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EC number: 220-168-0 | CAS number: 2650-18-2
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- other: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- The study is conducted on a read across test material. The complete read across justification is attached in section 13. The reliability of the original study is 2.
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:
- Borzelleca, J.F., Depukat, K., Hallagan, J.B.
- Year:
- 1 990
- Bibliographic source:
- Fd. Chem. Toxicol. 28, 221-234 (1990)
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 443 (Extended One-Generation Reproductive Toxicity Study)
- Version / remarks:
- Without DNT and DIT modules
- Deviations:
- yes
- Remarks:
- 2 months pretreatment of F0; lifelong exposure of F1 to include investigation of carcinogenic potential
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Similar Substance 1
- IUPAC Name:
- Similar Substance 1
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: Charles-River CD
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories,Wilmington, MA, USA
- Age at study initiation: 38 days at beginning of F0-phase
- Weight at study initiation: F1 generation started exposure at weaning
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): 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): 12/12
Other: For F1-generation a maximum of two rats per sex from each litter were selected.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Diets were blended in a twin-shell blender.
DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Storage temperature of food: 20-21 °C and a humidity range aof 40-60%. - Details on mating procedure:
- Cohabitation
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Homogeneity and stability were analysed in the prepared diets before study initiation, weekly during the first 13 weeks of study and then monthly thereafter.
- Duration of treatment / exposure:
- 30 months F1 (plus in-utero phase) (with 10 animals per sex and dose for interim sacrifice after 12 months)
2 months (F0-generation) - Frequency of treatment:
- daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0.1 other: % in the diet
- Remarks:
- males 50 ± 18 mg/kg bw; females 62 ± 18 mg/kg bw
- Dose / conc.:
- 1 other: % in the diet
- Remarks:
- males 514 ± 179 mg/kg bw; females 631 ± 173 mg/kg bw
- Dose / conc.:
- 2 other: % in the diet
- Remarks:
- males 1072 ± 381 mg/kg bw; females 1319 ± 345 mg/kg bw
- No. of animals per sex per dose:
- 60 (F0)
70 (F1) - Control animals:
- yes, concurrent no treatment
- Details on study design:
- - Dose selection rationale: Based on existing repeated-dose toxicity data
Examinations
- Parental animals: Observations and examinations:
- Female rats were weighed an gestation days 0, 4, 14 and 21
Clinical signs, mortality - Oestrous cyclicity (parental animals):
- no
- Sperm parameters (parental animals):
- no
- Litter observations:
- from each litter, at least one rat was exposed for liftime and examined for systemic toxicity similart to OECD guideline 453
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations were morbidity, mortality and gross clinical signs
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly
BODY WEIGHT: Yes
- Time schedule for examinations: weekly through die first 14 weeks, biweekly for week 16-26 and monthly thereafter
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study) and mean daily diet consumption calculated as g food/kg body weight/day: Yes:
- Determined weekly through die first 14 weeks, biweekly for week 16-26 and monthly thereafter
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: yes
FOOD EFFICIENCY:
No data
OPHTHALMOSCOPIC EXAMINATION: Yes (after 3, 6, 12, 18 and 24 months af the chronic phase.)
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 3, 6, 12, 18 and 24 months and before termination
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes / No / No data
- How many animals: 10 per sex and dose group
- Parameters checked: haemoglobin, haematocrit, total eryrhrocyte count, total and differential leucocyte counts. and erythrocyte morphology
CLINICAL CHEMISTRY: Yes (3, 6, 12, 18 and 24 months and before termination)
aspartate aminatransferase, alanine aminotransferase, alkaline phosphatase, blood urea nitrogen, fasting glucose, total protein and creatinine
URINALYSIS: Yes (3, 6, 12, 18 and 24 months and before termination)
specific gravity, pH and presence of protein, glucose, ketones, bilirubin and occult blood, appearance (gross and microscopic)
NEUROBEHAVIOURAL EXAMINATION: No - Postmortem examinations (parental animals):
- no data
- Postmortem examinations (offspring):
- - Organ weights: brain, gonads, kidneys, liver, spleen and thyroid
HISTOPATHOLOGY: Yes (all animals trom the two control groups and from the high-dose (5.0%) group). Further groups were analysed in case of findings at the high dose groups.
Organs examined: adrenal (twa), aorta (abdominal), bone and marrow (femur). blood smear, brain (three sections: frontal cortex and basal ganglia. parietal cortex and thalamus. and cerebellum and pons), oesphagus. eye, (two. with optic nerve), heart (with coronar vesels), intestine (caecum, colon, duodenum and iLeum), kidneys (two). liver, lung and mainstem, subbronchi (lungs inflated with formalin), lymph nodes, mesenteric and mediastinal), mammary gland, (inguinal), nerve (sciatic). ovaries pancreas, pituitary, prostate, salivar gland (mandibular), seminal vesicles (two), skeietal muscle (biceps femoris), skin.spinal cord (cervical), spieen stomach, testes, with epididymides, tbymus. thyroid with parathyraid, trachea, urinary bladder (inflated with formalin), uterus, any tissue with gross changes of an uncertain nature together with an apparentdy normal section of thc same tissue, and any tissue masses or suspect tumours rogether with regional lymph nodes. - Statistics:
- The variances of thde two groups were tested tor equality using the F test (Gull 1978). lt the variances were equal, a standard independent two-sample test was used to -determiüne equality ot mneans. lt the variances differed, Welch's t-test was used to determine equal ity of means, using the Smith-Satterthwaite correction for unequal variances (Gill 1978). All tests were conducted at the 1.0% two-sided risk level. More detailed information is provided in Fd. Chem. Toxicol. 28, 221-234 (1990)
- Reproductive indices:
- fertility, gestation lengths, parturition, lactation
- Offspring viability indices:
- Number of live and stillborn pups
Pup survival through weaing
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- not specified
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- One female in die 0.1% group, one male and one female in the 1.0% group, and one male in die 2.0% group died.
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Organ weight findings including organ / body weight ratios:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Other effects:
- not specified
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 1 072 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed
Target system / organ toxicity (P0)
- Critical effects observed:
- no
Results: F1 generation
Details on results (F1)
The F1 generation developed normally during their lifetime. In females, exposure of 2% in the diet caused effects on body weight gain and survival rate after 90 - 102 weeks of treatment, males were not affected. F1 animals showed no histopathology findings in the gonads or other organs.
A specific target organ was not identified.
Effect levels (F1)
open allclose all
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- 631 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- body weight and weight gain
- Remarks on result:
- other: NOEL = 1% in the diet
- Remarks:
- No adverse effects on reproductive organs
- Dose descriptor:
- NOEL
- Generation:
- F1
- Effect level:
- >= 1 072 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: no adverse effects observed
- Remarks on result:
- other: NOEL = 2% in the diet
- Remarks:
- No adverse effects on reproductive organs
Target system / organ toxicity (F1)
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 1 319 mg/kg bw/day (actual dose received)
- System:
- other: none identified
- Organ:
- other: none identified
- Treatment related:
- yes
- Dose response relationship:
- yes
- Relevant for humans:
- not specified
Overall reproductive toxicity
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Executive summary:
The publication describes a life-time exposure dietary study that starts with in-utero exposure. For this purpose F0 rats (60 per sex and dose) were treateed for two months prior to mating with doses of 0.5, 1 and 2 % in the diet. The F1 generation (70 per sex and dose) was weaned onto the same diet and kept until the interim sacrifice after 12 months (10 per sex and dose), until their natural death or scheduled sacrife after 30 months.
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