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Diss Factsheets

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Repeated dermal toxicity study
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Justification for type of information:
Data from peer reviewed journal

Data source

Reference
Reference Type:
publication
Title:
Reproductive toxicity study of test material was performed in mice by repeated dermal application for 18 months.
Author:
CARSON et al.
Year:
1984
Bibliographic source:
J. Toxicol.-Cut. & Ocular Toxicol.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
other: As mentioned below
Principles of method if other than guideline:
Repeated dermal toxicity study of FD&C Red 4 in mice
GLP compliance:
not specified
Limit test:
no
Justification for study design:
No data available

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate
EC Number:
224-909-9
EC Name:
Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate
Cas Number:
4548-53-2
Molecular formula:
C18H16N2O7S2.2Na
IUPAC Name:
disodium 3-[(2,4-dimethyl-5-sulfonatophenyl)diazenyl]-4-hydroxynaphthalene-1-sulfonate
Test material form:
not specified
Details on test material:
- Name of test material (as cited in study report): FD&C Red 4
- Molecular formula (if other than submission substance):C18H14N2O7S2.2Na C18H16N2O7S2.2Na
- Molecular weight (if other than submission substance): 480.4276 g/mole
- Substance type: Orgainc
- Physical state: No data available
- Impurities (identity and concentrations): No data available
Specific details on test material used for the study:
- Name of test material (as cited in study report): FD&C Red 4
- Molecular formula (if other than submission substance):C18H14N2O7S2.2Na C18H16N2O7S2.2Na
- Molecular weight (if other than submission substance): 480.4276 g/mole
- Substance type: Orgainc
- Physical state: No data available
- Impurities (identity and concentrations): No data available

Test animals

Species:
mouse
Strain:
Swiss Webster
Details on species / strain selection:
No data available
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data available
- Age at study initiation: (P) : No data available
- Weight at study initiation: (P) : 17 to 25 g
- Fasting period before study: No data available
- Housing: Animals of sex were housed five per cage
- Diet (e.g. ad libitum): Purina Laboratory Chow , ad libitum
- Water (e.g. ad libitum): Fresh water, ad libitum
- Acclimation period: No data available


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available

Administration / exposure

Route of administration:
dermal
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: Distilled water
Details on mating procedure:
No data available
Details on analytical verification of doses or concentrations:
No data available
Duration of treatment / exposure:
19.5 months
Frequency of treatment:
Twice weekly
Details on study schedule:
No data available
Doses / concentrations
Remarks:
Doses / Concentrations:
1.0 % (1500 mg/kg bw/day)
Basis:
nominal conc.
No. of animals per sex per dose:
Total: 300
0 mg/kg/bw/day : 100 males and 100 females
1500 mg/kg bw/day: 50 males and 50 females
Control animals:
yes, concurrent vehicle
Details on study design:
No data available
Positive control:
No data available

Examinations

Parental animals: Observations and examinations:
Survival, Body weight, visible or palable growth and behavior were examined.
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
Gross pathology and histopathology were examined.
Postmortem examinations (offspring):
No data available
Statistics:
No data available
Reproductive indices:
No data available
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
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
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Details on results (P0)

Mortality:
No effect on survival of treated mice were obserevd as compared to control.

Clinical signs:
No abnormalities were observed in treated mice as compared to control.

Body weight and food consumption
Body weight:
No significant effect was observed on body weight of treated mice as compared to control.

Test substance intake: No data available

Reproductive function: estrous cycle: No data available

Reproductive function: sperm measures: No data available

Reproductive performance: No data available

Organ weights: No data available

Gross pathology: Lymphoma of Absominal, Involving Viscera, Adenocarcinoma of Mammary Gland, Subcutaneous papillary adenocarcinoma were observed in treated female mice. The observed effect were similar to control.

Histopathology: All grades Malignant lymphoma and Variation in nuclear morphology in Liver, Infarction, Malignant and Myeloid metaplasia, Leukocytic aggregations in Spleen, all grades Malignant lymphoma , Leukemic and round cell infiltration and Leukocytic aggregation in Kidneys , Malignant lymphoma in Lymph Nodes, Malignant lymphoma, Inflammation, pneumonitis, bronchitis, Necrotic changes in Lungs and all grades Malignant lymphoma in Thymus were observed in male and female treated mice.

No significant difference in the incidence of this lesion were observed as compared to control and considered to be not treatment related.
other findings No data available

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effect on survival, clinical sign, body weight, gross pathology and histopathology of reproductive organ

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: No data available
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
other: No data available
Generation:
F1
Based on:
not specified
Sex:
not specified
Basis for effect level:
other: No data available
Remarks on result:
not measured/tested

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Any other information on results incl. tables

Skin Painting Studies in Mice: Percent Survival and Survival Index

 

 

6

12

18

19.5

Series

Sex

%Sa

SIb

%S

SI

%S

SI

%S

SI

FD&C Red 4

M

66

80

30

64

12

49

12

46

 

F

76

91

26

68

2

48

2

44

A%S denotes percent survival.

bSI, survival index: %ratio of mouse days survived compared to anticipated number of days if all the surviving animals lived to the end of the experiment.

C0.1%sodium lauryl sulfate.

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 1500 mg/kg bw/day when Swiss-Webster male and female mice were treated with FD&C Red 4.
Executive summary:

In a repeated dose dermal toxicity study, Swiss-Webster male and female mice were treated with FD &C Red 4in the concentration of 1500 mg/kg bw/day in distilled water applied twice weekly on 6 cm2 dorsal area of skin. No effects were observed on survival, clinical sign and body weight of treated male and female mice as compared to control. Similarly, lesion in Mammary Gland and Subcutaneous papillary were observed gross pathologically in treated mice, but the observed effect was similar to control. In addition, All grades Malignant lymphoma and Variation in nuclear morphology in Liver, Infarction, Malignant and Myeloid metaplasia, Leukocytic aggregations in Spleen, all grades Malignant lymphoma , Leukemic and round cell infiltration and Leukocytic aggregation in Kidneys , Malignant lymphoma in Lymph Nodes, Malignant lymphoma, Inflammation, pneumonitis, bronchitis and Necrotic changes in Lungs and all grades Malignant lymphoma in Thymus were observed in male and female treated mice. No significant difference in the incidence of this lesion were observed as compared to control and considered to be not treatment related. Therefore, NOAEL was considered to be 1500 mg/kg bw/day when Swiss-Webster male and female mice were treated with FD&C Red 4.