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EC number: 235-428-9 | CAS number: 12225-21-7 This substance is identified in the Colour Index by Colour Index Constitution Number, C.I. 19140:1.
- 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:
- chronic toxicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- 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
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- A chronic toxicity/carcinogenicity study of FD&C Yellow No. 5 (Tartazine) in mice.
- Author:
- Borzelleca J. and Hallagan J.
- Year:
- 1 988
- Bibliographic source:
- Food and Chemical Toxicology.Vol. 26, No. 3, pp. 189-194, 1988
- Reference Type:
- other: Authoritative data base
- Title:
- GCID: 133984
- Author:
- ACToR database
- Year:
- 2 011
- Bibliographic source:
- ACToR (Aggregated Computational Toxicology Resource):- Borzelleca J. and Hallagan J. (1988b) A chronic toxicity/carcinogenicity study of FD & C Yellow No. 5 (Tartazine) in mice. Fd Chem Toxic 26, 189-194.
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: Refer below principle
- Principles of method if other than guideline:
- The chronic study was conducted to evaluate the toxic effects of repeated administration of trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate [FD & C Yellow No. 5 (tartrazine)] to Charles River CD-1 mice by the oral route.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
- EC Number:
- 217-699-5
- EC Name:
- Trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
- Cas Number:
- 1934-21-0
- Molecular formula:
- C16-H12-N4-O9-S2.3Na
- IUPAC Name:
- trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate
- Details on test material:
- - Name of test material (as cited in study report):trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate [FD & C Yellow No. 5 (tartrazine)]
- Molecular formula :C16H12N4O9S2.3Na
- Substance type:organic
- Physical state:Soild
Constituent 1
- Specific details on test material used for the study:
- - Name of test material : trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophenylazo)pyrazole-3-carboxylate [FD & C Yellow No. 5 (tartrazine)]
- Molecular formula: C16H12N4O9S2.3Na
- Moleculat weight: 534.3681 g/mol
- Substance type: organic
- Physical state: Solid
- Purity: 90%
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Details on species / strain selection:
- No data
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, MA
- Age at study initiation: 42 days
- Weight at study initiation: No data
- Fasting period before study: No data
- Housing: The mice were housed individually in stainless-steel cages kept in a separate room phase
- Diet (e.g. ad libitum): Purina Rodent Chow , ad libitum
- Water (e.g. ad libitum): N/A
- Acclimation period: N/A
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 2 0-21°C
- Humidity (%): 40--60%
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12-hr light/dark cycle.
Administration / exposure
- Route of administration:
- oral: feed
- Details on route of administration:
- No data
- Vehicle:
- other: diet as Purina Rodent Chow
- Details on oral exposure:
- Fresh diets were prepared and presented weekly at dose levels of 0, 0, 0.5, 1.5 or 5.0% (Actual Dose levels: Males: 714, 2173 or 8103 mg/kg/d; Females: 870, 2662 or 9735 mg/kg/day). The diets were blended in a twin-shell blender, and assays were performed to determine the homogeneity and stability of FD & C Yellow No. 5 in the prepared diets prior to the start of the study. Dietary concentrations of the compound were determined weekly during the first 13 wk of the study, and then monthly thereafter. Analyses of the basic feed for heavy metals, chlorinated hydrocarbons, and aflatoxin were conducted on all lots of feed used during the study.
DIET PREPARATION
- Rate of preparation of diet (frequency): Weekly
- Mixing appropriate amounts with (Type of food): The basal diet (Purina Rodent Chow)
- Storage temperature of food: The basal diet (Purina Rodent Chow) and the experimental diets were stored in an environmentally-controlled room with limited access. The test compound was stored in sealed containers in a locked closet.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Purina Rodent Chow
- Concentration in vehicle: 0, 0, 0.5, 1.5 or 5.0% (Actual Dose levels:Males: 714, 2173 or 8103 mg/kg/d; Females: 870, 2662 or 9735 mg/kg/day)
- Amount of vehicle (if gavage): No data
- Lot/batch no. (if required): No data
- Purity: No data - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses of the basic feed for heavy metals, chlorinated hydrocarbons and aflatoxin were conducted on all lots of feed used during the study. These analyses demonstrated that the basic feed contained acceptably low levels of contaminants, that the diets were prepared properly, and that the dietary content of the test material was stable.
- Duration of treatment / exposure:
- 104 weeks
- Frequency of treatment:
- Daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 0, 0.5, 1.5 or 5.0% (Actual Dose levels:Males: 714, 2173 or 8103 mg/kg/d; Females: 870, 2662 or 9735 mg/kg/day)
Basis:
no data
- No. of animals per sex per dose:
- Total: 600
0 % (control) - 60 male and 60 female mice
0 % (control) - 60 male and 60 female mice
0.5 % - 60 male and 60 female mice
1.5 % - 60 male and 60 female mice
5.0 % - 60 male and 60 female mice - Control animals:
- yes, concurrent vehicle
- Details on study design:
- No data
- Positive control:
- No data
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily with at least 5 hr between observations.
- Cage side observations checked in table [No.?] were included. Death and mortality
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Twicw weekly for gross signs of toxicity and Detailed physical examinations for signs of toxicity and palpation for masses were conducted weekly.
BODY WEIGHT: Yes
- Time schedule for examinations: weekly for the first 14 wk, bi-weekly for wk 16-26, and monthly thereafter
FOOD 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, weekly for the first 14 wk, bi-weekly for wk 16-26, and monthly thereafter
- 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
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations: No data
OPHTHALMOSCOPIC EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
HAEMATOLOGY: Yes
- Time schedule for collection of blood: at months 3, 6, 12, 18 and 24
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 10 animals/sex from each group
- Parameters checked in table [No.?] were examined. haemoglobin, haematocrit, erythrocyte and total and differential leucocyte counts, and erythrocyte morphology.
CLINICAL 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. No data
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. No data
NEUROBEHAVIOURAL EXAMINATION: No data
- Time schedule for examinations: No data
- Dose groups that were examined: No data
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data
IMMUNOLOGY: No data
- Time schedule for examinations: No data
- How many animals: No data
- Dose groups that were examined: No data
- Parameters checked in table [No.?] were examined. No data
OTHER: No data - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes, Necropsies were conducted on all animals dying spontaneously, killed in a moribund condition, or killed on schedule. Both absolute and relative organ weights were recorded for brain, gonads, kidneys, liver, spleen and thyroid.
HISTOPATHOLOGY: Yes, complete histological study was conducted on all animals from the two control groups and from the high-dose (5.0%) group.The following tissues were examined histologically for all control and high-dose mice: adrenals (two), aorta (abdominal), bone and marrow (femur), blood smear, brain (three sections: through the frontal cortex and basal ganglia, parietal cortex and thalamus, and cerebellum and pons), oesophagus, eye (two, with optic nerve), gall bladder, heart (with coronary vessels), liver, lung and mainstem bronchi (lungs inflated with formalin), lymph nodes (mesenteric and mediastinal), mammary gland (inguinal), nerve (sciatic), ovaries, pancreas, pituitary, prostate, salivary gland (mandibular), seminal vesicles (two), skeletal muscle (biceps femoris), skin, spinal cord (cervical), spleen, stomach, testes (with epididymides), thymus, thyroid with parathyroid, trachea, urinary bladder (inflated with formalin), uterus, any tissue with gross changes of an uncertain nature (with a section of an area of normal appearance from the same tissue), and any
tissue or masses or suspect tumours with regional lymph nodes. - Other examinations:
- No data
- Statistics:
- The variances of the two control groups were statistically tested for equality by using the the F test. If the variances were equal a standard independent two-sample test was used to determine equality of means. If the variances differed, Welch's t test was used to determine the equality of means,using the Smith-Satterthwaite correction for unequal variances.
Statistical evaluation of the equality of means of control and treated groups was made by the one- way analysis of variance (ANOVA) technique.
Bartlett's test was performed to determine whether groups had equal variance and parametric procedures were used if they did not. The one-way ANOVA was applied using the F distribution to assess significance.
Dunnett's test was used to determine which means were significantly different from the controls.If a non-parametric procedure for testing equality of means was indicated, the Kruskal-Wallis test was used. If differences from the controls were indicated,a summed rank test was used to determine which groups differed significantly.A statistical test for trend among the dose levels was also performed. In the parametric case standard regression techniques were used with a test for trend and lack of fit.In the non-parametric case,Jonckheer's test for monotonic trend was used.
The statistical analysis of tumour incidence data was performed using contingency table techniques.For each comparison, a 2 × 2 table was constructed from the numbers of animals with and without the event of interest in both the control and treated groups.The table was evaluated by the Fisher exact test.
The data on time to neoplastic lesion, and survival data were analyzed for each sex separately by the series of programs included in the National Cancer Institute package for histopathologically proven tumours,time to tumour, and time to death.Total benign neoplastic lesions, total malignant neoplastic lesions and animals bearing benign and/or malignant neoplastic lesions were also analyzed.
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Physical observations noted throughout the study included hair loss (due to friction against the cage), lacrimation, nasal discharge, staining of hair in the anogenital region and soft stools. These observations occurred randomly and in low incidence throughout all groups and were not related to compound administration. Amber or yellow-brown coloured urine was noted at all treatment levels within 1 wk of the start of the study. The faeces of mice fed at dietary levels of 1.5 and 5.0% were purple and yellow-brown, respectively. Yellow hair and skin were noted in all treatment groups.
- Mortality:
- no mortality observed
- Description (incidence):
- The survival of the mice was found to be similar for the treated and control groups throughout the study.
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean body weights of male and female mice in the 5.0% treatment group, and male mice in the 1.5% treatment group were lower than the controls at a number of sampling intervals. These differences, while usually slight, were statistically significant at several intervals. This decrease is not considered toxicologically significant and may be due to the non-nutritive character of FD & C Yellow No. 5.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Mean food consumption was increased in male mice that consumed 5.0% FD & C Yellow No. 5. The differences from control values were slight but statistically significant at several sampling intervals. The mean food consumptions among other treatment groups and controls were similar
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- No consistent statistically significant differences between control and treated animals were observed for the haematological parameters evaluated
- 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:
- no effects observed
- Neuropathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- A variety of common neoplastic, inflammatory and degenerative lesions were observed macroscopically and histologically. These lesions occurred in similar
incidence among control and treated mice and were not considered related to treatment with the compound. There was no significant difference among groups in the number of tumour-bearing animals - Other effects:
- not specified
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 8 103 other: mg/kg/day
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No consistent, significant compound-related adverse effects were noted on clinical signs and mortality,body weight and weight gain,food consumption and compound intake,haematology, urinalysis, gross pathology and histopathology: neoplastic.
- Dose descriptor:
- NOAEL
- Effect level:
- 9 735 other: mg/kg/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No consistent, significant compound-related adverse effects were noted on clinical signs and mortality,body weight and weight gain,food consumption and compound intake,haematology, urinalysis, gross pathology and histopathology: neoplastic.
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Table 1. Survival and group mean body weights and percentage difference from control values at study termination for mice fed FD & C Yellow No. 5 in the diet
Dose level (%) |
Survival |
Group body weight (g) |
Difference from control |
Males |
|||
0 |
30/60 |
39 |
+1.3 |
0 |
28/60 |
38 |
-1.3 |
0.5 |
31/60 |
39 |
0 |
1.5 |
21/60 |
38 |
-2.6 |
5.0 |
29/60 |
37 |
-5.1 |
Females |
|||
0 |
20/60 |
33 |
0 |
0 |
34/60 |
33 |
0 |
0.5 |
18/60 |
32 |
-3.0 |
1.5 |
24/60 |
32 |
-3.0 |
5.0 |
33/60 |
30 |
-9.1 |
Table 2. Mean food and compound consumption for mice fed FD &C Yellow No. 5 in the diet.
Dose level (%) |
Food consumption (mg/mouse/day) |
Compound comsumption (mg/kg/day) |
||
Male |
Female |
Male |
Female |
|
0 |
5100 |
5000 |
- |
- |
0 |
5000 |
4900 |
- |
- |
0.5 |
5000 |
4800 |
714 |
870 |
1.5 |
5000 |
5000 |
2173 |
2662 |
5.0 |
5500 |
5200 |
8103 |
9735 |
Table 3. Summary of neoplasms in male and female rats fed FD & C Yellow No. 5 in the diet
Observation |
Dose level (%) |
No. (%) of rats affected |
||||
0 |
0 |
0.5 |
1.5 |
5.0 |
||
Males |
||||||
Total no. of rats examined |
60 |
60 |
27* |
33* |
60 |
|
No neoplasms |
30 (50) |
32 (53) |
- |
- |
34 (56) |
|
Benign neoplasms+ |
20 (33) |
23 (38) |
21 (77) |
13 (39) |
22 (36) |
|
Malignant neoplasms+ |
11 (18) |
16 (26) |
6 (22) |
22 (66) |
20 (33) |
|
Females |
||||||
Total no. of rats examined |
60 |
60 |
28* |
30* |
60 |
|
No neoplasms |
39 (65) |
35 (58) |
- |
- |
28 (46) |
|
Benign neoplasms+ |
38 (46) |
24 (40) |
14 (50) |
10 (33) |
15 (25) |
|
Malignant neoplasms+ |
16 (26) |
18 (30) |
15 (53) |
20 (66) |
15 (25) |
*Only grossly detected masses and lesion were examined from animals in the 0.5 and 1.5% groups.
+ Some rats had benign and malignant neoplasms.
Applicant's summary and conclusion
- Conclusions:
- The no-observed-adverse-effect level established was 5.0% providing an average intake of 8103 and 9735 mg/kg/day for males and females mice, respectively. Lifetime exposure of mice to FD & C Yellow No. 5 (tartrazine) as a dietary admixture at levels up to 5.0% did not demonstrate carcinogenic or toxic effects.
- Executive summary:
Chronic toxicity study was conducted to evaluate the toxic effects of repeated administration of trisodium 5-hydroxy-1-(4-sulphophenyl)-4-(4-sulphophe nylazo)pyrazole-3-carboxylate [FD & C Yellow No. 5 (tartrazine)] to Charles River CD-1 mice by the oral route.Charles River CD-1 mice were fed FD & C Yellow No. 5 in the diet at levels of 0.0, 0.0, 0.5,1.5 or 5.0% (Actual Dose levels:Males: 714, 2173 or 8103 mg/kg/d; Females: 870, 2662 or 9735 mg/kg/day) in a long-term toxicity study for a maximum of 104 weeks. Each group consisted of 60 males and 60 females. The animals were observed for death, mortality, clinical signs of toxicity, hemotology, body weight and food consumption and were subjected to groos and histopathology. No consistent, significant compound-related adverse effects were noted. Physical observations noted throughout the study included hair loss (due to friction against the cage), lacrimation, nasal discharge, staining of hair in the anogenital region and soft stools. These observations occurred randomly and in low incidence throughout all groups and were not related to compound administration. Amber or yellow-brown coloured urine was noted at all treatment levels within 1 wk of the start of the study. The faeces of mice fed at dietary levels of 1.5 and 5.0% were purple and yellow-brown, respectively. Yellow hair and skin were noted in all treatment groups. The survival of the mice was found to be similar for the treated and control groups throughout the study. Mean body weights of male and female mice in the 5.0% treatment group, and male mice in the 1.5% treatment group were lower than the controls at a number of sampling intervals. These differences, while usually slight, were statistically significant at several intervals. This decrease is not considered toxicologically significant and may be due to the non-nutritive character of FD & C Yellow No. 5. Mean food consumption was increased in male mice that consumed 5.0% FD & C Yellow No. 5. The differences from control values were slight but statistically significant at several sampling intervals. The mean food consumptions among other treatment groups and controls were similar. No consistent statistically significant differences between control and treated animals were observed for the haematological parameters evaluated. A variety of common neoplastic, inflammatory and degenerative lesions were observed macroscopically and histologically. These lesions occurred in similar incidence among control and treated mice and were not considered related to treatment with the compound. There was no significant difference among groups in the number of tumour-bearing animals. Based on these considerations, the no- observed - adverse effect level (NOAEL) established in this study was 5.0% (8103 mg/kg/day and 9735 mg/kg/day for male and female mice, respectively). Lifetime exposure of mice to FD & C Yellow No.5 as a dietary admixture at levels up to 5.0% did not demonstrate carcinogenic or toxic effects.
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