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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 231-494-8 | CAS number: 7585-41-3
- 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: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- September 21,1993 - November 24,1993
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 993
- Report date:
- 1993
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- March 22, 1990
- Deviations:
- no
- Remarks:
- Urinalysis not performed
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate
- EC Number:
- 226-109-5
- EC Name:
- Calcium 3-hydroxy-4-[(4-methyl-2-sulphonatophenyl)azo]-2-naphthoate
- Cas Number:
- 5281-04-9
- Molecular formula:
- C18H14N2O6S.Ca
- IUPAC Name:
- calcium 3-hydroxy-4-[(4-methyl-2-sulfonatophenyl)diazenyl]-2-naphthoate
- Test material form:
- solid: nanoform
- Details on test material:
- - D&C Red 7
- Analytical purity: 98% w/w
- R-92-214
Test materials used in this dossier are all considered to fall under the definition of nano-materials according to the European Commission Recommendation 2011/696/EU as the synthesis and manufacturing of this pigment always yields particulate material with a fine particle size distribution.
Constituent 1
- Specific details on test material used for the study:
- -Analytical purity : 98 % w/w
Test animals
- Species:
- rat
- Strain:
- Crj: CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- - Sources:Charles River Laboratories Japan (Atsugi Breeding Center)
- Age at study initiation : 7 weeks
- Weight at study initiation : females 196.5-227.4 g, males: 235.5-299.6 g
- Housing : Individually housed in stainlelss suspended cages
- Diet : CA-1 (CLEA Japan, Inc.) ad libitum
- Water : Tap water, ad libitum
- Acclimation period : 1 week for quarantine and acclimaition
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 5% gum arabic solution
- Details on oral exposure:
- - Amount of vehicleL 10 mL/kg
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration of test substance in the dosing formulation was analytically confirmed to attain the required level.
- Duration of treatment / exposure:
- Males : Total of 42 days ( 14 days before mating, 14 days for mating, and 14 days after mating)
Females : Total of 41-50 days (14 days before mating, during mating, pregnancy and up to lactation day 3) - Frequency of treatment:
- Daily
Doses / concentrationsopen allclose all
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 300 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 13/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: doses were selected on the basis of a 14-day preliminary repeat dose study at 1000 mg/kg bw/day. No deaths and clinical signs observed. 3 cases of necrosis or regeneration of tubular epithelium were seen in males.
Examinations
- Observations and examinations performed and frequency:
- DETAILED CLINICAL OBSERVATIONS: Yes (see table 1&2)
- Time schedule: Males and Females - on each administration day.
BODY WEIGHT: Yes
- Time schedule for examinations: Males - measured once a week on administration days 0, 7, 14, 21, 28, 35, and 42; Females - measured once a week on administration days 0, 7, 14, and 21, during pregnancy on days 0, 7, 14, and 20, during lactation on day 0 and 4.
FOOD CONSUMPTION AND COMPOUND INTAKE :
- Food consumption for each animal determined: Yes
- Time schedule for examinations : Males - measured once a week on administration days 0, 7, 14, 21, 28, 35, and 42; Females - measured once a week on administration days 0, 7, 14, and 21, during pregnancy on days 0, 7, 14, and 20, during lactation on day 0 and 4.
OPHTHALMOSCOPIC EXAMINATION: No
- Time schedule for examinations:
- Dose groups that were examined:
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Males - day after final administration day
- Anaesthetic used for blood collection: Yes (pentobarbital)
- Animals fasted: No data
- How many animals: 13 animals per male per group
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Males - day after final administration day
- Anaesthetic used for blood collection: Yes (pentobarbital)
- Animals fasted: No data
- How many animals : 13 animals per male per group
- Parameters checked in table 2 were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table 3 under 'Any other information on results incl. tables')
HISTOPATHOLOGY: Yes (see table 4 under 'Any other information on results incl. tables') - Statistics:
- x squared test was conducted for copulation and fertility indices. For all the other parameters, Bartlett's test was used to examine uniformity of distribution in each group, and one-way statistical analysis was performed when the distribution is uniform. Where significant differences were observed, Dunnett's test or Scheff's test was performed to examine differences in averages between each test group and control groups. Kruskal-Wallis's test was conducted when the distribution was not uniform. Significant testing was carried out at the 5% and the 1% levels.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- - Males: red stained feces at all doses. One animal with crust formation during whole treatment period at 100 mg/kg bw/day.
- Females: red stained feces at all doses. One animal with crust formation from day 22 to sacrifice at 1000 mg/kg bw/day. - Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Males - 1 day after termination of administration period: Significantly lower values of MCH (p<0.05) were seen in the 300 and 1000 mg/kg bw/day groups compared to the controls. Dose-dependent decrease in WBC was seen in the the 300 and 1000 mg/kg bw/day groups, but the effects were not significant. In the absence of historical control data, no corresponding histopathology findings and other affected parameters, the findings are considered of no biological relevance.
- Clinical biochemistry findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Males - 1 day after termination of administration period: Significantly lower levels of inorganic phosphorus and Calcium were seen in the 300 mg/kg bw/day group. Significant low levels of Total cholesterol and pottasium and significant high values of Chloride and GOT were noted in the 1000 mg/kg bw/day group.
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- Males - 1 day after termination of administration period: Significant high values of relative weight of kidney were observed in the 1000 mg/kg bw/daygroup.
Females - Day 4 of lactation: Significant low values of absolute and relative weight of thymus were noted in the 100 mg/kg kw/day group (p< 0.01 for absolute weight, p<0.05 for relative weight). Significant low values of absolute weight of thymus were noted in the 1000 mg/kg bw/day group (p <0.05).
Females sacrificed at pregnancy Day 25: Non-significant low values of absolute and relative weight of thymus were noted in one animal with total litter loss in the 1000 mg/kg bw/day group. In the absence of significant effects on WBC and lymphocytes, thymus findings are probably of little biological relevance. Historical control incidence is not available for comparison. - Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Males: No dose-related effects were observed.
Females - Sacrificed at Day 4 of lactation: 2 cases of involution of thymus were seen in the 100 mg/kg bw/day group and 5 cases in the 1000 mg/kg bw/day group. A case of pale coloured area in kidney was seen in the 100 mg/kg bw/day and the 1000 mg/kg bw/day groups respectively. A case of pale coloured renal cortex was observed in another animal of the 1000 mg/kg bw/day group. - Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Males - 1 day after termination of administration period:
Thymus: Two cases of hemorrhage were seen in the 1000 mg/kg bw/day group, one case in the control group. In the absence of a dose-response relationship, this is considered incidental.
Heart: Small areas of myocardial degeneration were seen in 2 cases in the control group. No other abnormalities were observed.
Liver: No treatment-related findings were observed. Ten cases of very slight microgranuloma were seen respectively in the control and the 1000 mg/kg bw/day groups. Slight fatty changes in peripheral zone were seen in a case of the control group and in four cases of the 1000 mg/kg bw/day group. Therefore, there was no significant difference in severity and incidence of the findings between the control and the 1000 mg/kg bw/day groups. A case of very slight focal necrosis was seen in the 1000 mg/kg bw/day group.
Kidney: Large numbers of regenerating tubular epithelium were observed in three cases in the 300 mg/kg bw/day group and twelve cases in the 1000 mg/kg bw/day group compared to the control groups. The severity was augmented in the 1000 mg/kg bw/day group. The regenerating epithelial cells were found predominantly in convoluted proximal tubules, showing increased cell density, slightly enlarged nucleoli, and slightly bright or basophilic cytoplasm. In most cases, slightly-yellowish debris was noted in the tubular lumen. A single case of cast in tubular lumen was found in the 100 mg/kg bw/day group. In all groups, including the control group, eosinophilic bodies were observed with no significant differences in incidence and severity among the groups.
Adrenal cortex : Brown pigment deposits were observed both in the 1000 mg/kg bw/day and the control groups but there is no significant difference in incidence and severity.
Spleen: Brown pigment deposits and extramedullary hematopoiesis were found both in the 1000 mg/kg bw/day and the control groups, with no significant difference in incidence and severity.
Testis: Atrophy of tubule was found in 2 cases in the control group and 3 cases in the 1000 mg/kg bw/day group. One of the cases in the 1000 mg/kg bw/day group had calcification in the tubule.
Epididymis: Decreased numbers of sperm were noted in each one case in the control and the 1000 mg/kg bw/day groups. Both animals had atrophy of the tubule.
Females
Thymus: A case of very slight and a case of slight involution were found in the control group. In the 1000 mg/kg bw/day group, increased numbers of involution were found with a case rated "very slight", 3 cases rated "slight", and 2 cases rated "moderately slight".
Liver: Very slight microgranuloma was seen in a case of the control and 2 cases of the 1000 mg/kg bw/day group sacrificed at Day 4 of lactation, and one non-pregnant animal in the control group sacrificed at Day 25 of pregnancy. Very slight to slight fatty changes in peripheral zone were seen in 3 cases in the control group, and very slight to moderate fatty changes in 2 cases in the 1000 mg/kg bw/day group. There were no significant differences in severity and incidence between the control and the 1000 mg/kg bw/day groups.
Kidney: In all treatment groups sacrificed at Day 4 of lactation, increased numbers of incidences of regenerating tubular epithelium were observed. The findings are accompanied with foamy epithelial cells and vacuolar degeneration predominantly in convoluted proximal tubule. In many cases, necrotized epithelial cells were noted, and eosinophilic necrotized cells and yellowish debris were contained in the tubular lumen. In tubular basement of these animals, regenerating epithelial cells included large-sized basophilic cytoplasma. The incidence was similar in all dose groups; the severity of this lesion was slightly increased in the high-dose group.
In all dose groups, there were some animals completely free of kidney findings. Among those were a non-delivering animal (total implantation loss) in the 100 mg/kg bw/day group, 2 non-pregmant animals in the 300 mg/kg bw/day group, and a non-copulated animal in the 1000 mg/kg bw/day group.
Other kidney findings that are considered incidental included each one case of cast in the tubular lumen in the control and the 1000 mg/kg bw/day groups, each one case of slight vacuolar degeneration in the control and the 100 mg/kg bw/day groups, and each one case of focal dilatation of tubule in the 100 mg/kg bw/day and the 1000 mg/kg bw/day groups. The case of cast of the animal in the control group was considered be associated with the very slight incidence of chronic nephropathy.
Adrenal cortex: A case of very slight brown pigment deposit and a case of focal necrosis were observed in the 1000 mg/kg bw/day group.
Spleen: Brown pigment deposits and extramedullary hematopoiesis were observed in 11 animals in the control group and 12 animals in the 1000 mg/kg bw/day group. Two cases were also found in non-pregnant animals in the control group, sacrificed at Day 25 of pregnancy. There were no clear differences in incidence and severity between the treated and the control groups.
Ovary: No abnomarities were found with non-pregnant animals (two in the control and two in the 300 mg/kg bw/day groups) and in the non-copulated animal ( one in the 1000 mg/kg bw/day group). - Histopathological findings: neoplastic:
- no effects observed
Effect levels
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Sex:
- male
- Basis for effect level:
- histopathology: non-neoplastic
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- < 100 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- histopathology: non-neoplastic
Target system / organ toxicity
- Key result
- Critical effects observed:
- yes
- Lowest effective dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- System:
- urinary
- Organ:
- kidney
- Treatment related:
- yes
Applicant's summary and conclusion
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.