Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 261-638-5 | CAS number: 59160-79-1
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Link to relevant study record(s)
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: non GLP, but well documented.
- Reason / purpose for cross-reference:
- reference to same study
- Objective of study:
- other: distribution in plasma and liver
- Principles of method if other than guideline:
- Copper-content was determined in plasma and liver samples of rats that had been given gavage doses for 14 days at doses of 300 and 1000 mg/kg bw.
- GLP compliance:
- no
- Specific details on test material used for the study:
- Purity >= 97%
Batch no. 120001P040
Date of production: 13 March 2012
stability: unlimited
homogenity: given
appearance: solid, blue
storage conditions: ambient (room temperature); dry storage; protect against humidity - Radiolabelling:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sulzfeld, Germany
- Age at study initiation: 42 +/- 1 days
- Weight at study initiation:
- Fasting period before study: none
- Housing: single
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least five days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30 - 70%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 2014-06-09 To:2014-06-24 - Route of administration:
- oral: gavage
- Vehicle:
- other: dnnkmg water containing 0.5% carboxymethylcellulose with about 5 mg/100 ml Cremophor EL
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Daily
The substance is a homogenous suspension. - Duration and frequency of treatment / exposure:
- 14 days
- Dose / conc.:
- 300 mg/kg bw (total dose)
- Dose / conc.:
- 1 000 mg/kg bw (total dose)
- No. of animals per sex per dose / concentration:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control reference chemical:
- A 14-day gavage study with an acid-labile copper-pigment (CAS 15680-42-9) was performed in the same year and this study showed a strong increase in liver copper content. (Plasma concentrations were not determined.)
- Details on study design:
- see endpoint study record for repeated dose toxcity
- Details on dosing and sampling:
- The determination of copper concentrations in EDTA plasma samples after were performed at the test facility.
The total concentrations of the test substance in plasma were calculated indirectly from the determined copper concentrations (inductively-coupled-plasma mass-spectrometry; experimental error + /- 0,2 mg/kg Cu).
This part of the study was carried out in compliance with the Principles of Good Laboratory Practice.
On study day 15, EDTA blood samples (about 200 μL) were collected from fasted animals by puncturing the retro-bulbar venous plexus under isoflurane anesthesia. After plasma preparation, the samples were frozen at about -80°C prior to analysis.
Liver samples were frozen at about -80°C prior to analysis. - Type:
- distribution
- Results:
- No increase in plasma and liver copper concentration was detected.
- Details on distribution in tissues:
- No increase in plasma and liver copper concentration was detected (see tables 1 and 2).
- Conclusions:
- Interpretation of results: no bioaccumulation potential based on study results
- Executive summary:
Table 1: Copper content in liver samples
animal no. g liver mg Copper mg/g liver mean (n = 5) 1 2.043 0.011 5.38 5.54 males 2 2.021 0.011 5.44 control 3 2.2772 0.013 5.71 4 1.9791 0.012 6.06 5 1.9656 0.01 5.09 6 2.2573 0.014 6.20 6.01 males 7 1.63 0.01 6.13 300 mg/kg bw 8 1.5929 0.008 5.02 9 2.0888 0.012 5.74 10 2.0201 0.014 6.93 11 2.1328 0.011 5.16 5.31 males 12 1.9677 0.011 5.59 1000 mg/kg bw 13 1.2978 0.007 5.39 14 1.977 0.011 5.56 15 2.4663 0.012 4.87 16 1.3527 0.008 5.91 6.15 females 17 1.2401 0.008 6.45 control 18 1.2873 0.008 6.21 19 1.3878 0.008 5.76 20 1.2479 0.008 6.41 21 1.245 0.008 6.43 6.41 females 22 1.1989 0.008 6.67 300 mg/kg bw 23 1.3348 0.009 6.74 24 1.5306 0.009 5.88 25 1.2649 0.008 6.32 females 26 1.2009 0.007 5.83 6.16 1000 mg/kg bw 27 1.2749 0.009 7.06 28 1.2284 0.007 5.70 29 1.3773 0.008 5.81 30 1.2447 0.008 6.43 Table 2: Copper content in plasma samples
animal no. mg/kg mean 1 1 1.28 males 2 1.3 control 3 1.3 4 1.1 5 1.7 6 2.1 1.48 males 7 1.1 300 mg/kg bw 8 1.5 9 1.2 10 1.5 11 1.5 1.4 males 12 1.1 1000 mg/kg bw 13 1.5 14 1.4 15 1.5 16 1 1.18 females 17 1 control 18 1.3 19 1.1 20 1.5 21 1.5 1.4 females 22 1.1 300 mg/kg bw 23 1 24 1.5 25 1.9 females 26 1.3 1.52 1000 mg/kg bw 27 2.3 28 1 29 1.1 30 1.5 - Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Well documented and acceptable study with the following restrictions: A 91 day subchronic dosed feed toxicity study was conducted in mice, similar to OECD Guideline 408 (Subchronic Oral Toxicity - Rodent: 90-day Study), but not a toxicokinetics study (similar to OECD Guideline 417). However, the study additionally included the examination of systemic copper absorption after exposure to the test material, analyzed in livers and kidneys of the animals.
- Reason / purpose for cross-reference:
- reference to same study
- Objective of study:
- distribution
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 408 (Subchronic Oral Toxicity - Rodent: 90-day Study)
- Principles of method if other than guideline:
- This subchronic toxicity study, similar to OECD Guideline 408, was conducted to assist in selecting Maximum Tolerated Dosages (MTD) for a 104 week chronic study in a dosed feed subchronic study. Additionally the study examined, whether or not systemic absorption of copper occured after exposure to the test material. Copper analyses were conducted in livers and kidneys of the animals.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Pigment Blue 15B
- Analytical purity: The chemical analysis, performed at Midwest Research Institute indicated that the purity was 104.7 % +- 1.1 % (elemental analysis)
- Elemental analysis indicated that the compound contained less than 0.01 % chlorine.
- Structural formula attached as image file (if other than submission substance): see Fig. - Radiolabelling:
- no
- Species:
- mouse
- Strain:
- B6C3F1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Industries
- Age at study initiation: 8.5 weeks
- Weight at study initiation: males: 16 - 23 g; females: 16 - 19 g
- Housing: polycarbonate cages: groups of 5 mice per cage
- Diet: weighed portions of Purina Lab Chow in meal form, mixed together with weighed portions of the test material (see details at "doses/concentrations")
- Water: ad libitum
- Acclimation period: 15 days
ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 23 °C
- Humidity: 40 - 60 %
- Air changes: at least 15 per hour
- Photoperiod: 12 hrs dark / 12 hrs light - Route of administration:
- oral: feed
- Vehicle:
- other: 12 % water was added to the test material as a dust control agent
- Details on exposure:
- Dose levels of 5.0, 2.5, 1.25, 0.6 and 0.3 % (w/w) were selected for both males and females. The selected doses were prepared by mixing weighed portions of purina Lab Chow in meal form with weighed portions of the test material. 12 % water was added to the test material as a dust control agent prior to mixing with the meal. For each dose level, one weekly lot of 4500 g (+ 12 % water compensation) was prepared.
The actual mixtures were composed of the following ingredients:
- Dose level 5.0 % (w/w): 252 g test material and water + 4275 g meal
- Dose level 2.5 % (w/w): 126 g test material and water + 4387.5 g meal
- Dose level 1.25 % (w/w): 63 g test material and water + 4443.75 g meal
- Dose level 0.6 % (w/w): 30.24 g test material and water + 44735 g meal
- Dose level 0.3 % (w/w): 15.12 g test material and water + 4486.5 g meal
Each diet was mixed in a Patterson-Kelly twin shelled V blender for 15 min.
The doses were mixed one or two days prior to the week of their use in the study, and stored at 23 °C.
One analysis was perfomed to determine the accuracy of the mixture concentration. - Duration and frequency of treatment / exposure:
- 90 days
- Dose / conc.:
- 0.3 other: %
- Remarks:
- in diet, approx. 1000 mg/kg bw for males [based on 7.3 g/d average food consumption, 0.023 kg average bw] and approx.1100 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively).
- Dose / conc.:
- 0.6 other: %
- Remarks:
- in diet, approx. 2000 mg/kg bw for males [based on 7.3 g/d average food consumption, 0.023 kg average bw] and approx. 2200 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively).
- Dose / conc.:
- 1.25 other: %
- Remarks:
- in diet, approx. 4000 mg/kg bw for males [based on 7.3 g/d average food consumption, 0.023 kg average bw] and approx. 4700 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively).
- Dose / conc.:
- 2.5 other: %
- Remarks:
- in diet, approx. 8000 mg/kg bw for males [based on 7.3 g/d average food consumption, 0.023 kg average bw] and approx. 9400 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively).
- Dose / conc.:
- 5 other: %
- Remarks:
- in diet, approx. 16000 mg/kg bw for males [based on 7.3 g/d average food consumption, 0.023 kg average bw] and approx. 18700 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively).
- No. of animals per sex per dose / concentration:
- 10 males and 10 females per dose
- Control animals:
- yes, plain diet
- Details on study design:
- - 10 animals were used per sex and dose group.
- Five dose levels of 0.0, 0.3, 0.6, 1.25 and 5.0 % in feed were used in this study (approx. 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. 1100, 2200, 4700, 9300 and 18700 mg/kg bw for females [based on 7.1 g/d average food consumption, 0.019 kg average bw], respectively).
- The selected doses were prepared by mixing together weighed portions of Purina Lab Chow in meal form with weighed portions of the chemical. 12% water was added to the chemical as a dust control agent prior to mixing with the meal.
- Each dosed group received on 91 consecutive days of dosed feed mixture.
- Mice were necropsied on day 92 and 93.
Copper analyses were completed in the liver and kidney tissues and the formalin preserving those tissues from male mice in the highest dose group (5 % w/w) and control groups:
- Tissue samples were prepared for analysis by digesting in 10 ml of concentrated nitric acid until most of the organic material was destroyed. Perchloric acid was then added and the solutions were evaporated to strong fumes, additional nitric acid being added as required. The solutions were then fumed to dryness, the residues were dissolved in 5 % nitric acid and the solutions were diluted to 10 ml.
- Formalin samples were filtered through a Millex-GS 0.22 µm filter unit and 5 ml portions of each sample were prepared for analysis by the procedure used to prepare the tissue samples.
- The samples were then subjected to atomic absorption spectrophotometry to determine copper content:
A Perkin-Elmer Model 5000 atomic absorption spectrophotometer was utilized for the work. A series of 10 ml standard solutions, ranging from 0.05 to 2.0 ppm were prepared in 5 % nitric acid by dilution of a certified standard copper stock solution. These solutions were used to calibrate the instrument, which was programmed to print out data as total microgramms of copper per sample. The prepared sample solutions were used in the same manner as the standards. Concentrations of copper in the tissue samples were calculated by dividing the total microgramms found by the weight of the sample. Concentrations of copper in the formalin samples were calculated on a volume basis. - Statistics:
- Student´s T-test (alpha = 0.05) was used to compare the highest dose group results with control results.
- Preliminary studies:
- No data given.
- Details on absorption:
- No data given.
- Details on distribution in tissues:
- Slight, but statistically significant increases of copper incorporation were reported in the liver tissues (3.98 ppm +- 1.16 ppm; p < 0.05) and kidney (7.47 ppm +- 2.86 ppm; p < 0.05) tissues of treated male animals of the highest dose group, compared to controls (liver: 3.0 ppm +- 0.34 ppm; kidney: 4.66 ppm +- 0.6 ppm). From all the formalin analyses performed, the authors drawed the conclusion that no detectable levels of copper were leached from the preserved tissue into the formalin bath.
However, an evaluation of the results was conducted by expert judgement and the author draw the following conclusions:
The results of the study do not provide unequivocal evidence for a lack of absorption of the test material. However, the total lack of findings during the 13 week study, coupled with the insolubility of the test material and the minimal changes in tissue copper residues strongly suggests that the test material was not appreciably absorbed.
- Details on excretion:
- No data given.
- Metabolites identified:
- not measured
- Details on metabolites:
- No data given.
- Conclusions:
- Interpretation of results: no bioaccumulation potential based on study results
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Well documented and acceptable study with the following restrictions: A 91 day subchronic dosed feed toxicity study was conducted in rats, similar to OECD Guideline 408 (Subchronic Oral Toxicity - Rodent: 90-day Study), but not a toxicokinetics study (similar to OECD Guideline 417). However, the study additionally included the examination of systemic copper absorption after exposure to the test material, analyzed in livers and kidneys of the animals.
- Reason / purpose for cross-reference:
- reference to same study
- Objective of study:
- distribution
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 408 (Subchronic Oral Toxicity - Rodent: 90-day Study)
- Deviations:
- yes
- Principles of method if other than guideline:
- This subchronic toxicity study, similar to OECD Guideline 408, was conducted to assist in selecting Maximum Tolerated Dosages (MTD) for a 104 week chronic study in a dosed feed subchronic study. Additionally the study examined, whether or not systemic absorption of copper occured after exposure to the test material. Copper analyses were conducted in livers and kidneys of the animals.
- GLP compliance:
- no
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): Pigment Blue 15B
- Analytical purity: The chemical analysis, performed at Midwest Research Institute indicated that the purity was 104.7 % +- 1.1 % (elemental analysis)
- Elemental analysis indicated that the compound contained less than 0.01 % chlorine.
- Structural formula attached as image file (if other than submission substance): see Fig. - Radiolabelling:
- no
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Industries
- Weight at study initiation: males: 70 - 105 g; females: 70 - 100 g
- Housing: polycarbonate cages: groups of 5 rats per cage
- Diet: weighed portions of Purina Lab Chow in meal form, mixed together with weighed portions of the test material (see details at "doses/concentrations")
- Water: ad libitum
- Acclimation period: 15 days
ENVIRONMENTAL CONDITIONS
- Temperature: 21 - 23 °C
- Humidity: 40 - 60 %
- Air changes: at least 15 per hour
- Photoperiod: 12 hrs dark / 12 hrs light - Route of administration:
- oral: feed
- Vehicle:
- other: 12 % water was added to the test material as a dust control agent
- Details on exposure:
- Dose levels of 5.0, 2.5, 1.25, 0.6 and 0.3 % (w/w) were selected for both males and females. The selected doses were prepared by mixing weighed portions of purina Lab Chow in meal form with weighed portions of the test material. 12 % water was added to the test material as a dust control agent prior to mixing with the meal. For each dose level, one weekly lot of 4500 g (+ 12 % water compensation) was prepared.
The actual mixtures were composed of the following ingredients:
- Dose level 5.0 % (w/w): 252 g test material and water + 4275 g meal
- Dose level 2.5 % (w/w): 126 g test material and water + 4387.5 g meal
- Dose level 1.25 % (w/w): 63 g test material and water + 4443.75 g meal
- Dose level 0.6 % (w/w): 30.24 g test material and water + 44735 g meal
- Dose level 0.3 % (w/w): 15.12 g test material and water + 4486.5 g meal
Each diet was mixed in a Patterson-Kelly twin shelled V blender for 15 min.
The doses were mixed one or two days prior to the week of their use in the study, and stored at 23 °C.
One analysis was perfomed to determine the accuracy of the mixture concentration. - Duration and frequency of treatment / exposure:
- 90 days
- Dose / conc.:
- 0.3 other: %
- Remarks:
- in diet; approx. 250 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)
- Dose / conc.:
- 0.6 other: %
- Remarks:
- in diet; approx. 500 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)
- Dose / conc.:
- 1.25 other: %
- Remarks:
- in diet; approx. 1100 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)
- Dose / conc.:
- 2.5 other: %
- Remarks:
- in diet; approx. 2200 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)
- Dose / conc.:
- 5 other: %
- Remarks:
- in diet; approx. 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)
- No. of animals per sex per dose / concentration:
- 10 males per dose and 10 females per dose
- Control animals:
- yes, plain diet
- Details on study design:
- The concentrations of the chemical mixture were the same for male and female rats. All dose levels were prepared on a weight per weight basis. There were 5 dose level groups with 10 individuals of each sex in each dosage and control group. Each dosed group received 90 consecutive days of dosed feed mixture. After one day of observation, the animals were necropsied. Animals were observed twice each day for clinical signs, with at least 6 hours between observations. All observations were recorded daily. Additionally, blood sampling was conducted from 10 control rats, 6 males and 4 females.
Copper analyses were completed in the liver and kidney tissues and the formalin preserving those tissues from male rats in the highest dose group (5 % w/w) and control groups:
- Tissue samples were prepared for analysis by digesting in 10 ml of concentrated nitric acid until most of the organic material was destroyed. Perchloric acid was then added and the solutions were evaporated to strong fumes, additional nitric acid being added as required. The solutions were then fumed to dryness, the residues were dissolved in 5 % nitric acid and the solutions were diluted to 10 ml.
- Formalin samples were filtered through a Millex-GS 0.22 µm filter unit and 5 ml portions of each sample were prepared for analysis by the procedure used to prepare the tissue samples.
- The samples were then subjected to atomic absorption spectrophotometry to determine copper content:
A Perkin-Elmer Model 5000 atomic absorption spectrophotometer was utilized for the work. A series of 10 ml standard solutions, ranging from 0.05 to 2.0 ppm were prepared in 5 % nitric acid by dilution of a certified standard copper stock solution. These solutions were used to calibrate the instrument, which was programmed to print out data as total microgramms of copper per sample. The prepared sample solutions were used in the same manner as the standards. Concentrations of copper in the tissue samples were calculated by dividing the total microgramms found by the weight of the sample. Concentrations of copper in the formalin samples were calculated on a volume basis. - Details on dosing and sampling:
- PHARMACOKINETIC STUDY (distribution)
- Tissues and body fluids sampled: liver and kidneys - Statistics:
- Student´s T-test (alpha = 0.05) was used to compare the highest dose group results with control results.
- Details on absorption:
- No data given.
- Details on distribution in tissues:
- No statistically significant increase of residual copper incorporation was neither reported for the liver tissues (2.82 ppm +- 0.34 ppm) nor for the kidney tissues (5.62 ppm +- 0.49 ppm) of the treated male rats of the highest dose group, compared to residual copper incorporation found in controls (liver 2.78 ppm +- 0.51 ppm; kidney 5.30 ppm +- 0.83 ppm). From all the formalin analyses performed, the authors drawed the conclusion that no detectable levels of copper were leached from the preserved tissue into the formalin bath.
- Details on excretion:
- No data given.
- Metabolites identified:
- not measured
- Details on metabolites:
- No data given.
- Conclusions:
- Interpretation of results: no bioaccumulation potential based on study results
Referenceopen allclose all
Table 1: Copper determinations in tissues and formalin of male mice from the subchronic study, treated with the test material for 91 days
male animal # |
ppm copper |
|
||
|
liver |
kidney |
formalin |
remark |
highest dose group (5 % w/w) |
|
|
|
|
1 |
7.0 |
14.5 |
-- |
|
2 |
3.2-3.6 * |
6.8 |
-- |
* results of 2 analyses |
3 |
3.4 |
7.7 |
-- |
|
4 |
3.4 |
4.8 |
-- |
|
5 |
3.5 |
6.3 |
-- |
|
6 |
3.7 |
7.3 |
-- |
|
7 |
3.9 |
6.4 |
-- |
|
8 |
4.1 |
8.2 |
-- |
|
9 |
3.3-3.6 * |
5.2 |
-- |
* results of 2 analyses |
control |
|
|
|
|
1 |
3.5 |
4.2 |
0.1 |
|
2 |
3.1 |
3.8 |
0.1 |
|
3 |
3.1 |
4.6 |
0.1 |
|
4 |
2.8 |
4.6 |
0.1 |
|
5 |
2.9 |
4.2 |
0.1 |
|
6 |
3.2 |
4.7 |
0.1 |
|
7 |
3.2 |
5.8 |
0.1 |
|
8 |
2.9 |
5.3 |
0.1 |
|
9 |
2.3 |
4.7 |
0.1 |
|
Table 1: Copper determinations in tissues and formalin of male rats from the subchronic study, treated with the test material for 90 days
male animal # |
ppm copper |
|
||
|
liver |
kidney |
formalin |
remark |
highest dose group (5 % w/w) |
|
|
|
|
1 |
4.6 - 4.3* |
8.4 |
0.1 |
* results of 2 analyses |
2 |
5.9 |
12.3 |
0.1 |
|
3 |
4.1 - 4.4* |
8.6 - 10.1* |
0.1 |
* results of 2 analyses |
4 |
6.4 |
7.7 |
0.1 |
|
5 |
3.2 |
6.7 |
0.1 |
|
6 |
3.5 |
5.8 |
0.1 |
|
7 |
3.7 |
8.1 |
0.1 |
|
8 |
3.5 - 4.1 |
8.1 |
0.1 |
|
9 |
3.1 |
8.7 - 8.6* |
0.1 |
* results of 2 analyses |
10 |
4.6 - 4.5 |
7.2 |
0.1 |
|
control |
|
|
|
|
1 |
3.1 |
3.7 - 4.0* |
0.1 |
* results of 2 analyses |
2 |
3.3 |
4.1 |
0.1 |
|
3 |
3.2 |
4.9 - 4.6* |
0.1 |
* results of 2 analyses |
4 |
3.7 - 4.0* |
5.1 |
0.1 |
* results of 2 analyses |
5 |
3.0 |
4.1 |
0.1 |
|
6 |
2.8 |
5.4 |
0.1 |
|
7 |
2.9 |
2.9 - 3.4* |
0.1 |
* results of 2 analyses |
8 |
2.6 |
5.5 |
0.1 |
|
9 |
2.6 |
5.4 |
0.1 |
|
10 |
3.3 - 3.6* |
5.4 |
0.1 |
* results of 2 analyses |
Description of key information
The substance is an inert high molecular weight organic copper complex. It fulfills the criteria of the definition of a nanomaterial in the European Union.
Is not systemically available after ingestion as indicated by lack of increased plasma and liver copper concentrations and absence of toxicity after 14 day gavage dosing of rats with 300 or 1000 mg/kg bw.
Key value for chemical safety assessment
- Bioaccumulation potential:
- no bioaccumulation potential
Additional information
The substance consists of a mixture of copper phthalocyanine with 0 to 3 1 H-isoindole-dione covalently bound substituents. The average degree of substitution is 2.48 which results in an average mass of 970 g/mol. The substance insoluble in water as examined via total organic carbon and copper content (3 μg/L at loading rate of 0.1 g/L
) and poorly soluble in octanol (1 mg/L at a loading rate of 0.1 g/L). All these properties indicate that transport through biological membranes is hindered. Absence of toxicity upon ingestion in subacute toxicity studies in rats has been observed for related copper phthalocyanine pigments and the copper phthalocyanine core (CAS nos 147-14-8, 75247-18 -6, 81457-65 -0) and inert organic pigments in general.
In support of this, 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 and included clincal chemistry and haematology parameters. A similar 14 -day study with an acid-labile and lower molecular weight organic copper pigment (Pigment Yellow 129) had shown that such exposure resulted in a significant increase in liver copper concentrations. In contrast, the target substance did not cause increased copper concentrations in liver and plasma after 14 days of oral dosing at the limit dose. In addition, no blue discoloration of internal tissues were observed and there was no greenish urine discoloration. Clinical chemistry and haematology parameters were not affected and overall no adverse effects were noted. From this it is concluded that the target substance is not taken up by the body after ingestion.
For the weight-of-evidence approach, the same type of information obtained with the copper phthalocyanine core (CAS 147 -14 -8) after subchronic feed application of high doses is also provided. It shows that no copper accumulation in liver results from subchronic high dose exposure.
A read-across justification document with structures and data matrices is attached. Target and structural analogues fulfill the definition of a nanomaterial in the European Union.
Considering the insolubility and the high molecular weight, it is expected that the substance is not able to penetrate the skin.
Inhalation is expected to result in local effects related to inert particles.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.