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EC number: 240-005-7 | CAS number: 15876-39-8
- 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: dermal
Administrative data
- Endpoint:
- repeated dose toxicity: dermal, other
- Remarks:
- Combined repeated dose & carcinogenicity
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Justification for type of information:
- Data is from peer reviewed publication
Data source
Reference
- Reference Type:
- publication
- Title:
- Skin Painting Studies In Mice With 14 FD & C And D & C Colors: FD & C Blue No. 1, Red No. 3 & Yellow No. 5, D & C Red No. 7, Red No. 9, Red No. 10, Red No. 19, Red No. 2 1 , Red No. 27, Red No. 31, Red No. 36, Orange No. 5, Orange No. 10 & Orange No 17
- Author:
- Steven Carson
- Year:
- 1 984
- Bibliographic source:
- J. Toxicol. Cut. & Ocular Toxicol. 3(4), 357-370 (1984)
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 by the dermal route was performed to determine the dermal toxic nature of the test compound 2',4',5',7'-Tetrabromofluorescein upon repeated application.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 2',4',5',7'-Tetrabromofluorescein
- IUPAC Name:
- 2',4',5',7'-Tetrabromofluorescein
- Reference substance name:
- 2-(3,6-dihydroxy-2,4,5,7-tetrabromoxanthen-9-yl)-benzoic acid
- EC Number:
- 239-138-3
- EC Name:
- 2-(3,6-dihydroxy-2,4,5,7-tetrabromoxanthen-9-yl)-benzoic acid
- Cas Number:
- 15086-94-9
- Molecular formula:
- C20H8Br4O5
- IUPAC Name:
- 2-(2,4,5,7-tetrabromo-3,6-dihydroxy-9H-xanthen-9-yl)benzoic acid
- Test material form:
- solid
- Details on test material:
- - Name of test material (as cited in study report): D & C Red no. 21
- Molecular formula: C20H8Br4O5
- Molecular weight: 647.8942 g/mol
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): 98% pure
Constituent 1
Constituent 2
- Specific details on test material used for the study:
- - Name of test material: D & C Red no. 21
- Molecular formula: C20H8Br4O5
- Molecular weight: 647.8942 g/mol
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): 98% pure
Test animals
- Species:
- mouse
- Strain:
- ICR
- Remarks:
- Swiss Webster derived
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Fasting period before study: No data available
- Housing: Each animal was assigned an identification number and individually housed in a supported wire cage.
- Diet (e.g. ad libitum): No data available
- Water (e.g. ad libitum): No data available
- Acclimation period: No data available
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- other: Distilled water
- Details on exposure:
- TEST SITE
- Area of exposure: 6 cm²
- % coverage: No data available
- Type of wrap if used: No data available
- Time intervals for shavings or clipplings: Subsequent periodic clipping was performed according to the rate of hair growth
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data available
- Time after start of exposure: No data available
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml of the vehicle containing 140.1 mg test material
- Concentration (if solution): 0.1ml
- Constant volume or concentration used: yes
- For solids, paste formed: no data available
VEHICLE
- Justification for use and choice of vehicle (if other than water): No data available
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 140.1 mg
- Lot/batch no. (if required): Not data
- Purity: no data available
USE OF RESTRAINERS FOR PREVENTING INGESTION: no data - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data available
- Duration of treatment / exposure:
- 18 months/ 473 days
- Frequency of treatment:
- Twice weekly
Doses / concentrations
- Remarks:
- Doses / Concentrations: 140.1 mg
- No. of animals per sex per dose:
- Total: 500
140.1 mg: 50/sex
0 mg/Kg bw: 150/sex
Positive control: 150/sex - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data available
- Positive control:
- 3,4-benzpyrene
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked in table [No.?] were included. Mortality and morbundity
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twice weekly gross toxicity was noted
BODY WEIGHT: no data
- Time schedule for examinations: no data
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): no data
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
FOOD EFFICIENCY: No data
- 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:
- Dose groups that were examined: No data
HAEMATOLOGY: No data
- Time schedule for collection of blood: No data
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: No data
- Parameters checked in table [No.?] were examined.
DERMAL IRRITATION (if dermal study): No data
- Time schedule for examinations: No data
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.
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.
NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: No data sensory activity / grip strength / motor activity / other: No data
OTHER: - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Animals that died, those sacrificed moribund, and those surviving the 18-month experimental period were necropsied. Tissues from following organs were collected: the brain, pituitary, thyroid, thymus, liver, spleen, kidney, adrenal, stomach, small intestines, large intestines, urinary bladder, axillary lymph nodes, testes, ovary, skin from area of treatment, any tissue masses, grossly abnormal organs, or other tissues.
HISTOPATHOLOGY: Yes, Tissues selected for histopathology were sectioned, stained with hematoxylin and eosin and was examined by a pathologist. The following tissues were selected for examination: skin and any grossly abnormal organs and tissues of all animals in the color experimental groups; skin and any grossly abnormal organs and tissues of approximately 50 vehicle control animals. complete pathology on five males and five females randomly selected vehicle control animals that survived the 18-month experimental period; and complete pathology on five males and five females randomly selected vehicle control animals that survived the 18-month experimental period; and complete pathology of five male and five female animals from the positive control group that included induced skin lesions. - Other examinations:
- No data available
- Statistics:
- No data available
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Dermal irritation:
- not specified
- Mortality:
- mortality observed, treatment-related
- Body weight and weight changes:
- not specified
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not specified
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- effects observed, treatment-related
- Other effects:
- not specified
- Details on results:
- Clinical signs and mortality:
Clinical signs: No data
Mortality: The percent survival of the treated mice changed with the duration of the treatment. The survival was 97% in 4 months, 93% in 10 months, 68% in 12 months and 50% in 18 months respectively.
Dermal irritation: No data
Body weight and weight gain: No data
Food consumption and compound intake: No data
Food efficiency: No data
Water consumption and compound intake: No data
Opthalmoscopic examination: No data
Haematology: No data
Clinical chemistry: No data
Urinanalysis: No data
Neurobehaviour: No data
Organ weights: No data
Gross pathology: No data
Histopathology: The incidence of extramedullary hematopoesis of the spleen (5 male and 5 females: 10%) in the test group was consistent with that found in the distilled water vehicle control groups. The incidence in the three distilled water control groups was 13 % , 18 % , and 22 % for a mean of 17.7 % . The test group did not show a greater incidence than a control group.
The incidence of ectoparasitism was greater in the dye treated group than found in the vehicle controls. This increase in skin mite infestation may have contributed to the increase in epidermal change dermatitis, acanthosis, and hyperkeratosis observed in the dye treated groups.
Although the number of neoplasias involving the mammary glands or internal organs was noted in the test group, there was, however, no apparent change in their pattern which could be attributed to the dermal application of the test dye compound.
The incidence and severity of lesions of interstitial nephritis, cystitis, amyloidosis, and bronchopneumonia though observed in the test groups but there were no significant variations that could be attributed to application of the test compound.
Effect levels
- Dose descriptor:
- NOAEL
- Effect level:
- 140.1 other: mg
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- gross pathology
- histopathology: neoplastic
- histopathology: non-neoplastic
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table: Percent survival
Months |
5 |
10 |
16 |
18 |
D & C Red no 21 |
97 |
93 |
68 |
50 |
Table: Details of microscopic analysis
Animal Number |
Experimental Days Observed |
Location of Lesion |
Microscopic Diagnosis |
7F |
532 |
Swelling in left in-guinal area |
Mammary gland adenocarcinoma |
47F |
557 |
Swelling in left hindleg |
Hemangiosarcoma |
54M |
558 |
Nodule in liver and heart |
Liver-hypertrophic nodules heart-organizing thrombus in left atrium |
61M |
558 |
Tissue mass in liver |
Hepatic cell adenoma |
73M |
558 |
Tissue mass in liver |
Hepatic cell adenoma |
84M |
558 |
Tissue mass in liver and nodule in kidney |
Liver-hepatic cell adenoma kidney-moderately severe interstinal nephritis |
87M |
558 |
Tissue mass in liver |
Hepatic cell adenoma |
94M |
558 |
Tissue mass in liver |
Hypertrophic nodule |
Applicant's summary and conclusion
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) for the test compound 2',4',5',7'-Tetrabromofluorescein is considered to be 140.1 mg when ICR mice were exposed with the test compound for 473 days.
- Executive summary:
Combined repeated dose & carcinogenicity by the dermal route was performed to determine the dermal toxic nature of the test compound 2',4',5',7'-Tetrabromofluorescein upon repeated application. The test chemical was applied to the clipped dorsal area mice. The animals were observed for mortality, clinical signs and gross pathology and histopathology was performed. The percent survival of the treated mice changed with the duration of the treatment. The survival was 97% in 4 months, 93% in 10 months, 68% in 12 months and 50% in 18 months respectively. The incidence of extramedullary hematopoesis of the spleen (5 male and 5 females: 10%) in the test group was consistent with that found in the distilled water vehicle control groups. The incidence in the three distilled water control groups was 13 % , 18 % , and 22 % for a mean of 17.7 % . The test group did not show a greater incidence than a control group. The incidence of ectoparasitism was greater in the dye treated group than found in the vehicle controls. This increase in skin mite infestation may have contributed to the increase in epidermal change dermatitis, acanthosis, and hyperkeratosis observed in the dye treated groups. Although the number of neoplasias involving the mammary glands or internal organs was noted in the test group, there was, however, no apparent change in their pattern which could be attributed to the dermal application of the test dye compound. The incidence and severity of lesions of interstitial nephritis, cystitis, amyloidosis, and bronchopneumonia though observed in the test groups but there were no significant variations that could be attributed to application of the test compound. Based on the observations made, the No Observed Adverse Effect Level (NOAEL) for the test compound 2',4',5',7'-Tetrabromofluorescein is considered to be 140.1 mg when ICR mice were exposed with the test compound for 473 days.
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