1


 



Not mutagenic


K1


(three samples with different Br-substitution grades tested)



Non mutagenic


 K1



Clastogenicity in vitro



 



Non clastogenic


(OECD 473)


K1



 



 



 



Non clastogenic


(OECD 473)


K1



 


Non clastogenic (OECD 473)


K1


 


Non clastogenic (MN in vitro)


K1



Non clastogenic (OECD 473)


K1


 



 



 



Mutagenicity in mammalian cells in vitro



 study ongoing



Non mutagenic


UDS in vitro K1


 


Non mutagenic MLA, K4


 



 



 



 



 



Non mutagenic


UDS in vitro


K4


 



 



 



 



Clastogenicity in vivo (MN)



 



Non genotoxic


K2


(crude material)



 



 



 



 



 



 



 



 



Mouse Spot test



 



Non genotoxic


K2


(crude material)



 



 



 



 



 



 



 



 



Subchronic toxicity in rats


(feed)



 



NOAEL: ca. 4500 mg/kg = 5% in the diet


K2



 



 



 



 



NOAEL: ca. 4500 mg/kg = 5% in the diet


K2


 



 



 



 



Subchronic toxicity in mice


(feed)



 



NOAEL: ca. 16000 mg/kg = 5% in the diet


K2



 



 



 



 



NOAEL: ca. 16000 mg/kg = 5% in the diet


K2


 



 



 



 



Toxicokinetic information



 



No statistically significant increases in copper incorporation was reported in the liver and kidney of male animals after 90 day feeding with 5% in the diet*



 



 



 



 



No statistically significant increases in copper incorporation was reported in the liver and kidney of male animals after 90 day feeding with 5% in the diet**



 



 



 



 


*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).


 


 


**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).


 


Regarding particle properties, the following is available:


The dispersion stability of Pigment Green 7 was depended on pH and water hardness. Dissolution was excluded as the main cause of the apparent stability. At pH 7 and 9 in 1 mM Ca and for all samples in 0 mM Ca the stability was low.


 


Important publications including information on Pigment Green 7 are:


 


Arts et al 2016


Case studies putting the decision-making framework for the grouping and testing of nanomaterials (DF4nanoGrouping) into practice


Regulatory Toxicology and Pharmacology 76 (2016) 234e261


 


Koltermann-Juelly 2018


Abiotic dissolution rates of 24 (nano)forms of 6 substances compared to macrophage-assisted dissolution and in vivo pulmonary clearance: Grouping
by biodissolution and transformation


NanoImpact 12 (2018) 29–41


 


Wohlleben et al 2019


The nanoGRAVUR framework to group (nano) materials for their occupational, consumer,
environmental risks based on a harmonized set of material properties, applied to 34 case studies. Nanoscale, 2019, 11, 17637


 


Stratmann et al 2020


Indicators for lack of systemic availability of organic pigments


Regulatory Toxicology and Pharmacology 115 (2020) 104719