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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 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
Endpoint summary
Administrative data
Description of key information
There were no adverse effects noted up to the highest dose levels tested
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 200 mg/kg bw/day
- Study duration:
- chronic
- 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 adverse effect observed
- Dose descriptor:
- NOAEL
- 25 mg/kg bw/day
- Study duration:
- chronic
- Species:
- mouse
Additional information
The following assessment was performed based on data from repeated dose toxicity tests with a FDA certified Indigo batch, commercial name: D&C Blue No. 6, which had to comply with the substance definition for certified batches.
Based on the specification for Indigo for use in medical devices as sutures as given under section 21CFR74.3106, the test substance definition for the certified batches used in these studies is the following:
Composition of D&C Blue No. 6 as given under section 21CFR74.3106
Constituent |
Concentration range |
Remarks |
2-(1,3-dihydro-3-oxo-2H-indol-2-ylidene)-1,2-dihydro-3H-indol-3-one EC no.: 207-586-9 |
>= 95.0 % (w/w) |
Total colour, not less than 95 % |
Aniline EC no.: 200-539-3 |
> 0.0 — <= 3.0 % (w/w) |
Volatile matter at 135 °C (275 °F), not more than 3 %. |
N-Methylaniline EC no.: 202-870-9 |
> 0.0 — <= 3.0 % (w/w) |
Volatile matter at 135 °C (275 °F), not more than 3 % |
Isatin |
> 0.0 — <= 0.3 % (w/w) |
|
Anthranilic acid |
> 0.0 — <= 0.3 % (w/w) |
|
Indirubin |
> 0.0 — <= 1.0 % (w/w) |
|
Lead (as Pb) |
> 0.0 — <= 10 ppm |
|
Arsenic (as As) |
> 0.0 — <= 3 ppm |
|
Mercury (as Hg) |
> 0.0 — <= 1 ppm |
|
Vat Indigo Potassium Salt is instable in an aqueous phase at neutral pH or as solid material on air and oxidises rapidly to Indigo (EC number 207-586-9). However, due to the production process of Vat Indigo, it contains a distinctly lower amount of aniline and methyl-aniline (see section 1.2 Impurities). Hence, the samples of the mentioned studies provide a worst-case scenario with respect to aniline and methyl-aniline and it is feasible to use these studies to assess the respective endpoints covered by these studies.
These studies consist of a 6-week repeat dose study in male rats conducted at dietary concentrations of up to 3% (2565 mg/kg bw/day),a 2-year chronic feeding study in male and female rats at dietary concentrations of up to 3% (1200 mg/kg bw/day),13-week range-finding study and 2-year feeding study in male and female beagle dogs at dietary concentrations of up to 3% (750mg/kg bw/day.
In the 6-week range finding study in male rats at 0, 0.1, 0.23, 0.55, 1.29 and 3% (mean daily test substance intake of about 0, 90, 199, 485, 1152, and 2565 mg/kg bw/day, calculated on an assumed body weight of 250 g and food consumption of 7% body weight) no adverse in-life effects were noted. Except for a faint colour retention in subcutaneous and peritoneal fat, no consistent gross alterations were found in the tissues or viscera. At microscopic examination, mild degenerative changes in the central zone of the liver lobules were seen in rats receiving 3.0% (2565 mg/kg bw/day) in the diet. Organ weights and ratios to body weight, physical appearance and behaviour of the test rats were comparable to controls
On the basis of the data of the 6-week range finding study, a 2-year chronic feeding study of the test substance was carried out with three groups of 25 male and 25 female adult albino rats and a control group of 80 males and 80 females. The dietary concentrations of 0, 0.25, 1.0 and 3.0% corresponded to the mean daily test substance intake of about 0, 100, 400, 1200 mg/kg bw/day in males and in females. Throughout the 2-year study, observations were made daily for mortality and weekly for gross signs of toxicity. Haematological values were determined and urinalyses made at 1, 3, 6, 12, 18 and 24 months. Necropsies were performed on all animals, which died during the study. At 12 months, five males and five females from each sacrificed animal in the control and high dose groups were examined microscopically. At the termination of the study, histopathology was performed on all preserved tissues from 10 male and 10 female rats in the control group and on an equal number in the high dosage group.
Clinical laboratory investigations revealed statistically significant bilirubinuria at 24 months in males and females at 1% and females at 3%. However, there were no corresponding histopathological findings. Furthermore, there were no relevant changes in organ weights, gross or microscopic pathology in rats given up to 1200 mg/kg bw/day orally in the diet for 2 years. The study appeared to demonstrate that after a period of adjustment to the higher dosage levels, the rats were able to tolerate up to 3% of this substance in their diets without serious adverse effects. The NOEL for repeated dose toxicity is considered to be 3% in food corresponding to about 1200 mg/kg/day.
In the 13 -week range finding study, one male and one female adult purebred beagle dogs were fed the test substance for 13 weeks at the 1.0% to 3.0% level in a basal laboratory diet of Wayne Dog Feed. The dosage was increased by 1.0% at 2-week intervals until the 3.0% level was reached. The dietary concentrations of 1.0 and 3.0 % corresponded to the mean daily test substance intake of about 250, and 750 mg/kg bw/day, calculated on an assumed body weight of 10 kg and daily total food consumption of 250 g. No toxicological relevant findings were observed after 13 weeks administration of 3% (ca. 750 mg/kg bw/day) indigo in the diet.
Based on the results of the 13-week feeding study, 3 groups of 3 male and 3 female young adult purebred beagle dogs and a control group of 10 males and 10 females were fed a basal diet of Wayne Dog Feed containing the test substance at dosage levels of 0, 0.25, 1 and 3% for two years. These dietary corresponded to the mean daily test substance intake of about 0, 62.5, 250, and 750 mg/kg bw/day, calculated on an assumed body weight of 10 kg and daily total food consumption of 250 g. The dogs were observed daily for signs of toxic or pharmacologic effects. Haematological and biochemical studies and urinalyses were performed at the start and at 1, 3, 6, 12, 18 and 24 months. All survivors were sacrificed at 24 months for necropsies. Chronic exposure to the test substance resulted in no toxicologically significant effects on survival rates, behaviour, body weights or weight gains, organ weights, or in haematology, clinical chemistry, or urinalysis parameters. No gross pathological or histopathological findings related to the test substance exposures were observed up to 3% test substance in the diet (750 mg/kg bw/day). Based on the results of the study, 750 mg/kg bw/day is considered to be the no-observed-effect-level (NOEL) for the test substance in dogs of both sexes.
Justification for classification or non-classification
Test substance is practically non-toxic, no classification necessary.
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.