Aluminium, 6-hydroxy-5-[(4-sulfophenyl)azo]-2-naphthalenesulfonic acid complex

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:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Justification for type of information:

Data is from publication.

Data source

Reference

Reference Type:

publication

Title:

LONG-TERM TOXICITY OF SUNSET YELLOW FCF IN MICE

Author:

I. F. GAUNT and P. L. Mason—Toxicology and P. GRASSO and IDA S. Kiss

Year:

1974

Bibliographic source:

Fd Cosmet, Toxicol. Vol. 12, pp. I-10

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

To evaluate the toxic potential of Sunset Yellow FCF in Charles River CD mice by Long term toxicity study.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate

EC Number:

220-491-7

EC Name:

Disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate

Cas Number:

2783-94-0

Molecular formula:

C16H12N2O7S2.2Na

IUPAC Name:

disodium (5E)-6-oxo-5-[(4-sulfonatophenyl)hydrazinylidene]naphthalene-2-sulfonate

Test material form:

other: solid

Details on test material:

- Name of test material (as cited in study report):Sunset Yellow FCF
- Molecular formula (if other than submission substance):C16H12N2O7S2.2Na
- Molecular weight (if other than submission substance):452.374
- Substance type:solid
- Physical state:organic
- Impurities (identity and concentrations):15%

Specific details on test material used for the study:

- Name of test material (as cited in study report):sunset yellow
- Molecular formula (if other than submission substance):C16H12N2O7S2.2Na
- Molecular weight (if other than submission substance):452.37 g/mol
- Substance type;Organic
- Physical state:solid

Test animals

Species:

rat

Strain:

other: Charles River CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Not available
- Age at study initiation: Not available
- Weight at study initiation: male mice
- Fasting period before study: Not available
- Housing: housed in cages of 15
- Diet (e.g. ad libitum):Oxoid pasteurized breeding diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/- 1°C
- Humidity (%):50-60%
- Air changes (per hr): Not available
- Photoperiod (hrs dark / hrs light): Not available

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: contained in the diet

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Not applicable
DIET PREPARATION
- Rate of preparation of diet (frequency): Not available
- Mixing appropriate amounts with (Type of food): Not available
- Storage temperature of food: Not available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Not available
- Concentration in vehicle: 0.2, 0.4, 0-8 or 1.6%Sunset Yellow FCF in diet
- Amount of vehicle (if gavage): Not available
- Lot/batch no. (if required): Not available
- Purity: Not available

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

80 week

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

0,250,500,1000 and 2000 mg/kg/day

No. of animals per sex per dose:

Control: 60 male and 60 female mice
250mg/kgbw/day-30 male mice and 30 females
500mg/kgbw/day-30 male mice and 30 females
1000mg/kgbw/day-30 male mice and 30 females
2000mg/kgbw/day-30 male mice and 30 females

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: Not available
- Rationale for animal assignment (if not random): Not available
- Rationale for selecting satellite groups: Not available
- Post-exposure recovery period in satellite groups: Not available
- Section schedule rationale (if not random): Not available
Groups of 30 male mice and 30 females, housed in cages of 15, were fed diets containing 0.2, 0.4, 0-8 or 1.6% Sunset Yellow FCF for 80 wk. To avoid fighting, all the mice were caged individually from month 8. The animals were under continual surveillance for any abnormalities in condition or behavior.

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: at 0 ,13, 33, 49 ,65, 81 week

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- 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 data

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: Not examined
- Time schedule for examinations: Not examined
- Dose groups that were examined: Not examined

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at wk 13, 26 and 52 and from all surviving mice at wk 80.
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 10 male and 10 female mice from the control and two highest dietary levels (0.8 and 1.6%)
- Parameters checked- haemoglobin concentration, erythrocytes count , total leucocytes count, Differential leucocyte counts and reticulocyte counts
CLINICAL CHEMISTRY: Not examined
URINALYSIS: Not examined
NEUROBEHAVIOURAL EXAMINATION: Not examined
- Time schedule for examinations: Not examined
- Dose groups that were examined: Not examined
- Battery of functions tested: sensory activity / grip strength / motor activity / other: Not examined

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
Relative organ weights- Brain, Heart, Liver, Spleen, Kidney, Stomach, Small intestine, Caecum and Testes were observed.
HISTOPATHOLOGY: Yes
Histopathological abnormalities: Lung, Liver, Spleen, , Kidney Bladder, Urethra, and Heart were examined for macroscopic abnormalities

Other examinations:

No other examinations reported.

Statistics:

statistically significant (Student's t test): P > 0.05 was observed

Results and discussion

Results of examinations

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

Many of the male mice dying or killed during the first half of the study were those that had been fighting. Frequently there was extensive wetting of the fur in the anogenital area
and on the ventral surface, together with bite lesions and abscesses of the anogenital region.

Mortality:

mortality observed, non-treatment-related

Description (incidence):

There were deaths in all groups during the study but there was no relationship between the number of deaths at any time and the dietary intake of Sunset Yellow FCF

Body weight and weight changes:

no effects observed

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:

no effects observed

Description (incidence and severity):

The haematological examinations conducted during and at the end of the study produced no evidence of any adverse effect due to the administration of Sunset Yellow FCF

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

There were no significant differences between the organ weights or relative organ in treated group compare to control.

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

There were no differences between treated and control mice in the incidence or severity of the lesions seen. There was an unusually high incidence of pyelonephritis and chronic inflammation of the bladder and urethra, but these lesions occurred mainly in the male mice killed because of urinary retention in the early stages of the study.

Histopathological findings: neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

lymphomas and reticulum-cell neoplasms occurred in treated and control mice. Splenic haemangiosarcoma and a mammary carcinoma were found in the female mice fed on the diet containing the lowest level of Sunset Yellow FCF (0.2%). A single tumour of the Harderian gland was found in a female from the group given the 1.6% level. The commonest benign tumours were pulmonary adenomas and benign cysts in the ovary, found with a similar frequency in treated and control mice. The only other tumour occurring in treated mice without a similar finding in the controls was a granulosa-cell tumour of the ovary in a mouse given 1.6%Sunset Yellow FCF.

Details on results:

Clinical signs and mortality:
Deaths occured in all groups during the study but there was no relationship between the number of deaths at any time and the dietary intake of Sunset Yellow FCF.
Histopathology:

Tumors:

Effect levels

Dose descriptor:

NOAEL

Effect level:

2 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No carcinogenic or toxic effect reported at this dose

Remarks on result:

other: No toxic effect were observed.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

Sunset Yellow FCF(2783-94-0) was fed in diet at the dose of 0,250,500,1000 and 2000 mg/kg/day for 80 weeks followed by various examinations. No carcinogenic or toxic effect was observed. No adverse effects were observed in any of the parameters examined upto 2000 mg/kg/day.Hence 2000 mg/kg/day was assessed to be the NOAEL value.

Executive summary:

In this study male and female mice were given diets containing 0,250,500,1000 and 2000 mg/kg/day of Sunset Yellow FCF for 80 wk. The feeding of Sunset Yellow FCF did not adversely affect the death rate within the groups, the rate of body-weight gain, the organ weights or the haematological findings. The incidence and severity of the histopathological findings were similar in treated and control mice and there was no evidence of an increased incidence of tumours in the mice given Sunset Yellow FCF. It is concluded that in mice Sunset Yellow FCF fed at levels of up to 2000 mg/kg/day in the diet is not carcinogenic and does not exert any long-term toxic effects. Hence 2000 mg/kg/day) is assessed to be the NOAEL(No observed adverse effect ) value.