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EC number: 209-886-5 | CAS number: 596-49-6
- 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
Repeated dose toxicity: oral
Administrative data
- Endpoint:
- repeated dose toxicity: oral
- Remarks:
- combined repeated dose and carcinogenicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed publication
Data source
Reference
- Reference Type:
- publication
- Title:
- Lifetime toxicity/carcinogenicity studies of FD & C BLUE No. 1 (BRILLIANT BLUE FCF) in rats and mice
- Author:
- J. F. Borzelleca, K. Depukat and J. B. Hallagan
- Year:
- 1 990
- Bibliographic source:
- Food Chem. Toxicol. Vol. 28, No. 4, pp. 221-234, 1990 ;
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- Combined Repeated dose carcinogenicity study was performed to evaluate the toxic nature of Brilliant Blue FCF.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)]amino]-2'-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt
- EC Number:
- 223-339-8
- EC Name:
- Dihydrogen (ethyl)[4-[4-[ethyl(3-sulphonatobenzyl)]amino]-2'-sulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene](3-sulphonatobenzyl)ammonium, disodium salt
- Cas Number:
- 3844-45-9
- IUPAC Name:
- disodium 2-({4-[ethyl(3-sulfonatobenzyl)amino]phenyl}{4-[ethyl(3-sulfonatobenzyl)iminio]cyclohexa-2,5-dien-1-ylidene}methyl)benzenesulfonate
- Details on test material:
- - Name of test material: FD & C BLUE No. 1 (Brilliant blue FCF)
- Molecular formula: C37H36N2O9S3.2Na
- Molecular weight: 792.8586 g/mol
- Smiles notation: C(=C1\C=C\C(=[N+](\Cc2cc(ccc2)S(=O)(=O)[O-])CC)C=C1)(/c1c(cccc1)S(=O)(=O)[O-])c1ccc(cc1)N(Cc1cc(ccc1)S(=O)(=O)[O-])CC.[Na+].[Na+]
- Substance type: Organic
- Physical state: No data
- Analytical purity: 90%
- Impurities: 10% consisted of subsidiary colourings, volatile chlorides and sulphates, and uncombined intermediates.
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- other: Charles River CD-l, COBS (ICR-derived)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: Mice were housed individually in hanging wiremesh cages.
- Diet (e.g. ad libitum): basal diet of certified Purina Laboratory Rodent Chow No. 5001 (Ralston Purina Company, Inc., St Louis, MO) ad libitum
- Water (e.g. ad libitum): Water ad libitum
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21°C
- Humidity (%): 40-60%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12-hr light/dark cycle
IN-LIFE DATES: From: To: No data
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- other: Basal diet(Purina Laboratory Rodent Chow No. 5001 (Ralston Purina Company, Inc., St Louis, MO))
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Diets were blended in a twin-shell blender and were prepared and presented weekly. Assays were performed to assess the homogeneity and stability of FD & C Blue No. l in the prepared diets before study initiation.
DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): basal diet of certified Purina Laboratory Rodent Chow No. 5001 (Ralsto Purina Company, Inc., St Louis, MO)
- Storage temperature of food: 20-21°C
VEHICLE
- Justification for use and choice of vehicle (if other than water): No data
- Concentration in vehicle: No data
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses of compound concentration were conducted weekly during the first 13 wk of study, and then monthly thereafter. Analyses of the basal feed
for heavy metals, chlorinated hydrocarbons, and aflatoxin were conducted on all lots of feed used during the study. These analyses demonstrated that the basal feed contained acceptably low levels of contaminants, that the diets were prepared properly, and that the dietary content of the test material was stable. - Duration of treatment / exposure:
- 24 months (104 weeks)
- Frequency of treatment:
- daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0%, 0%, 0.5%, 1.5% or 5.0% (0, 0, 714.28, 2142.85 or 7142.85 mg/Kg bw/day)
Basis:
nominal in diet
- No. of animals per sex per dose:
- Total: 600
0 mg/Kg bw/day: 60 males and 60 females
0 mg/Kg bw/day: 60 males and 60 females
714.28 mg/Kg bw/day: 60 males and 60 females
2142.85 mg/Kg bw/day: 60 males and 60 females
7142.85 mg/Kg bw/day: 60 males and 60 females - Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: No data
- Rationale for animal assignment (if not random): No data
- Rationale for selecting satellite groups: No data
- Post-exposure recovery period in satellite groups: No data
- Section schedule rationale (if not random): No data - Positive control:
- No data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least twice daily (with a minimum of 5 hr between observations)
- Cage side observations checked in table [No.?] were included. morbidity and mortality
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: at least twice daily (with a minimum of 5 hr between observations); Detailed physical examinations for signs of toxicity and palpation for masses were conducted weekly.
BODY WEIGHT: Yes
- Time schedule for examinations: weekly through the first 14 wk, biweekly for wk 16-26 and monthly thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes, weekly through the first 14 wk, biweekly for wk 16-26 and monthly thereafter
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data
OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: after 3, 6, 12, 18 and 24 months of the study
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 10/sex of each dose level
- Parameters checked in table [No.?] were examined. haemoglobin, haematocrit, total erythrocyte count, total and differential leucocyte counts, and erythrocyte morphology.
CLINICAL CHEMISTRY: No data
- Time schedule for collection of blood: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined. No data
URINALYSIS: No data
- Time schedule for collection of urine: No data
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. No data
NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data
OTHER: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Autopsies were conducted on all animals that died spontaneously, were killed in a moribund condition, or were killed on schedule. Organ weights were recorded for the brain, gonads, kidneys, liver, spleen and thyroid, and relative organ weights were calculated.
HISTOPATHOLOGY: Yes, Histology was conducted on all animals from the two control groups and from the 7142.85 mg/Kg bw/day group. The
following tissues were examined histologically: Gall bladder, adrenal (two), aorta (abdominal), bone and marrow (femur), blood smear, brain (three sections: frontal cortex and basal ganglia, parietal cortex and thalamus, and cerebellum and pons), oesophagus, eye (two, with optic nerve), heart (with coronary vessels), intestine (caecum, colon, duodenum and ileum), kidneys (two), liver, lung and mainstem bronchi (lungs inflated with formalin), lymph nodes (mesenteric and mediastinal), mammary gland (inguinal), nerve (sciatic), ovaries, pancreas, pituitary, prostate, salivary gland (mandibular), seminal vesicles (two), skeletal muscle (biceps femoris), skin, spinal cord (cervical), spleen, stomach, testes with epididymides, thymus, thyroid with parathyroid, trachea, urinary bladder (inflated with formalin), uterus, any tissue with gross changes of an uncertain nature together with an apparently normal section of the same tissue, and any tissue masses or suspect tumours together with regional lymph nodes. - Other examinations:
- No data
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- CLINICAL SIGNS AND MORTALITY:
Clinical signs: A blue staining of the hair, exposed skin and faeces was observed at all treatment levels. Other physical observations were seen in similar incidence among control and treated groups and were considered common for this strain.
Mortality: Mortality and survival of rats was not affected by treatment
BODY WEIGHT AND WEIGHT GAIN: Group mean body weights for treated mice were slightly lower when compared with either control group at various intervals. Statistically significant decreases in body weight (P < 0.01) occurred at some intervals for males and females in the 2142.85 and 7142.85 mg/Kg bw/day groups. Statistical significance was mainly seen when values were compared with control group IB or with the combined control means.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Mean food consumption throughout the study remained similar for control and treated mice
FOOD EFFICIENCY: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
OPHTHALMOSCOPIC EXAMINATION: No data
HAEMATOLOGY: Haematological values were similar among control and treated mice throughout the study. Occasional statistically significant decreases in mean haemoglobin, haematocrit and leucocyte values of treated mice were noted, but were not considered toxicologically significant.
CLINICAL CHEMISTRY: No data
URINALYSIS: No data
NEUROBEHAVIOUR: No data
ORGAN WEIGHTS: No data
GROSS PATHOLOGY: No data
HISTOPATHOLOGY: NON-NEOPLASTIC A variety of microscopic lesions was observed at similar incidence in control and treated mice. The 7142.85 mg/Kg bw/day females exhibited an increased incidence of haemangioma of the spleen, but the increase was statistically significant (P < 0.01) only for the unadjusted trend analysis.
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
HISTORICAL CONTROL DATA (if applicable)
OTHER FINDINGS: No data
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 7 354 other: mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No mortality; no effect on hematology, behavior, and morbidity; no carcinogenicity. at 5 % concentration (7354 mg/kg bw/day)
- Dose descriptor:
- NOAEL
- Effect level:
- 8 966 other: mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No mortality; no effect on hematology, behavior, and morbidity; no carcinogenicity. at 5 % concentration (8966 mg/kg bw/day)
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table: Survival and group mean body weights
Dietary concentration (mg/Kg bw/day) |
No surviving at the end of the study (Total: 60) |
Final body weight (Mean±SD) |
||
|
Males |
Females |
Males |
Females |
0 |
25 |
24 |
38±5 |
32 ± 5 |
0 |
23 |
31 |
38±3 |
33±4 |
714.28 |
25 |
31 |
36±5 |
31 ± 3 |
2142.85 |
28 |
28 |
35 ± 3 |
31 ± 4 |
7142.85 |
33 |
31 |
36 ± 4 |
29 ± 4 |
Table: Mean food and compound consumption
Dietary concentration (mg/Kg bw/day) |
Food consumption (g/Kg/day) |
Compound consumption (g/Kg/day) |
||
|
Males |
Females |
Males |
Females |
0 |
133±16 |
169±22 |
- |
- |
0 |
132±15 |
163±22 |
- |
- |
714.28 |
132±16 |
164±21 |
661±79 |
819±105 |
2142.85 |
138±17 |
171±24 |
2064±251 |
2562±357 |
7142.85 |
147±17 |
179±22 |
7354±836 |
8966±1115 |
Applicant's summary and conclusion
- Conclusions:
- In repeated dose chronic toxicity study dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively) FD & C Blue No. 1 to mouse for 104 weeks did not demonstrate consistent biologically significant, compound-related adverse effects on behavior, morbidity, mortality, haematology, general physical observations. Thus, the No Observed Adverse Effect Level (NOAEL) for chronic repeated dose toxicity by oral route was considered to be 7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively.
- Executive summary:
Combined Repeated dose carcinogenicity study was performed to evaluate the toxic nature of Brilliant Blue FCF. FD & C Blue No. 1 was fed to CD-1 mice as a dietary admixture in lifetime toxicity/carcinogenicity studies at dose levels of 0.0%, 0.0%, 0.5%, 1.5% or 5.0% (0, 0, 714.28, 2142.85 or 7142.85 mg/Kg bw/day) in a lifetime toxicity/ carcinogenicity study. The maximum exposure time was 104 wk for both males and females. Dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively) FD & C Blue No. 1 to mouse for 104 weeks did not demonstrate consistent biologically significant, compound-related adverse effects on behavior, morbidity, mortality, haematology, general physical observations. Thus, the no-observed-adverse-effect level (NOAEL) established in this study is a dietary concentration of 5.0% (7354 mg/kg/day and 8966 mg/kg/day for male and female mice, respectively).
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