[2-(29H,31H-phthalocyaninylmethyl)-1H-isoindole-1,3(2H)-dionato(2-)-N29,N30,N31,N32]copper

Endpoint summary

Description of key information

The substance is an inert high molecular weight organic copper complex. Based on information on related substances, it is not systemically available after ingestion as indicated by lack of increased plasma and liver copper concentrations upon repeated oral dosing.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

The substance is an isomeric mixture of predominantly monosubstituted copper phthalocyanines. The monosubstituted isomers have a molecular weight of 735 g/mol and are described by the sum formula C41H21CuN9O2. Mass spectrometry shows the presence of higher substituted species up to n=6. The average degree of substitution is 1.4. Impurities are phthalimide, phthalic acid and phthalimidomethylphthalimide.

Toxicokinetic properties are assessed from experimental data on the copperphthalocyanine core (147-14-8) and an UVCB-analogue (CAS 59160-79-1) which consists of the identical components, but has a an average higher degree of substitution ( n = 2.48, range 0 - 3). It has the same impurities. The average mass is 970 g/mol. For data matrices and structures it is referred to the attachment with read-across justification.

The higher substituted analogue UVCB substance is insoluble in water as examined via total organic carbon and copper content (< 2 mg/L) and in octanol (< 1.57 mg/L). The copper phthalocyanine core has a measured water solubility of 0.009 mg/L and an octanol solubility of 0.0004 mg/L.

It is of higher molecular weight compared to the phthalocyanine core and has non-reactive substituents. Since systemic uptake depends on solubilities and size, the target substance is considered to be well-represented by the combination of data on the core and the higher alkylated analogue.

For both substances, the content of copper in in tissues was determined because copper ions are known to accumulate in liver; it can therefore serve as a biomarker for copper-containing substances.

Indeed, a similar 14 -day study with an acid-labile and lower molecular weight organic copper pigment (CAS 15680 -42 -9) showed that a gavage dosing for 14 days resulted in a significant increase in liver copper concentrations. For details it is referred to the dissiminated REACH-dossier of that substance.

For the analogue UVCB substance, a 14 -day study (originally intended as a dose-range-finder study) was performed with additional investigations on copper concentrations in liver and plasma at the end of treatment (BASF 2015). This study was performed with each 5 male and female rats per dose group and included clincal chemistry and haematology parameters. Oral dosing of up to 1000 mg/kg bw of

CAS 59160-79-1

did not cause increased copper concentrations in liver and plasma. No blue discoloration of internal tissues were observed. Clinical chemistry and haematology parameters were not affected and overall no adverse effects were noted. From this it is concluded that

CAS 59160-79-1

is not taken up by the body after ingestion. 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 (Batelle 1980). 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.

Considering the insolubility, the high molecular weight and the absence of copper accumulation observed for the core structure after 90 days and the higher subsituted UVCB-analogue after 14days it is concluded that the substance is not taken up after ingestion. Likewse, skin permeability is not expected.

Inhalation of dust is expected to result in local effects related to inert particles.