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

Endpoint summary

Description of key information

Repeated uptake of the phthalocyanine core and chlorinated derivatives did not cause treatment-related effects at the limit dose.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

4 500 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A category assessment is performed, which is based on the hypothesis that the copper phthalocyanine pigments are too insoluble in water or fat / octanol for systemic uptake. A data matrix and further information are provided in the chapter on toxicokinetic properties. The pigment is considered to show no adverse effects at the limit dose for the oral and dermal route. It is considered to behave like an inert dust upon inhalation.

Data on category members is summarized below:

CAS No. 147-14-8:

Valid experimental data were available to assess the toxicity of the tested material after repeated administration.

oral

A 28 day subacute study was conducted, according to the Japanese guideline for 28 Day Repeated Dose Toxicity Test of Chemicals with Wistar rats, which received 0, 40, 200 and 1000 mg/kg/day copper phthalocyanine by gavage (JETOC 1997). Food consumption and body weight were determined. The animal’s state of health was checked by cage side observations as well as by detailled clinical observations. Clinicochemical and hematological examinations were carried out at the end of the administration period and after a recovery period of 14 days. All animals were subjected to gross-pathological assessment, followed by histopathological examination. No changes in general condition, body weight gain or food consumption were detected in any of the groups. After the 28 days of administration, a slight, but significant decrease in red blood cell count (RBC) and decrease of hemoglobin (Hb) and packed cell volume (PCV) were detected in the 200 and 1000 mg/kg male groups. These slight changes were dose dependent. After the recovery period, a significant increase of erythroblasts was detected in the 1000 mg/kg female group. Increases of absolute organ weights of lung, spleen, adrenal and salivary gland and a tendency for increased relative organ weights of the spleen were evident in the 1000 mg/kg male group. No histopathological changes due to administration of phthalocyanine blue were detected.Therefore, a NOEL of 40 mg/kg bw per day was determined for male and female rats under the test conditions chosen. However, given the minor severity of the effects, their reversibility and the restricted relevance of the observations, a NOAEL of 1000 mg/kg bw may be attributed.

In two 90 day subchronic studies with F344 rats and B6C3F1 mice, comparable to OECD guideline 408, male and female animals received dose levels of 5.0, 2.5, 1.25, 0.6 and 0.3 % (w/w) copper phthalocyanine, administered in the food (approx. 0, 250, 500, 1100, 2200 and 4500 mg/kg bw for rats of both sexes, approx. 0, 1000, 2000, 4000, 8000 and 16000 mg/kg bw for male mice, and approx. 0, 1100, 2200, 4700, 9400 and 18700 mg/kg bw for female mice, calculated on average food consumption for 91 consecutive days (Batelle 1979). Animals were observed twice each day for clinical signs, with at least 6 hours between observations. All clinical signs were recorded daily. Gross examinations were performed on all animals from all dosage groups. Microscopic examinations were performed from kidney, liver, lung, heart, pancreas and pituitary from all animals in the control group and the highest dose treatment group. No clinical chemistry, hematology, or urinalysis were conducted and no organ weights were taken. No substance related mortality was reported for rats.There were seven early deaths for mice. Four male mice from four different dose or control groups and 3 control female mice died during the study. During the course of the 91-day study, neither treatment related signs of toxicity, nor abnormal clinical signs were observed in both rats and mice. Diet consumption among both male and female rats did not vary widely, nor showed any dose related trends. In mice, there were also no trends in diet consumption among dosed animals compared with controls in either male or female mice. No substance related changes were reported on macroscopic and histopathological examination of both rats and mice.

CAS No. 1328-53-6:

Valid experimental data were available to assess the toxicity of the tested material after repeated administration.

oral

A 28 day subacute study was conducted, according to the Japanese guideline for 28 Day Repeated Dose Toxicity Test of Chemicals with Wistar rats, which received 0, 100, 300 and 1000 mg/kg/day polychloro copper phthalocyanine by gavage (JETOC 1997). Food consumption and body weight were determined. The animal’s state of health was checked by cage side observations as well as by detailled clinical observations. Clinicochemical and hematological examinations as well as urinalysis were carried out at the end of the administration period and after a recovery period of 14 days.No deaths occurred in either sex. No effects ofpolychloro copper phthalocyaninewere detected in terms of general condition, body weights, food consumption, hematological or blood chemistry parameters, urinalysis, organ weights, or pathological examination in males or females.

In two 90 day subchronic studies with F344 rats and B6C3F1 mice, comparable to OECD guideline 408, male and female animals received dose levels of 5.0, 2.5, 1.25, 0.6 and 0.3 % (w/w) copper phthalocyanine, administered in the food (approx. 300, 600, 1200, 2300 and 4600 mg/kg bw for male rats, approx. 300, 600, 1250, 2500 and 5000 mg/kg bw for female rats as well as approx. 0, 1000, 2000, 4000, 8000 or 16000 mg/kg bw/day for male mice and approx. 0, 1200, 2500, 5000, 10000 and 20000 mg/kg bw/day for female mice, calculated on average food consumption, for 91 consecutive days (Batelle 1979).Animals were observed twice each day for clinical signs, with at least 6 hours between observations. All clinical signs were recorded daily. Gross examinations were performed on all animals from all dosage groups.Microscopic examinations were performed from kidney, liver, lung, heart, pancreas and pituitary from all animals in the control group and the highest dose treatment group. No clinical chemistry, hematology, or urinalysis were conducted and no organ weights were taken.

No substance related mortality was reported in rats, in mice 4 deaths occurred during the study which were not considered to be test substance related. No treatment related abnormal clinical signs were observed in either rats or mice. In mice, there were no trends in diet consumption among dosed animals compared with controls in either male or female mice. In rats there were slight trends in patterns of diet consumption between dosed and control rats of both sexes, with dosage groups eating about 1 g more of the higher concentrations of the dosed feed. In rats there were dose-related trends in body weights among both male and female rats, when body weights are expressed in percent differentials of weight gains compared with untreated controls. Male rats at the highest doses of 5.0 % and 2.5 % had differential weight gains of -11 % and -5 % respectively. Female rats at the top doses of 5.0 and 2.5 % had differential weight gains of -9.0 %. In mice, a -9 % to +8 % differential weight gain was seen in the dosed females. Animals in the highest dose levels had less weight gain than controls. Dosed male mouse groups showed a positive weight differential in all groups except the 0.6 % dosage group. In this group during week 12 with a corresponding weight loss was observed, which was not fully recovered during the final week of the study. However, given the normal variability in rodent body weight measurements, this differences did not necessarily reflect manifestation of toxicity. No substance related changes were reported on macroscopic and microscopic examination of the animals.

CAS 14832 -14 -5

Another 28 day subacute study was conducted, also according to the Japanese guideline for 28 Day Repeated Dose Toxicity Test of Chemicals with Wistar rats, which received 0, 100, 300 and 1000 mg/kg/day copper perchloro phthalocyanine by gavage (JETOC 1997). The animals were observed for clinical signs, body weights and food consumption; hematological and blood chemical examinations, urinalysis, and padiological examination were conducted. The tested material with the CAS number 14832-14-5 is equivalent to the CAS number 1328-53-6, as both CAS numbers are assigned to Polychloro copper phthalocyanine with the following distinction: CAS number 14832-14-5 (copper perchlorophthalocyanine) defines the maximal chlorinated phthalocyanine molecule (with a total of 16 chlorine atoms per molecule), whereas CAS number 1328-53-6 (polychloro copper phthalocyanine) defines a Polychloro copper phthalocyanine molecule with a variable content of 14 up to 16 chlorine atoms per molecule.No deaths occurred in either sex. No effects of copper perchloropolychloro phthalocyanine were detected in terms of general condition, body weights, food consumption, hematological or blood chemistry parameters, urinalysis, organ weights, or pathological examination in males or females.

An English translation of a Russian paper noted that polychlo copper phthalocyanine produced neither adverse clinical signs, nor any reduction in body weight gain occurred. Adverse liver and kidney effects were observed, but not specified. No further details were available (Kochanov 1966, Val. 4).

inhalation

Dose levels of 0.0, 9.7, 30 and 96 mg/m3 of the mixture Imron paint containing Desmodur N, containing polychloro copper phthalocyanine in unspecified quantity, was administered by inhalation (nose only) for two weeks to male rats. A NOAEL of 9.7 mg/m3 air was determined. However, as the tested material was a mixture; it is not equivalent to submission substance identity (Haskell 1987, Val. 3).

CAS No. 68987-63-3:

Valid experimental data were available to assess the toxicity of the tested material after repeated administration.

oral

A subacute study was conducted according to OECD 407 guideline with groups of five male and female CD rats receiving the test material orally by gavage at doses of 40, 200 and 1000 mg/kg bw/day for 30 days. A control group received vehicle alone. Further groups of each five males and five females were assigned to control and high dosage group and were treated for 30 days followed by a 16 day recovery period (Huntingdon 1997, Val. 1).

No animals died during the study. Blue staining of the coat and/or tail occured in one male and one female receiving 200 mg/kg bw/day and in all animals receiving 1000 mg/kg bw/day. Bodyweights, food consumption and food conversion efficiency were unaffected by treatment. Haematoglogical examination on day 30 revealed no treatment-related changes. Biochemical examination of the plasma on day 30 revealed slightly increased urea concentrations in males receiving 200 or 1000 mg/kg bw/day, but full recovery was apparent. The composition of the urine was unaffected by treatment. Liver and ovary weights were higher than controls after 30 days in females receiving 200 or 1000 mg/kg bw/day and testes weights were higher than in controls in males receiving 1000 mg/kg bw/day. These differences were fully reversible. Abnormal contents (dark, blue or green) of the gastro-intestinal tract were seen after 30 days in 2 males and in one female, receiving 1000 mg/kg bw/day. There were no microscopic findings that were related to treatment with the test material.

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

The available studies are considered reliable and suitable for classification purposes under 67/548/EEC. No serious irreversible effects were observed at dose levels of less than 150 mg/kg bw upon subacute exposure. As a result the substance is not considered to be classified for repeated dose toxicity under Directive 67/548/EEC, as amended for the 31st time in Directive2009/2/EG.

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. There were no significant toxic effects at doses of less than 300 mg/kg bw upon subacute oral exposure in rats. As a result the substance is not classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the fifth time in Directive EC944/2013.