[N,N,N',N',N'',N''-hexaethyl-29H,31H-phthalocyaninetrimethylaminato(2-)-N29,N30,N31,N32]copper

Endpoint summary

Description of key information

Based on its physico-chemical characteristics, CAS number 28654-73-1 is considered to be characterised by low or no bioavailability via the oral or dermal route of exposure. Absorption after inhalation exposure is not expected. A distribution through extracellular body fluids as well as the formation of reactive metabolites are considered unlikely. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

In line with chapter R.7 c (ECHA, 2012) the main toxicokinetic properties of CAS number 75247-18-6 are assessed on the basis of its physico-chemical properties and with special regard to the results of the standard toxicity studies performed with this substance. Specific toxicokinetics or dermal absorption studies are not available for the substance.

 

The substance(CAS 28654-73-1 is the base contained in[N, N, N', N', N'', N''-hexaethyl-29H,31H-phthalocyaninetrimethylaminato(2-) -N2 9, N30, N31, N32]copper tris(dodecylbenzenesulphonate) (CAS 75247-18-6). Another similar compound is CAS 81457-65-0. A data matrix is given below:

 

	[N, N, N', N', N'', N''-hexaethyl-29H,31H-phthalocyaninetrimethylaminato(2-) -N2 9, N30, N31, N32]copper	[N, N, N', N', N'', N''-hexaethyl-29H,31H-phthalocyaninetrimethylaminato(2-) -N2 9, N30, N31, N32]copper tris(dodecylbenzenesulphonate)	Copper, [29H,31H-phthalocyaninato(2-) -N29, N30, N31, N32]-, [[3-(1-methylethoxy) propyl]amino]sulfonyl derivs.
CAS number	28654-73-1	75247-18-6	81457-65-0
Molecular weight:	831.5 g/mol	1426.95 g/mol	1293 g/mol
Physical state:	solid (blue powder)	solid (blue powder)	solid (blue powder)
logPow:	0.6	Not applicable (surface activity)	Not tested due to low water solubility
Water solubility:	< 0.02 mg/L (at 20 °C)	Insoluble*	< 0.18 mg/l at 20 °C
Octanol solubilty	21.4 mg/L	Dispersible at ca 3 g/L	2.4 g/L
Vapour pressure:	<0.0001 Pa (at 20 °C)	Not determined as substance decomposes prior to melting above 250°C	Not determined as substance decomposes prior to melting above 216°C
Oral LD50, rat	> 10000 mg/kg bw	> 10000 mg/kg bw	> 10000 mg/kg bw
Inhalation LC50
Intraperitoneal LD50, mouse	> 10000 mg/kg bw	1400 mg/kg bw
DermalLD50, rat	> 2500 mg/kg bw
Skin irritation	Not irritating	Not irritating	Not irritating
Eye irritation	Not irritating	Not Irritating	Not Irritating
Skin sensitisation (OECD 429, LLNA)	Sensitizing (GHS Cat 1B, EC3= 18%)	Non sensitizing	Non sensitizing
NOAEL (oral, 46 days, rat) (OECD 422)		1000 mg/kg bw/day	1000 mg/kg bw/day
Bacterial reverse mutation assay (Ames-test)	Non mutagenic	Non mutagenic	Non mutagenic
In vitromammalian cell gene mutation assay (HPRT)		Non mutagenic	Non mutagenic
In vivomicronucleus assay			Non genotoxic
NOAEL (oral, 46 days, rat)		1000 mg/kg bw/day	1000 mg/kg bw/day

*The anion in the substance is tris(dodecylbenzenesulphonate(DBS, CAS 27176-87-0 )which is surface active and to some extent dispersible/soluble in water.

According to the OECD SIDS (2007) on long chain alkyl sulfonates, the experimental aqueous solubility and log KOW for the sodium salt have been determined to be 300 mg/L and 1.96, respectively.

The cation is a modified copper phthalocyanine with short side chains ending in an ammonium ion. The water solubility of the amine (CAS 28654-73-1) was determined experimentally to be less than 0.02 mg/L.

In aqueous media that do not trigger in dissociation of the anion and cation, the solubility in water is equally low.

 

 

 

Absorption:

Based on its high molecular weight of 831 g/mol CAS number 28654-73-1 is not likely to be quantitatively absorbed in the GI tract since large molecules with a molecular weight above 1000 g/mol do not favor absorption. This assumption is supported by the results of the acute studies with the substance itself and and the repeated dose oral toxicity study with the dispersible salt (BASF SE 2013, according to OECD 422) indicating no signs of systemic toxicity except diarrhea after exposure to the test substance. Following repeated exposure up to limit doses, blue discoloration was found in the feces and the lumen of the intestinal tract but not in other organs or tissues including the lymphatic system pointing out that the blue test item was not able to pass the intestinal wall in toxicologically relevant amounts. The dispersible form was chosen for testing, because it can be dispersed in octanol at high concentrations. This property was expected to make the dispersible form more likely for systemic uptake and transport than the poorly soluble base.

In addition, the dispersible salt (CAS 75247-18-6) is of higher molecular weight, but significantly more toxic upon intraperitoneal injection. Whereas no toxicity was observed after a single injection of 10 000 mg/kg bw for the substance, itself, the disperlible salt caused mortality with an LD50 of 1470 mg/kg bw (BASF AG 1973). In that study acute delayed toxicity was observed upon a single intraperitonal injection of 1470, 2150 and 3160 mg/kg bw (BASF AG 1973). The substance was applied in an aqueous suspension with 0.5% carboxymethylcellulose. All animals of the mid and high dose groups died within 14 and 7 days, respectively. Mortality also occurred at the low dose group which was identified as the LD50. Necropsy showed intraabdominal substance deposition and sporadic agglutinations. In case of significant uptake of the substance, systemic toxicity should have been observed during the subacute oral toxicity study. This was however not observed.

No information is available on whether the dispersible form is dissociated into cation and anions in the acidic environment of the stomach. The cation is also a blue colorant of high molecular weight (831 g/mol). In its neutral form, it is poorly soluble in water and of low solubility in octanol. Should the cation become protonated in the stomach acid, it is expected to be of slightly better solubility. Large particles and molecules may be transported cross the biological membranes of the GI tract into the epithelial cells by phagocytosis. However the amount of substances taken up via this route of absorption is very limited.

Absorption of surfactants may be enhanced because of damage to the cell membranes. The surface tension of CAS number 75247-18-6 was determined according to OECD 115 (BASF SE, 2009) by preparing a solution in distilled water using a 90% saturation concentration. Within this study a surface tension of 53.7 mN/m (20°C) was determined indicating slight surface activity. An enhanced absorption to cell membranes cannot be excluded but was not apparent from organ coloration or systemic toxicity.

The substance is not volatile and inhalation to vapors is not relevant. Exposure to dust needs to be avoided as the substance is expected to behave like an inert dust. Experimental data is not available.

No experimental data is available on repeated dermal exposure. Based on the molecular weight of > 500 g/mol, insolubility in water and absence irritating properties, skin permeability is expected to be very poor. The substance showed a moderate potential for skin sensitization in the local lymph node assay (OECD 429, BASF 2011). The substance was applied as a suspension due to overall poor solubility. The effective concentration was very high (EC3 = 18%) indicating that the sensitizing properties might be related to a by-product rather than the substance itself. No indication of skin permeability such as urine or faeces discoloration was observed in the LLNA.

Distribution/Metabolism:

Since no clinical signs were observed in acute oral, dermal and inhalation toxicity studies a distribution to potential target organs seems unlikely. Even through there was no indication based on macroscopic and histopathology examinations following repeated oral exposure with the dispersible form, a distribution by the lymphatic system cannot be ruled out. As the substance is of low solubility in octanol, transport via chylomicrons could in theory occur. However, no evidence in form of blue discoloration was seen in the available studies.

Generally, metabolism will render a xenobiotic molecule more polar and harmless, leading to fast and quantitative excretion. For the test item, no conversion into a metabolite that was more cytotoxic or more genotoxic than the parent substance was noted when comparing in vitro test results with metabolic activation to in vitro test results without metabolic activation system (genetic toxicity tests). Similar results were obtained for a structural analogue (CAS no. 81457 -65 -0) in a mammalian erythrocyte micronucleus test in vivo (Ciba Geigy Ltd., 1982), where no evidence of mutagenicity effects was observed in Chinese hamsters.

Excretion:

In the acute and repeated dose oral toxicity studies in rats (BASF AG, 1976, similar to OECD Guideline 401; BASF SE 2013, according to OECD 422) blue discoloration, originating from the test item, was found in the lumen of the intestinal tract and in the feces but not in any other organ or tissue. The results lead to the conclusion that a direct excretion via the feces without former GI tract absorption of the test substance represents the main excretion route after oral exposure.