Registration Dossier
Registration Dossier
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: 226-109-5 | CAS number: 5281-04-9
- 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

Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- 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 and carcinogenicity study by the dermal route was performed to determine the dermal toxic nature of the test chemical D & C Red no.7 upon repeated application.
- GLP compliance:
- not specified
- 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-[(1E)-2-(4-methyl-2-sulfonatophenyl)diazen-1-yl]naphthalene-2-carboxylate
- Test material form:
- solid
- Details on test material:
- - Name of test material (as cited in study report): 2-Naphthalenecarboxylic acid, 3-hydroxy-4-[(4-methyl-2-sulfophenyl)azo]-, calcium salt- Molecular formula (if other than submission substance): C18H14N2O6S.Ca- Molecular weight (if other than submission substance): 424.445 g/mole- Smiles notation (if other than submission substance): c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- InChl (if other than submission substance): 1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3, (H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Substance type: Organic - Physical state: Solid - Analytical purity: 87%- Impurities (identity and concentrations): 13%
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): D & C Red no.7- Molecular formula (if other than submission substance): C18H14N2O6S.Ca- Molecular weight (if other than submission substance): 424.445 g/mole- Smiles notation (if other than submission substance): c12c(c(c(C(=O)[O-])cc1cccc2)O)\N=N\c1c(cc(C)cc1)S(=O)(=O)[O-].[Ca+2]- InChl (if other than submission substance): 1S/C18H14N2O6S.Ca/c1-10-6-7-14(15(8-10)27(24,25)26)19-20-16-12-5-3-2-4-11(12)9-13(17(16)21)18(22)23;/h2-9,21H,1H3, (H,22,23)(H,24,25,26);/q;+2/p-2/b20-19+;- Substance type: Organic - Physical state: Solid - Analytical purity: 98%- Impurities (identity and concentrations): 2%
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: Swiss Webster derived- 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): Ad libitum- Water (e.g. ad libitum): 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
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 growthREMOVAL OF TEST SUBSTANCE- Washing (if done): No data available- Time after start of exposure: No data availableTEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.1 ml of the vehicle containing 0 or 128.5 mg test material- Concentration (if solution): 0 or 128.5 mg- Constant volume or concentration used: yes- For solids, paste formed: no data availableVEHICLE- Justification for use and choice of vehicle (if other than water): Distilled water- Amount(s) applied (volume or weight with unit): 0.1 ml- Concentration (if solution): 0.1 ml of the vehicle containing 0 or 128.5 mg test material- Lot/batch no. (if required): No data- Purity: no data availableUSE 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:
- 471 days
- Frequency of treatment:
- Twice weekly
Doses / concentrations
- Remarks:
- 0 or 130.6mg/kg/day
- No. of animals per sex per dose:
- Total: 500130.6 mg: 50 males and 50 females0 mg/Kg bw: 150 males and 50 femalesPositive control: 50 males and 50 females
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Preliminary to establishing the dosages for the skin painting studies, the amounts of lipstick ingested by women was established in a study utilizing female volunteers- Rationale for animal assignment (if not random): No data available- Rationale for selecting satellite groups: No data available- Post-exposure recovery period in satellite groups: No data available- Section schedule rationale (if not random): No data available
- Positive control:
- 3, 4-benzpyrene,, dissolved in acetone
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes - Time schedule: daily- Cage side observations checked in table [No.?] were included. MortalityDETAILED CLINICAL OBSERVATIONS: Yes- Time schedule: Twice weekly for gross toxicityBODY WEIGHT: no data- Time schedule for examinations: no dataFOOD 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 dataFOOD 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 dataWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data- Time schedule for examinations: No dataOPHTHALMOSCOPIC EXAMINATION: No data - Time schedule for examinations:- Dose groups that were examined: No dataHAEMATOLOGY: 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 dataCLINICAL 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 dataOTHER:
- Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Animals that died, those sacrificed moribund, and those surviving the 18-month experimental period were necropsied and the tissues including those of 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 tissues were preserved in 10% formalinHISTOPATHOLOGY: Yes, tissues were sectioned, stained with hematoxylin and eosin, and examined. These included skin and any grossly abnormal organs andtissues of all animals in the color experimental group; skin and any grossly abnormal organs and tissues of approximately 50 vehicle control animals (approximatelyequal number of males and females); complete pathology on five males and five females randomly selected vehicle control animals that survived the 18-month experimentalperiod; and complete pathology on five males and five females randomly selected vehicle control animals that survived the 18-month experimental period; and completepathology of five male and five female animals from the positive control group that included induced skin lesions.
- Other examinations:
- No data available
- Statistics:
- Yes ,Mean was observed
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Dermal irritation:
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Mortality: The percent survival of the treated mice changed with the duration of the treatment. The survival was 97% in 4 months, 92% in 10 months, 69% in 12 months and 41% in 18 months respectively.
- 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:
- not specified
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- Histopathology: The incidence of extramedullary hematopoesis of the spleen (5 male and 9 females: 14%) 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.
- Other effects:
- not specified
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 130.6 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- gross pathology
- histopathology: neoplastic
- mortality
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table: Percent survival of mice
Months | 5 | 10 | 16 | 18 |
D & C Red no 7 | 92 | 88 | 69 | 48 |
Table: Details of microscopic analysis
Animal Number | Experimental Days Observed | Location of Lesion | Microscopic Diagnosis |
3F | 485 | Tissue mass beneath the dorsal skin treatment area (appeared to be attached to the spine) | Rather large cells with vacuolated cytoplasm and pyknotic nuclei postmortem autolysis prevented positive identification |
21F | 568 | Tissue mass in intestine |
Reticulam cell sarcoma |
36F | 568 | Tissue mass in near pituitary | Abscess involving the brain and pituitary |
39F | 569 | Nodule on liver | Reticulam cell sarcoma |
40F | 473 | Tissue mass near tritrigerminal nerve | Mass was relatively compact bone contaningspaceswith hematogenic activity |
55M | 502 |
Tissue mass in near pituitary | Abscess involving pituitary |
75M | 446 |
Nodule on kidney | Focal granulomatous process |
88M | 569 | Tissue mass in liver | Hepatic cell adenoma |
93M | 569 | Tissue mass in liver | Hepatic cell adenoma |
100M | 569 | Nodule in kidney | Hepatic cell adenoma |
Applicant's summary and conclusion
- Conclusions:
- The No Observed Adverse Effect Level (NOAEL) for the test compound D and C Red No. 7 is considered to be 130.6 mg/kg/dayin male and female mice for 18 months
- Executive summary:
Repeated dose toxicity by the dermal route was performed to determine the dermal toxic nature of the test compoundD & C Red no. 7upon 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.
Repeated dermal application of 0.1 ml containing 1 mg of dye applied to the dorsal area of ICR (Swiss Webster derived) white mice twice weekly for 18 months failed to produce any adverse effects and hence the No Observed Adverse Effect Level (NOAEL) for the test compoundD & C Red no. 7 is found to be130.6 mg/kg/day in ICR male and female mouse by 18 months of repeated dermal application.
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.
