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

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)

Data source

Reference

Reference Type:

publication

Title:

LONG-TERM TOXICITY OF SUNSET YELLOW FCF IN MICE

Author:

I. F. GAUNT and P. L. MASON P. GRASSO and IDA S. Kiss

Year:

1974

Bibliographic source:

Food and Cosmetic toxicology, Vol. 12, pp. 1-10, 1974.

Materials and methods

Principles of method if other than guideline:

80 weeks chronic repeated dose oral toxicity study of Sunset Yellow examination in Mice of the Charles River CD strain to evaluate adverse effects and their reversibility and the non observed- effect level.

GLP compliance:

not specified

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 6-hydroxy-5-[(4-sulfonatophenyl)diazenyl]naphthalene-2-sulfonate

Details on test material:

- Name of test material: Sunset Yellow FCF
- Molecular formula: C16H12N2O7S2.2Na
- Molecular weight: 454.38
- Substance type: organic
- Physical state: solid

Test animals

Species:

mouse

Strain:

other: Charles River CD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SPF breeding colony
- Weight at study initiation: Male- 21-30 g and female - 17-25 g
- Fasting period before study: no
- Housing: housed in cages of 15
- Diet (e.g. ad libitum): ground Oxoid pasteurized breeding diet; ad libitum
- Water (e.g. ad libitum): ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21± 1°C
- Humidity (%):50-60%

Administration / exposure

Route of administration:

oral: feed

Vehicle:

other: basic diet

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: Basic diets containing 2000, 4000,8000,16000 mg/l (0.2, 0.4, 0-8 or 1.6%) Sunset Yellow FCF
DIET PREPARATION
- Rate of preparation of diet (frequency): Daily
- Mixing appropriate amounts with (Type of food): ground Oxoid pasteurized breeding diet

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

80 weeks

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
2000,4000,8000,16000 mg/kg (0.2, 0.4, 0.8 or 1.6% respectively)
Basis:
nominal in diet

No. of animals per sex per dose:

Control group:60 male and 60 females
Test group: 30 male and 30 females

Control animals:

yes, concurrent vehicle

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Cage side observations: avoid further fighting all the mice were caged individually from month 8. Any mouse showing signs of ill health was isolated, to be returned to its cage.
BODY WEIGHT: Yes - Time schedule for examinations:
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
- Animals fasted: No data
- How many animals: ten male and ten female mice
- Parameters checked: hemoglobin concentration, packed cell volume and counts, Differential leucocyte counts and reticulocyte counts.
ORGAN WEIGHT: Yes
-Brain, heart, liver, kidneys, spleen, stomach, small intestine, caecum and testes were weighed

Sacrifice and pathology:

SACRIFICE : Mice killed by exsanguination from the aorta under barbiturate anaesthesia.
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
All tissues from the control mice and those fed 1.6% Sunset Yellow FCF were examined microscopically, while at the lower dietary levels examination was confined to the liver and kidney together with any tissue seen to be abnormal at autopsy.

Other examinations:

Behavior and were weighed at 4-wk intervals throughout the study.
During the first half of the study it was noticed that there was a tendency for the male mice to fight. Bite lesions of the anogenital region were particularly frequent and these were associated with obstructions of the urinary tract. To avoid further fighting, all the mice were caged individually from month 8.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Description (incidence and severity):

No changes in body-weight gains.

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):

No evidence of any haematological 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):

No significant differences between the organ weights or relative organ weights of the test groups and the corresponding controls.

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

NON-NEOPLASTIC- No differences between treated and control mice in the incidence or severity of the lesions seen.

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

16 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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 (Table 1). Many of the male mice dying or killed during the first half of the study were those that had been fighting.

Applicant's summary and conclusion

Conclusions:

The 80 weeks chronic repeated dose study on male and female Charles River CD mouse indicated that no effects observed on body weight, organ weight, haematology and histopathology.
Thus, on the basis of study results the NOAEL (no observed adverse effect level) was observed to be 16000 mg/kg diet.

Executive summary:

In order to determined the repeated oral toxicity ofSunset Yellow FCF, a 80weeks repeated dose toxicity study in Charles River CD mouse (male and female) was conducted at dose levels of 2000,4000,8000,16000 mg/kg (0.2, 0.4, 0.8 or 1.6% respectively) by oral diet route .

From experimental study effects observed as No changes in body-weight gains, no significant differences between the organ weights, no evidence of any adverse effect to hematological examinations, no differences between treated and control mice in the incidence or severity of the lesions seen at high dose level.

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. Many of the male mice dying or killed during the first half of the study were those that had been fighting.

Thus, on the basis of above results the NOAEL (no observed adverse effect level) forSunset Yellow FCFwas considered to be 16000 mg/kg diet.