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EC number: 431-920-4 | CAS number: -
- 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
- Remarks:
- other: 15 and 64 applications
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 965
- Report date:
- 1965
- Reference Type:
- publication
- Title:
- Toxicology of Indigo - a review
- Author:
- Ferber KH
- Year:
- 1 987
- Bibliographic source:
- J. Environ. Pathol. Toxicol. Oncol. 7, 73 -84 (1987)
Materials and methods
- Principles of method if other than guideline:
- U.S. FDA 1962-1973
- GLP compliance:
- no
- Limit test:
- no
Test material
- Reference substance name:
- Indigo
- IUPAC Name:
- Indigo
- Details on test material:
- - Name of test material (as cited in study report): D&C Blue 6
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Weight at study initiation: 1.6 to 2.7 kg
- Fasting period before study: -
- Housing: single
- Diet: Purina Rabbit Chow ad libitum
- Water: tap water ad libitum
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- other: 1. white petrolatum USP XVI, 2. Ointment hydrophilic USP XVI
- Details on exposure:
- TEST SITE
- Area of exposure: abdominal skin - application of ointment with gentle inunction
- Pre-treatment of skin: 1. shaved
2. shaved and abraded
- Type of wrap if used: loose gauze and adhesive tape binder
- Time intervals for shavings or clipping: periodically
- Abrasion: weekly by hypodermic needle
- Removal of binders: 18 to 20 hours after application
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g/kg bw
- Concentration: 0.1% and 1% in ointments
- Constant volume or concentration used: constant concentration, variable volume
VEHICLE
- Justification for use and choice of vehicle: test item is insoluble in water
1. white petrolatum USP XVI
2. Ointment hydrophilic USP XVI
- Amount(s) applied (volume or weight with unit): 0.5 g/kg bw
- Concentration (if solution): -
- Lot/batch no. (if required): -
- Purity: USP
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes - Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- NA
- Duration of treatment / exposure:
- 15 applications 5 days/week: 21 days
64 applications 5 days/week: 90 days - Frequency of treatment:
- 5 days/week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0.5 and 5 mg/kg bw
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 15 applications - shaved: 3 rabbits
15 applications - abraded: 3 rabbits
64 applications - shaved: 3 rabbits - Control animals:
- yes, concurrent vehicle
- Details on study design:
- 1. Formulation ointment based on White Petrolatum USP XVI
2. Formulation based on Ointment Hydrophilic USP XVI
Supplier of White Petrolatum USP XVI, Ointment Hydrophilic USP XVI, and the 0.1% and 1% test item formulations in both vehicles was E.R. Squibb and Sons.
3 or 4 days treatment free period after last application - Positive control:
- NA
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily
BODY WEIGHT: Yes
- Time schedule for examinations: prior to each application
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior first dosing and
3-week phase: 24 hours after the 12th, 13th or 14th application
13-week phase: 24 hours after the 18th or 19th application and on the day of the 62nd or 63rd application
- Anaesthetic used for blood collection: No data
- Animals fasted: No
- How many animals: all
- Sampling site: marginal ear vein
- Parameters examined: erythrocyte counts, total and differential leukocyte counts, hematocrit, hemoglobin
URINALYSIS: Yes
- Time schedule for collection of blood: prior first dosing and
3-week phase: 24 hours after the 12th, 13th or 14th application
13-week phase: 24 hours after the 18th or 19th application and on the day of the 62nd or 63rd application
- Metabolism cages used for collection of urine: No - catheterization
- Animals fasted: No
- Parameters examined: appearence, pH, specific gravity, glucose, acetone, protein, bilirubin, occult blood, microscopic examination of sediment
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
- Organs preserved: brain, thyroid, lungs, heart, liver, kidneys, adrenals, skin, bone marrow, macroscopic lesions
- Microscopic investigation: all preserved tissues
- Animals: all
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Dermal irritation:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
6 of the 54 rabbits dies during the study:
- Control group
- WP: after the 8th, 28th 35th application (3)
- HO: after the 8th application (1)
- Treatment groups
- 0.1% in HO: after the 29th application (1)
- 1% in WP: after the 34th application (1)
These deaths were attributed to coincidal mucoid colitis and not related to dermal application of the test substance.
DERMAL IRRITATION
There was no dermal irritation attributable to the color. The signs of irritation noted (slight erythema, atonia, slight desquamation) were considered the results of the vehicles and the technique of application.
The application sites were bluish stained by the test substance.
BODY WEIGHT AND WEIGHT GAIN
-
HAEMATOLOGY
-
URINALYSIS
-
GROSS PATHOLOGY
-
HISTOPATHOLOGY
-
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 5 mg/kg bw/day
- Sex:
- male/female
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The repeated dermal administration of the 0.1% and 1% test substance formulations to New Zealand white rabbits at the rate of 500 mg/kg bw/day (5 days/week) to the intact and abraded skin of animals of both sexes, for up to 13 weeks, resulted in no test substance-related deaths, clinical signs or skin irritation. No adverse effects were noted in clinical laboratory investigations, macroscopical or microscopical evaluations. Consequently, the NOAEL for dermal application to rabbit skin was 5 mg/kg bw/day.
- Executive summary:
There are no repeated dose toxicity tests with the notified substance. However, Produkt 1998 is oxidized within 5 to 15 minutes to indigo in presence of moisture and oxygen. The present study was performed based on data from repeated dose toxicity tests with Indigo (CAS-Nr. 482-89-3), commercial name: D&C Blue No. 6, certified by U.S. FDA (for coloring surgical sutures). The test substance was applied at an amount of 500 mg/kg bw/day of an 0.1% and 1% ointment formulation, 5 days per week to the intact and abraded skin of male and female New Zealand white rabbits according to the following protocol matrix:
No. of applications
Test material
No. of animals
Skin Intact
Skin Abraded
(m/f)
(m/f)
(m/f)
15
WP
3/3
2/1
1/2
15
0.1% in WP
2/4
1/2
1/2
15
1% in WP
4/2
2/1
2/1
15
HO
4/2
2/1
2/1
15
0.1% in HO
2/4
1/2
1/2
15
1% in HO
4/2
2/1
2/1
64
WP
2/1
2/1
-
64
0.1% in WP
2/1
2/1
-
64
1% in WP
2/1
2/1
-
64
HO
1/2
1/2
-
64
0.1% in HO
2/1
2/1
-
64
1% in HO
1/2
1/2
-
m: male; f: female; WP: White petrolatum; HO: Hydrophilic ointment
Weight trends, mortality and signs of systemic toxicity and dermal irritation were recorded. Blood counts and urinalyses were performed on all animals at the start and termination of the study. Additional samples were taken during the fourth weeks from those animals tested for 13 weeks (64 applications). All animals were subjected at autopsy or death or terminal sacrifice. Tissues examined microscopically were: brain, thyroid, lung, heart, liver, kidneys, adrenals, skin, and bone marrow.
The repeated dermal administration of the 0.1% and 1% test substance formulations to New Zealand white rabbits at the rate of 500 mg/kg bw/day (5 days/week) to the intact and abraded skin of animals of both sexes, for up to 13 weeks, resulted in no test substance-related deaths, clinical signs or skin irritation. No adverse effects were noted in clinical laboratory investigations, macroscopical or microscopical evaluations. Consequently, the NOAEL for dermal application to rabbit skin was 5 mg/kg bw/day.
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.
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