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

Endpoint summary

Description of key information

The substance disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate does not exhibit repeated dose toxicity by the oral,inhalation and dermal route.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

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

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%

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

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

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.

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

Dose descriptor:

NOAEL

Effect level:

16 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: see 'Remark'

Critical effects observed:

not specified

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

16 000 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

The data is K2 level as the data has been obtained from the experimental study from the reliable journal 'Food and Cosmetic toxicology'.

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

repeated dose toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

other:

Critical effects observed:

not specified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records

Reference

Endpoint:

sub-chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Principles of method if other than guideline:

The repeated dose toxicity study was conducted to evaluate the toxic effects of administration of Acid Orange 7 to rabbits by the dermal route for 90 days.

GLP compliance:

not specified

Species:

rabbit

Strain:

not specified

Sex:

not specified

Type of coverage:

open

Vehicle:

other: water as well as USP White Ointment

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

For abraded skin for 21 days
For intact skin for 90 days.

Frequency of treatment:

Daily

Remarks:

Doses / Concentrations:
0,0.1 and 1.0% (Equivalent to 1000 and 10000 mg/kg)
Basis:

No. of animals per sex per dose:

0 mg/l = 3 animals
1000 mg/l =3 animals
10000 mg/l =3 animals

Control animals:

yes, concurrent vehicle

Observations and examinations performed and frequency:

DETAILED CLINICAL OBSERVATIONS: Yes
HAEMATOLOGY: Yes
URINALYSIS: Yes

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Clinical signs:

no effects observed

Description (incidence and severity):

no mortality was observed.

Dermal irritation:

not specified

Mortality:

no mortality observed

Description (incidence):

no mortality was observed.

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:

no effects observed

Description (incidence and severity):

Haematological values was normal

Clinical biochemistry findings:

not specified

Urinalysis findings:

no effects observed

Description (incidence and severity):

urinary components were normal

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Description (incidence and severity):

Gross autopsies disclosed no dose-related findings.

Histopathological findings: non-neoplastic:

no effects observed

Description (incidence and severity):

no effects observed

Histopathological findings: neoplastic:

not specified

Dose descriptor:

NOAEL

Effect level:

10 000 other: mg/kg

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: Effects: There was no mortality or any evidence of systemic toxicity. Haematological values, growth responses and urinary components were normal. Gross autopsies disclosed no dose-related findings.

Critical effects observed:

not specified

Conclusions:

The 90 days subchronic repeated dose dermal study on rabbit indicated that no effects observed on mortality, urinalysis, haematology and histopathology.
Thus, on the basis of study results the NOAEL (no observed adverse effect level) was observed to be 10000 mg/kg.

Executive summary:

In order to determined the repeated dermal toxicity of Acid Orange 7, a 90 days repeated dose toxicity study in rabbits was conducted at dose levels of 0(control),0.1 and 1.0% (Equivalent to 1000 and 10000 mg/kg) by dermal route .

From experimental study there was no mortality or any evidence of systemic toxicity. Hematological values, growth responses and urinary components were normal. Gross autopsies disclosed no dose-related findings.

Thus, on the basis of above results the NOAEL (no observed adverse effect level) for Acid Orange 7 considered to be 10000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

10 000 mg/kg bw/day

Study duration:

subchronic

Species:

rabbit

Quality of whole database:

The data is K4 level as the data has been obtained from the experimental study from the study report of 'Toilet Goods Association'

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Repeated dose toxicity oral:

Based on the various studies available with Klimish rating 2 and 4 for the target substance CAS: 2783-94-0.

The results for target are summarized as follows

Sr. No	End point	Value	Species/strain	Route	Effects	Remarks
1.	NOAEL	16000 mg/kg diet	Mouse (Charles River CD)	oral: feed	No changes in body-weight gains,no significant differences between the organ weights,no evidence of any adverse effect to haematological examinations,no differences between treated and control mice in the incidence or severity of the lesions seen.	Data from publication’Food and Cosmetic toxicology’ for target CAS: 2783-94-0.
2.	LOAEL	15000 mg/kg diet	Rat	oral: feed	Lowered white cell count,Decrease in liver weight and weight of the spleen in two of the groups,reduced food consumption.	Data from study report ‘Department of National Health and Welfare’ for target CAS: 2783-94-0.
3.	NOAEL(female rat)	6000 mg/kg diet	Rat (Fischer 344)	oral: feed	No mortality was observed.	Data from study report of ‘NTP’for target CAS: 2783-94-0.
	NOAEL(male rat)	12000 mg/kg diet			No deaths were observed.
	LOAEL(female rat)	12500 mg/kg diet			decreases in mean body weight gain
	LOAEL(male rat)	25000 mg/kg diet			Decreases in mean body weight gain
4.	NOAEL	<6000 and 50000 mg/kg diet	Mouse (B6C3F1)	oral: feed	No gross or microscopic lesions were observed.
5.	LOAEL	100000 mg/kg diet	Mouse (B6C3F1)	oral: feed	Mean body weight gain among was depressed.	Data from study report of ‘NTP’for target CAS: 2783-94-0.

 

Based on the studies summarized in the above table with oral routes it can be observed that the endpoint lowest observed adversed effect (LOAEL) value varies between 12500 mg/kg diet to 100000 mg/kg diet mg/kg diet and no observed adversed effect level (NOAEL) value varies between 6000 mg/kg diet to 50000 mg/kg diet based on the data from publication and study report for target substance. The effect observed on the above doses are-

*Lowered white cell count, Decrease in liver weight and weight of the spleen in two of the groups, reduced food consumption.

*Decreases in mean body weight gain.

*Mean body weight gain among was depressed.

During experiment no effects observed for following parameters-

* 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.

*No mortality was observed. 

 Based on the above results it can be concluded that the lowest observed adversed effect (LOAEL) is 12500 mg/kg diet , thus based on this value it can be concluded that substance CAS: 2783-94-0 (Sunset Yellow FCF) is considered to be not toxic to repeated dose via oral route below the dose level of 12500 mg/kg diet.

Repeated dose toxicity (Inhalation)

For disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate, repeated dose toxicity testing by the inhalation route was considered for waiver given that the substance has low vapour pressure of 0.000000000133Pa at 25 degC as well as the particle size distribution indicates that the majority particle size is 250 (61.1%)micro meter. Thus, exposure by inhalation route is also unlikely for disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate given the comparatively larger size of the particulates.

Repeated dose toxicity (Dermal)

Based on the studies available with Klimish rating 4 for the read across substances of target CAS: 2783-94-0.

The results for read across substances are summarized as follows

Sr. No	End point	Value	Species/strain	Route	Effects	Remarks
1.	NOAEL	10000 mg/kg	Rabbit	Dermal	There was no mortality or any evidence of systemic toxicity. Haematological values, growth responses and urinary components were normal. Gross autopsies disclosed no dose-related findings.	Experimental data from study report of”Toilet Goods Association”for read across CAS:633-69-5
2.	NOAEL	50000 mg/kg	Mouse	Dermal	No dye-related anomalies were noted in terms of survival, or gross and histopathology of major organs and the skin.	Experimental data from study report of”5Hazelton Laboratories”for read across CAS:25956-17-6

 

Based on the studies summarized in the above table with dermal routes it can be observed that the endpoint no observed adversed effect level (NOAEL) value varies between 10000 mg/kg to 50000 mg/kg based on the data from study report for read across substance. No effects was observed on the above doses as-

* There was no mortality or any evidence of systemic toxicity. Haematological values, growth responses and urinary components were normal. Gross autopsies disclosed no dose-related findings.

* No dye-related anomalies were noted in terms of survival, or gross and histopathology of major organs and the skin.

In the absence of repeated dose toxicity by dermal route data for Sunset Yellow FCF, data from two read-across chemicals have been used. Since it is expected to show the similar toxicological effect based on the effects observed on the other category members. Thus from above results the no observed adversed effect (NOAEL) is 10000 mg/kg concluded that substance CAS: 2783-94-0 (Sunset Yellow FCF) is considered to be not toxic to repeated dose via dermal route below the dose level of 10000 mg/kg.  

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:

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.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:

For disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate, repeated dose toxicity testing by the inhalation route was considered for waiver given that the substance has low vapour pressure of 0.000000000133Pa at 25 degC as well as the particle size distribution indicates that the majority particle size is 250 (61.1%)micro meter. Thus, exposure by inhalation route is also unlikely for disodium 6-hydroxy-5-[(4-sulphonatophenyl)azo]naphthalene-2-sulphonate given the comparatively larger size of the particulates.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:

The 90 days subchronic repeated dose dermal study on rabbit indicated that no effects observed on mortality, urinalysis, haematology and histopathology.

Thus, on the basis of study results the NOAEL (no observed adverse effect level) was observed to be 10000 mg/l.

Justification for classification or non-classification

The substance do not show repeated dose toxicity effect for oral,inhalation and dermal route and thus will not be considered for further classification