Brominated chlorinated copper, [29H,31H-phthalocyaninato(2-)-N29,N30,N31,N32]-, wherein the number of bromines is equal to or more than 10 and less than 16, and the number of chlorines is equal to or more than 0 and less than 7

Endpoint summary

Description of key information

The substance is non hazardous as assessed by read-across.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Species:

rat

Dose descriptor:

NOAEL

Effect level:

>= 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of adverse findings at the limit dose

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 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

 

Repeated dose oral toxicity has been studied in two subchronic feeding studies each in mice and rats with Pigment Blue 15 and Pigment Green 7. Subacute GLP-compliant gavage studies were performed with Pigment Blue 15, Pigment Green 7, CAS 14832-14-5 and CAS 68987-63-3. All studies consistently show absence of adverse effects at the limit dose.

Further information on read-across is given in the attachment of the endpoint study record.

CAS No. 147-14-8 (Pigment Blue 15):

A GLP-compliant 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 1995). The test material is described to be of technical grade. Food consumption and body weight were determined. The animal’s state of health was checked by cage side observations as well as by detailed 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, but within the normal variation range. After the recovery period, a significant increase of erythroblasts was detected in the 1000 mg/kg female group. Also after the recovery period, slight 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 in comparison to the control group. These differences were of statistical, but not of biological relevance. No histopathological changes due to administration of phthalocyanine blue were detected. Therefore, a NOAEL of 1000 mg/kg bw per day was determined for male and female rats under the test conditions chosen.

 

 

In two 90 day subchronic feeding studies with F344 rats and B6C3F1 mice, 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.

This study was originally performed to serve as a range-finder for a chronic feeding study. It included determination of copper levels in kidneys and livers to find out if there was indication of uptake after ingestions. Since there was no significant increase in copper concentration, Pigment Blue 16 was considered to be inert and not absorbed, and the chronic toxicity study was not performed.

 

 

 

 

 

CAS No. 1328-53-6 (Pigment Green 7):

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

oral

A GLP-compliant 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 using corn oil as vehicle (MHLW 2000). Food consumption and body weight were determined. The animal’s state of health was checked by cage side observations as well as by detailed 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 of polychloro copper 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.

 

In two 90 day subchronic studies with F344 rats and B6C3F1 mice, 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 No. 14832-53-6

A GLP-compliant 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, 20, 140 and 1000 mg/kg/day copper perchloro phthalocyanine by gavage using olive oil as vehicle (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. 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.

 

CAS No. 68987-63-3

A GLP-compliant 28 day subacute study was conducted following OECD guideline 407 (Huntington Life Sciences 1997). Oral administration at dosages of 40, 200 and 1000 mg/kg/day in corn oil was generally well tolerated. No target organ was identified.

The blue staining seen in the intermediate and high dosage groups, and the abnormal contents of the gastro-intestinal tract in high dosage animals were considered to be due to the test material, since it was a blue colour, and was therefore of no toxicological significance. The NOAEL was determined to be 1000 mg/kg bw.

 

A few old literature publications mentioned in the OECD SIDS document were not included in the REACH registration dossier since they contained little information and also in some cases it was found that the test items were indeed not pigments but soluble dyes.

 

 

 

Repeated dose inhalation toxicity

Repeated dose inhalation toxicity was not performed as the substances are inert poorly soluble particles when manufactured as powder. They are non volatile and not inhalable if imbedded in a matrix such as a coating, a plastic article or a suspension.

A 5-day inhalation study with three-week recovery was performed with Pigment Blue 16 (BASF 2016). This study examined both systemic and local effects. The NOAEC was determined to be the highest tested dose of 30 mg/m³.

 

Repeated dose dermal toxicity

No studies on repeated dose dermal toxicity are available. The molecular weights of the copper phthalocyanine pigments is greater than 500 g/mol which in combination with poor solubility is an indication of low skin permeability. Considering that no hazard was identified at the limit dose for the oral route, there is no concern for a hazard via the dermal route. Testing for the dermal route is not needed.

 

Justification for classification or non-classification

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 tenth time in Regulation (EU) No 2017/776.