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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Description of key information
A 14-day study in rats with 300 and 1000 mg/kg bw of the substance showed absence of toxicity. No indication of systemic uptake as determined via serum copper concentrations was observed. For support, data on the smaller copper phthalocyanine core (CAS 147-15-8) is used. It shows lack of effects in rats and mice upon subchronic feed exposure.
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 2014-2015
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: study design to support read-across; no guideline-compliant study. Adequate in design and documentation
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- 14-day gavage study with clinical chemistry, haematology, some organ weights and examination of plasma and liver concentrations of copper
- GLP compliance:
- no
- Limit test:
- 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 - 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: drinking water containing 0.5% carboxymethylcellulose with about 5 mg/100 ml Cremophor EL
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Daily
The substance is a homogenous suspension. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 14 days
- Frequency of treatment:
- daily
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Data on structurally related copper phthalocyanines
- Rationale for animal assignment (if not random): on the basis of the animal weight. - Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily
BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 3, 7 and 14.
Food consumption and water consumption were determined on study days 3, 7 and 14.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: day 14
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes
- How many animals: all
- Parameters listed below were examined:
1. Leukocytes
2. Erythrocytes
3. Hemoglobin
4. Hematocrit
5. Mean corpuscular volume (MCV)
6. Mean corpuscular hemoglobin (MCH)
7. Mean corpuscular hemoglobin concentration (MCHC)
8. Platelets
9. Differential blood count
10. Reticulocytes
11 . Preparation of blood smears (on ly evaluated blood smears will be archived)
12. Prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: day 14
- Animals fasted: Yes
- How many animals: all
- Parameters listed below were examined.
1. Alanine aminotransferase
2. Aspartate aminotransferase
3. Alkaline phosphatase
4. Serum -glutamyl transferase
5. Sodium
6. Potassium
7. Chloride
8. lnorg. phosphate
9. Calcium
10. Urea
11 . Creatinine
12. Glucose
13. Total bilirubin
14. Totalprotein
15. Albumin
16. Globulins
17. Triglycerides
18. Cholesterol
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
OTHER: 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.
Half of the liver tissue (divided in two parts) of all animals were deep frozen for each animal and stored at -80°C for the determination of the test substance by the analytical chemistry. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Organ Weights:
Adrenal glands, Kidneys, Liver, Spleen
HISTOPATHOLOGY: Yes (all gross lesion, Adrenal glands, Kidneys, Liver, Spleen) - Statistics:
- Food consumption, water consumption, body weight, body weight change: , Dunnett test (two-sided)
Clinical pathology parameters, organ weights and body weights of anesthetized animals: KRUSKAL-WALLIS and WILCOXON - Clinical signs:
- no effects observed
- Description (incidence and severity):
- No test substance-related, adverse findings were observed. During the administration period, discolored feces were observed in all animals of test group 1 and 2 (300 and 1000 mg/kg bw/d). These findings were clearly related to the color of the test substance and assessed as being non-adverse.
- Mortality:
- no mortality observed
- Description (incidence):
- No animal died prematurely in the present study.
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- The discoloration of intestinal content (stomach, jejunum, colon) in treated animals was related to the color of test substance. No discoloration of organs was observed.
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- not examined
- Dose descriptor:
- NOEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No indication of systemic uptake from plasma and liver copper levels. No adverse effects on haematology, clinical chemistry, body weights, organ weights.
- Critical effects observed:
- no
- Conclusions:
- There is no indication of systemic uptake after ingestion based on the absence of findings and the absence of elevated copper concentrations in plasma after 14 days of exposure.
Reference
Red blood cell and coagulation parameters (males)
control | 300 mg/kg bw | 1000 mg/kd bw | ||
RBC | Mean | 7.68 k | 7.60 | 7.73 |
[tera/L] | S.d. | 0.18 | 0.20 | 0.47 |
N | 5 | 5 | 5 | |
Median | 7.69 | 7.50 | 7.75 | |
HGB | Mean | 8.6 k | 8.5 | 8.7 |
[mmol/L] | S.d. | 0.2 | 0.3 | 0.4 |
N | 5 | 5 | 5 | |
Median | 8.6 | 8.7 | 8.8 | |
HCT | Mean | 0.420 k | 0.416 | 0.424 |
[L/L] | S.d. | 0.008 | 0.009 | 0.016 |
N | 5 | 5 | 5 | |
Median | 0.418 | 0.418 | 0.423 | |
MCV | Mean | 54.7 k | 54.7 | 55.0 |
[fL] | S.d. | 1.1 | 1.5 | 2.1 |
N | 5 | 5 | 5 | |
Median | 54.6 | 53.7 | 54.7 | |
MCH | Mean | 1.12 k | 1.12 | 1.13 |
[fmol] | S.d. | 0.02 | 0.04 | 0.03 |
N | 5 | 5 | 5 | |
Median | 1.13 | 1.11 | 1.13 | |
MCHC | Mean | 20.47 k | 20.52 | 20.55 |
[mmol/L] | S.d. | 0.11 | 0.32 | 0.34 |
N | 5 | 5 | 5 | |
Median | 20.46 | 20.56 | 20.68 | |
RET | Mean | 2.8 k | 2.6 | 2.5 |
[%] | S.d. | 0.5 | 0.5 | 0.6 |
N | 5 | 5 | 5 | |
Median | 2.8 | 2.7 | 2.5 | |
PLT | Mean | 818 k | 877 | 708 |
[giga/L] | S.d. | 110 | 89 | 99 |
N | 5 | 5 | 5 | |
Median | 774 | 911 | 703 | |
HQT | Mean | 36.7 k | 38.8 | 38.5 |
[sec] | S.d. | 0.9 | 1.9 | 1.4 |
N | 5 | 5 | 5 | |
Median | 36.6 | 37.4 | 38.3 |
Red blood cell and coagulation parameters (females)
control | 300 mg/kg bw | 1000 mg/kd bw | ||
RBC | Mean | 7.83 k | 7.61 | 7.73 |
[tera/L] | S.d. | 0.30 | 0.19 | 0.13 |
N | 5 | 5 | 5 | |
Median | 7.67 | 7.59 | 7.81 | |
HGB | Mean | 8.5 k | 8.4 | 8.6 |
[mmol/L] | S.d. | 0.2 | 0.2 | 0.2 |
N | 5 | 5 | 5 | |
Median | 8.5 | 8.4 | 8.6 | |
HCT | Mean | 0.405 k | 0.398 | 0.406 |
[L/L] | S.d. | 0.011 | 0.009 | 0.012 |
N | 5 | 5 | 5 | |
Median | 0.398 | 0.401 | 0.412 | |
MCV | Mean | 51.8 k | 52.2 | 52.5 |
[fL] | S.d. | 2.1 | 0.9 | 1.1 |
N | 5 | 5 | 5 | |
Median | 52.2 | 52.1 | 52.9 | |
MCH | Mean | 1.09 k | 1.10 | 1.11 |
[fmol] | S.d. | 0.04 | 0.02 | 0.02 |
N | 5 | 5 | 5 | |
Median | 1.10 | 1.09 | 1.12 | |
MCHC | Mean | 21.09 k | 21.08 | 21.16 |
[mmol/L] | S.d. | 0.24 | 0.11 | 0.27 |
N | 5 | 5 | 5 | |
Median | 20.99 | 21.08 | 21.23 | |
RET | Mean | 1.7 k | 1.8 | 1.6 |
[%] | S.d. | 0.2 | 0.4 | 0.5 |
N | 5 | 5 | 5 | |
Median | 1.8 | 1.6 | 1.7 | |
PLT | Mean | 828 k | 839 | 756 |
[giga/L] | S.d. | 70 | 101 | 83 |
N | 5 | 5 | 5 | |
Median | 846 | 801 | 770 | |
HQT | Mean | 35.1 k | 35.1 | 35.9 |
[sec] | S.d. | 2.1 | 1.5 | 1.4 |
N | 5 | 5 | 5 | |
Median | 36.4 | 35.2 | 35.3 |
Total white and differential blood cell count (males)
control | 300 mg/kg bw | 1000 mg/kd bw | ||
WBC | Mean | 5.57 k | 5.62 | 5.36 |
[giga/L] | S.d. | 0.96 | 1.75 | 1.98 |
N | 5 | 5 | 5 | |
Median | 5.63 | 5.21 | 5.26 | |
NEUTA | Mean | 0.61 k | 0.70 | 0.93 |
[giga/L] | S.d. | 0.16 | 0.32 | 0.23 |
N | 5 | 5 | 5 | |
Median | 0.64 | 0.65 | 0.93 | |
LYMPHA | Mean | 4.73 k | 4.72 | 4.16 |
[giga/L] | S.d. | 0.84 | 1.53 | 1.72 |
N | 5 | 5 | 5 | |
Median | 4.72 | 4.30 | 4.29 | |
MONOA | Mean | 0.12 k | 0.10 | 0.10 |
[giga/L] | S.d. | 0.03 | 0.03 | 0.06 |
N | 5 | 5 | 5 | |
Median | 0.11 | 0.09 | 0.08 | |
EOSA | Mean | 0.06 k | 0.06 | 0.14 |
[giga/L] | S.d. | 0.02 | 0.03 | 0.09 |
N | 5 | 5 | 5 | |
Median | 0.06 | 0.05 | 0.09 | |
BASOA | Mean | 0.01 k | 0.01 | 0.01 |
[giga/L] | S.d. | 0.01 | 0.00 | 0.01 |
N | 5 | 5 | 5 | |
Median | 0.01 | 0.01 | 0.01 | |
LUCA | Mean | 0.03 k | 0.03 | 0.03 |
[giga/L] | S.d. | 0.02 | 0.01 | 0.01 |
N | 5 | 5 | 5 | |
Median | 0.03 | 0.03 | 0.02 | |
NEUT | Mean | 11.0 v | 12.6 | 18.3 ** |
[%] | S.d. | 2.2 | 3.9 | 4.4 |
N | 5 | 5 | 5 | |
Median | 10.9 | 13.6 | 15.6 | |
LYMPH | Mean | 84.9 v | 83.8 | 76.4 * |
[%] | S.d. | 2.3 | 4.3 | 5.8 |
N | 5 | 5 | 5 | |
Median | 86.2 | 82.6 | 79.3 | |
MONO | Mean | 2.1 k | 1.7 | 1.8 |
[%] | S.d. | 0.6 | 0.3 | 0.8 |
N | 5 | 5 | 5 | |
Median | 2.1 | 1.7 | 1.6 | |
EOS | Mean | 1.2 k | 1.1 | 2.7 |
[% ] | S.d. | 0.4 | 0.3 | 1.9 |
N | 5 | 5 | 5 | |
Median | 1.0 | 1.1 | 1.7 | |
BASO | Mean | 0.3 k | 0.2 | 0.3 |
[%] | S.d. | 0.1 | 0.1 | 0.1 |
N | 5 | 5 | 5 | |
Median | 0.2 | 0.2 | 0.2 | |
LUC | Mean | 0.6 k | 0.6 | 0.5 |
[%] | S.d. | 0.2 | 0.1 | 0.2 |
N | 5 | 5 | 5 | |
Median | 0.6 | 0.6 | 0.6 |
Total white and differential blood cell count (females)
control | 300 mg/kg bw | 1000 mg/kd bw | ||
WBC | Mean | 4.53 k | 4.29 | 4.49 |
[giga/L] | S.d. | 0.72 | 0.91 | 1.74 |
N | 5 | 5 | 5 | |
Median | 4.51 | 4.45 | 3.59 | |
NEUTA | Mean | 0.38 k | 0.47 | 0.55 |
[giga/L] | S.d. | 0.03 | 0.15 | 0.15 |
N | 5 | 5 | 5 | |
Median | 0.39 | 0.38 | 0.50 | |
LYMPHA | Mean | 3.98 k | 3.67 | 3.78 |
[giga/L] | S.d. | 0.68 | 1.00 | 1.53 |
N | 5 | 5 | 5 | |
Median | 3.96 | 3.94 | 3.04 | |
MONOA | Mean | 0.08 k | 0.06 | 0.07 |
[giga/L] | S.d. | 0.03 | 0.02 | 0.05 |
N | 5 | 5 | 5 | |
Median | 0.08 | 0.05 | 0.06 | |
EOSA | Mean | 0.07 k | 0.05 | 0.06 |
[giga/L] | S.d. | 0.02 | 0.01 | 0.05 |
N | 5 | 5 | 5 | |
Median | 0.07 | 0.05 | 0.05 | |
BASOA | Mean | 0.01 k | 0.01 | 0.01 |
[giga/L] | S.d. | 0.00 | 0.01 | 0.01 |
N | 5 | 5 | 5 | |
Median | 0.01 | 0.01 | 0.01 | |
LUCA | Mean | 0.02 k | 0.03 | 0.02 |
[giga/L] | S.d. | 0.00 | 0.01 | 0.01 |
N | 5 | 5 | 5 | |
Median | 0.02 | 0.03 | 0.01 | |
NEUT | Mean | 8.5 k | 11.7 | 13.1 |
[%] | S.d. | 1.4 | 5.6 | 3.3 |
N | 5 | 5 | 5 | |
Median | 8.2 | 8.5 | 11.8 | |
LYMPH | Mean | 87.7 k | 84.7 | 83.6 |
[%] | S.d. | 1.1 | 5.8 | 3.2 |
N | 5 | 5 | 5 | |
Median | 87.8 | 87.5 | 84.0 | |
MONO | Mean | 1.6 k | 1.5 | 1.5 |
[%] | S.d. | 0.5 | 0.3 | 0.5 |
N | 5 | 5 | 5 | |
Median | 1.6 | 1.4 | 1.6 | |
EOS | Mean | 1.4 k | 1.1 | 1.2 |
[%] | S.d. | 0.1 | 0.1 | 0.4 |
N | 5 | 5 | 5 | |
Median | 1.4 | 1.2 | 1.1 | |
BASO | Mean | 0.3 k | 0.3 | 0.2 |
[%] | S.d. | 0.1 | 0.1 | 0.1 |
N | 5 | 5 | 5 | |
Median | 0.2 | 0.3 | 0.3 | |
LUC | Mean | 0.5 v | 0.6 | 0.4 |
[%] | S.d. | 0.2 | 0.1 | 0.1 |
N | 5 | 5 | 5 | |
Median | 0.5 | 0.6 | 0.4 |
Enzymes (males)
control | 300 mg/kg bw | 1000 mg/kd bw | ||
ALT | Mean | 0.85 k | 0.87 | 0.87 |
[µkat/L] | S.d. | 0.20 | 0.07 | 0.14 |
N | 5 | 5 | 5 | |
Median | 0.84 | 0.82 | 0.86 | |
AST | Mean | 1.66 k | 1.67 | 1.70 |
[µkat/L] | S.d. | 0.16 | 0.36 | 0.29 |
N | 5 | 5 | 5 | |
Median | 1.68 | 1.56 | 1.71 | |
ALP | Mean | 2.50 k | 2.92 | 2.65 |
[µkat/L] | S.d. | 0.11 | 0.55 | 0.55 |
N | 5 | 5 | 5 | |
Median | 2.52 | 2.76 | 2.38 | |
GGT_C | Mean | 0 | 0 | 0 |
[nkat/L] | S.d. | 0 | 0 | 0 |
N | 5 | 5 | 5 | |
Median | 0 | 0 | 0 |
Enzymes (females)
control | 300 mg/kg bw | 1000 mg/kd bw | ||
ALT | Mean | 0.60 k | 0.71 | 0.67 |
[µkat/L] | S.d. | 0.10 | 0.13 | 0.18 |
N | 5 | 5 | 5 | |
Median | 0.56 | 0.64 | 0.67 | |
AST | Mean | 1.52 k | 1.62 | 1.69 |
[µkat/L] | S.d. | 0.06 | 0.18 | 0.23 |
N | 5 | 5 | 5 | |
Median | 1.51 | 1.56 | 1.58 | |
ALP | Mean | 1.54 k | 2.18 | 2.09 |
[µkat/L] | S.d. | 0.43 | 0.89 | 0.66 |
N | 5 | 5 | 5 | |
Median | 1.73 | 1.75 | 2.28 | |
GGT_C | Mean | 0 | 0 | 0 |
[nkat/L] | S.d. | 0 | 0 | 0 |
N | 5 | 5 | 5 | |
Median | 0 | 0 | 0 |
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- 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 14-day study in rats with 300 and 1000 mg/kg bw of the substance showed absence of toxicity as determined by clincical chemistry, haematology, organ weight determinations, clinical observations and body weight measurements. Intestinal passage was indicated by a blue discoloration of feces; there was no discoloration of internal organs or of urine. For the full subacute toxicity study, read-across is done to the core structure.
Read-across to the blue pigment copper phthalocyanine (CAS 147-14-8) is justified because the target substance phthalimidomethyl copper phthalocyanine is as inert as its core structure. All available toxicological data (acute toxicity, irritation, sensitization, 14-day oral study, genotoxicity) show absence of adverse effects. The measured solubility in water is as low as for copper phthalocyanine. The solubility in octanol is higher, but with 1 mg/L still very low. The phthalimido group is unreactive and does not introduce a new hazard. For details on phthalimide it is referred to the dissiminated ECHA dossier.Phthalimide is not classified based on experimental data submitted to ECHA for a 10-100 tpa registration including an OECD 422 study (accessed September 9, 2015).
The same pattern of an inert core and a non-reactive derivative is observed for the violet pigment quinacridone and its phthalimido quinacridone derivative (CAS 332142-67-3). The latter is of interest because the molecular weight of both the core and the derivative are lower than that of the target substance. This would make any hypothetical systemic uptake more likely. The phthalimido quinacridone derivative (CAS 332142-67-3) is nontoxic in all studies (subacute oral toxicity at the limit dose, genotoxicity, acute toxicity, irritation and sensitization; see data matrix). If of interest, data on the quinacridone core (Pigment Violet 19, CAS 1047-16-1) it is referred to the dissiminated REACH dossier. No adverse effects are were reported in any study.
Organic pigments are poorly soluble in water and organic solvents. For analytical purposes of the target substance, concentrated sulphuric acid needs to be used as other solvents are not suitable. In the absence of solubility, transport processes are not possible and no systemic uptake takes place.
For both copper phthalocyanine and its phthalimido derivative, copper concentrations in tissues were determined after 90-day and 14-day oral dosing of doses of 1000 mg/kg bw or higher. For neither substance, there was an increase in systemic copper concentrations. This is a strong indicator that there is no systemic uptake. In case of another organic copper pigment (Pigment Yellow 129) which disintegrates in stomach acid, 14-day oral dosing of 300 and 1000 mg/kg bw caused a clear and dose-dependent increase in liver copper concentrations. Liver is the known organ for copper storage. The fact that even 3-months feed application of up to 4500 mg/kg bw of rats and mice did not result in increased systemic copper concentrations shows that this core structure is inert. Indeed, this result was used as argument by the US authorities not to perform a carcinogenicity study under the US National Toxicology Program.
In conclusion, it is predicted that the NOEL for a 28-day oral toxicity study (OECD 407) will be at the limit dose.
A full read-across justification document with data matrix is attached in the toxicokinetic section of IUCLID.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint: Study on test substance
Justification for classification or non-classification
Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result, the substance is not considered to be classified for repeated dose toxicity under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.
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.