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EC number: 204-934-1 | CAS number: 129-17-9
- 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
Repeated Dose toxicity (Oral): The No observed adverse effect level taken from a peer reviewed publication is reported to be 375 mg/kg bw when rats were repeatedly exposed to the test chemical (C.I. Food Blue 3) for a 90 day period.
Repeated Dose toxicity (Inhalation): The estimated vapour pressure of the chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt is very low i.e. 1.145239e-31 Pascal. With such low vapour pressure, repeated exposure by the inhaltion route is highly unlikely. Thus, this end point was considered for waiver since no adverse effect by this route are expected.
Repeated dose toxicity (Dermal): The chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt (Synonym C.I. Food Blue 3) is dominantly used as a food color. THus, repeated exposure by the dermal route is highly unlikely. Hence this end point was considered for waiver since no adverse effect by this route are expected..
Key value for chemical safety assessment
Repeated dose toxicity: via oral route - systemic effects
Link to relevant study records
- Endpoint:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed journal
- Qualifier:
- according to guideline
- Guideline:
- other: Data is from Journal with permission
- Principles of method if other than guideline:
- Chronic repeated dose toxicity was studied for Blue VRS in rats orally.
- GLP compliance:
- no
- Species:
- rat
- Strain:
- other: SPF Carworth Farm E
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Details on test animalTEST ANIMALS- Source: No data available- Age at study initiation: No data available- Weight at study initiation: No data available- Fasting period before study: No data available- Housing: 5/cage- Diet (e.g. ad libitum): Spillers Small Laboratory Animal diet, ad libitum- Water (e.g. ad libitum): Water ad libitum- Acclimation period: No data availableENVIRONMENTAL CONDITIONS- Temperature (°C): No data available- Humidity (%):No data available- Air changes (per hr): No data available- Photoperiod (hrs dark / hrs light): No data availableIN-LIFE DATES: From: To: No data available
- Route of administration:
- oral: feed
- Vehicle:
- other: Spillers Small Laboratory Animal diet
- Details on oral exposure:
- Details on oral exposurePREPARATION OF DOSING SOLUTIONS: No data availableDIET PREPARATION- Rate of preparation of diet (frequency): Daily - Mixing appropriate amounts with (Type of food): Spillers Small Laboratory Animal food - Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): Spillers Small Laboratory Animal diet - Concentration in vehicle: 0.0, 0.3, 0.75, 1.5 and 3.0% - Amount of vehicle (if gavage): No data available- Lot/batch no. (if required): No data available- Purity: No data available
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- No data
- Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- Daily
- Remarks:
- Doses / Concentrations:0.0, 0.3, 0.75, 1.5 and 3.0 % (0, 150, 375, 750 and 1500 mg/kg/day)Basis:nominal in diet
- No. of animals per sex per dose:
- Total : 1800 % : 15 male and 15 female 0 % : 15 male and 15 female003 % : 15 male and 15 female0.75 % : 15 male and 15 female1.5 % : 15 male and 15 female3.0 % : 15 male and 15 female
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
- Observations and examinations performed and frequency:
- Observations and examinations performed & frequencyCAGE SIDE OBSERVATIONS: Yes - Time schedule: Daily - Cage side observations checked in table [No.?] were included: Mortality were observed DETAILED CLINICAL OBSERVATIONS: Yes - Time schedule: Daily BODY WEIGHT: Yes - Time schedule for examinations: WeeklyFOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes- 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 available WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available - Time schedule for examinations: No data available OPHTHALMOSCOPIC EXAMINATION: No data available - Time schedule for examinations: No data available - Dose groups that were examined: No data available HAEMATOLOGY: Yes- Time schedule for collection of blood: Weekly At 6 week and on terminally - Anaesthetic used for blood collection: Cardiac puncture No data available - Animals fasted: No data- How many animals: All the treated animals were examined. - Parameters checked in table [No.?] were examined: Erythrocytes, Packed cell volume, Hemoglobin concentration in all teeated animals and total and Dtfferentlal Leucocytes count in 0, 1.5 and 3.0 % dose groups were examined. CLINICAL CHEMISTRY: Yes - Time schedule for collection of blood: At 6 week and on terminally - Animals fasted: No data available - How many animals: All the treated animals were examined. - Parameters checked in table [No.?] were examined: Serum urea was examined. URINALYSIS: Yes - Time schedule for collection of urine: at week 12, a 6-hr period of water deprivation and during a 4-hr period beginning 16 hr after a water load of 25 ml/kg. - Metabolism cages used for collection of urine: : No data available - Animals fasted: : No data available - Parameters checked in table [No.?] were examined: pH, Specific gravity and Volume were examined. NEUROBEHAVIOURAL EXAMINATION: No data available - Time schedule for examinations: No data available - Dose groups that were examined: No data available - Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available OTHER:Absolute and relative organ weights were examined.Organ examined. Liver, Left and Right Kidneys, Brain, Heart, Spleen, Adrenals and Gonads were examined.
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes Gross abnormalities were examined. HISTOPATHOLOGY: YesOrgan examined. Liver, Left and Right Kidneys, Brain, Heart, Spleen, Adrenals and Gonads were examined.
- Other examinations:
- No data available
- Statistics:
- No data available
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Mortality: No effect on servival were observed in treated rat as compared to control. Clinical signs: No effect were observed on health of treated rat as compared to control.
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mortality: No effect on servival were observed in treated rat as compared to control. Clinical signs: No effect were observed on health of treated rat as compared to control.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Impairment of growth was observed in male rats during the first 4 weeks in 1.5 and 3.0 % dose group.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Food consumption: Reduced food intake was observed in 1.5 and 3.0 % treated rats. Compound intake: Reduced in compound intake was observed in 1.5 and 3.0 % treated rats.
- Food efficiency:
- not specified
- Description (incidence and severity):
- Reduced
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- No departure from normality was observed; red cell morphology was also unaffected.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- No effect on kidney function investigated during the last week of treatment or on serum urea nitrogen determined terminally
- Urinalysis findings:
- effects observed, treatment-related
- Description (incidence and severity):
- The urine of all the animals receiving Blue VRS in the diet was bluish-green and slightly more acid than that of the controls. Proteinurea was comparable in test and control groups and no reducing substances were detected in the urine of any group.
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- No effect on the absolute or relative (g/100 g body weight) organ weights was observed
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Fatty changes in the liver of 1.5 and 0.3 % treated female rat were observed.
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Histopathology:Increase number of active acini in the thyroids of 1.5 & 0.3% treated male and female rats were observed. Blue material in the lumen of convoluted tubules associated with a coloured line observed at the cortlcomedullary junction of kidney in male of 3.0% treated dose group. Retardation of growth in males at the 1.5 and 3.0 % dose group and occasional fatty change in the livers of some of the females at the 3.0 % dose group. Increase in the number of active follicles in the thyroids of both males and females of the treated groups but this is not necessarily attributable to Blue VRS. Histological changes associated with acinal activity occur in response to stress of various kinds.
- Dose descriptor:
- NOAEL
- Effect level:
- 375 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effect on survival, clinical sign, body weight, food consumption, compound intake, haematology, clinical chemistry, organ weights, gross pathology and histopathology.
- Critical effects observed:
- not specified
- Conclusions:
- The no-observed-adverse-effect-level (NOAEL) was considered to be 375 mg/kg/day (0.75 %) when SPF Carworth Farm E male and female rats were treated with Blue VRS.
- Executive summary:
In a Chronic repeated dose toxicity study, SPF Carworth Farm E male and female rats were treated with Blue VRS at a concentration of 0.0, 0.3, 0.75, 1.5 and 3.0 % (0, 150, 375, 750 and 1500 mg/kg/day) orally. Impairment of growth, Reduction in food consumption, compound intake and bluish-green and slightly more acid urine were observed in 1.5 and 3.0 % treated male and female as compared to control. In addition, Fatty changes in the liver of female rat and increase number of active acini in the thyroids of male rat of 1.5 and 3.0 % treated animals. Blue material in the lumen of convoluted tubules associated with a coloured line observed at the cortcomedullary junction of kidney in male of 3.0 % treated dose groups but this was not necessarily attributable to Blue VRS. Histological changes associated with acinal activity occur in response to stress of various kinds were noted. Therefore, the no observed adverse effect level (NOAEL) was considered to be 375 mg/kg/day (0.75 %) when SPF Carworth Farm E male and female rats were treated with Blue VRS orally for 90 days.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 375 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Data from K2 publication.
Repeated dose toxicity: inhalation - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: inhalation
- Data waiving:
- exposure considerations
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Repeated dose toxicity: inhalation - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Repeated dose toxicity: dermal - systemic effects
Link to relevant study records
- Endpoint:
- repeated dose toxicity: dermal
- Data waiving:
- exposure considerations
- Justification for data waiving:
- other:
- Critical effects observed:
- not specified
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
Repeated dose toxicity: dermal - local effects
Endpoint conclusion
- Endpoint conclusion:
- no study available
Additional information
Repeated dose toxicity: oral
Various publications were reviewed to determine the toxic nature of the test compound Blue VRS upon repeated application by the oral route of exposure. The studies ate reviewed as below:
In a Chronic repeated dose toxicity study by Hall et al (1967), SPF Carworth Farm E male and female rats were treated with Blue VRS at a concentration of 0.0, 0.3, 0.75, 1.5 and 3.0 % (0, 150, 375, 750 and 1500 mg/kg/day) orally. Impairment of growth, Reduction in food consumption, compound intake and bluish-green and slightly more acid urine were observed in 1.5 and 3.0 % treated male and female as compared to control. In addition, Fatty changes in the liver of female rat and increase number of active acini in the thyroids of male rat of 1.5 and 3.0 % treated animals. Blue material in the lumen of convoluted tubules associated with a coloured line observed at the cortcomedullary junction of kidney in male of 3.0 % treated dose groups but this was not necessarily attributable to Blue VRS. Histological changes associated with acinal activity occur in response to stress of various kinds were noted. Therefore, the no observed adverse effect level (NOAEL) was considered to be 375 mg/kg/day (0.75 %) when SPF Carworth Farm E male and female rats were treated with Blue VRS orally for 90 days.
Based on the SSS QSAR prediction (2016) done for repeated dose toxicity via oral route, the NOAEL value is estimated to be 615.1199 mg/kg bw/d for 24 months daily exposure for the test compound hydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium salt on rats. Thus based on this value it can be concluded that hydrogen [4-[4-(diethylamino)-2', 4’-disulphonatobenzhydrylidene] cyclohexa-2, 5-dien-1-ylidene]diethylammonium, sodium salt is not very toxic in nature via oral route of exposure and hence is not likely to classify as an repeated oral toxicant.
In a Combined repeated dose & carcinogenicity study (EFSA Panel, 2013), male and female mice were treated with Patent Blue V at a concentration of 0, 0.1, 0.3 and 1 % (equivalent to 0, 150, 500 and 1500 mg/kg body weight/day) orally. Slightly increased in mortality, significant decrease in body weight of male mice and significant reduction in haemoglobin, haematocrit, red blood cell counts and reticulocyte count, increase in the total number of white blood cells in male and female rat were observed at 1 % dose group as compared to control. Increase in relative heart and caecal weights were observed in female at 1 % dose group. In addition, non-neoplastic lesions of lungs, kidneys and liver were observed. Adrenocortical adenoma and carcinoma, adenoma of mammary gland were noted and were found to be dose independent. The observed changes were mainly isolated findings, of commonly occurring tumours showing no dose-response relationship. Therefore, NOAEL was considered to be 0.3 % (500 mg/kg body weight /day) when male and female mice were treated with Patent Blue V orally for 32 weeks.
Repeated dose toxicity: Inhalation
The estimated vapour pressure of the chemical hydrogen [4 -[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt is very low i.e. 1.145239e-31 Pascal. With such low vapour pressure, repeated exposure by the inhaltion route is highly unlikely. Thus, this end point was considered for waiver.
Repeated dose toxicity: Dermal
The chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt (Synonym C.I. Food Blue 3) is dominantly used as a food color. Thus, repeated exposure by the dermal route is highly unlikely. Hence this end point was considered for waiver.
On the basis of the available data and the applied waivers, the test chemical is not likely to classify as a toxicant upon repeated exposure by the oral, dermal and inhalation route of exposure.
Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
The no-observed-adverse-effect-level (NOAEL) was considered to be 375 mg/kg/day (0.75 %) when SPF Carworth Farm E male and female rats treated with Blue VRS.
Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
The estimated vapour pressure of the chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt is very low i.e. 1.145239e-31 Pascal. With such low vapour pressure, repeated exposure by the inhaltion route is highly unlikely. Thus, this end point was considered for waiver.
Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The chemical hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt (Synonym C.I. Food Blue 3) is dominantly used as a food color. Thus, repeated exposure by the dermal route is highly unlikely. Hence this end point was considered for waiver.
Justification for classification or non-classification
Based on the available data and the applicable waivers, it can be concluded that the chemical C.I. Food Blue 3 is not likely to cause repeated dose toxicity by the oral, inhalation or dermal route of exposure. Thus, the chemical was not considered for classification.
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