Disodium 3-[(2,4-dimethyl-5-sulphonatophenyl)azo]-4-hydroxynaphthalene-1-sulphonate

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: Repeated dermale toxicity study

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

SKIN PAINTING STUDIES IN MICE ON 11 FD&C AND D&C COLORS: F D ~ GCre en NO. 3, Red No. 2, Red No. 4, Yellow No. 6, and External D8.C No. 7, D8.C Orange No. 4, Violet No. 2, Red No. 17, Red No. 34, and Yellow No. 7

Author:

STEVEN CARSON

Year:

1984

Bibliographic source:

J. Toxicol.-Cut. & Ocular Toxicol. 3(3), 309-331 (1984)

Materials and methods

Principles of method if other than guideline:

Repeated dermale toxicity study of FD&C Red 4 in mice

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

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

Constituent 2

Reference substance name:

FD&C Red 4

IUPAC Name:

FD&C Red 4

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):C18-H14-N2-O7-S2.2Na C18-H16-N2-O7-S2.2Na- 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

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

Doses / concentrations

Remarks:

Doses / Concentrations:1.0 % (1500 mg/kg bw/day)Basis:nominal conc.

No. of animals per sex per dose:

Total: 3000 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

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Histopathological findings: non-neoplastic:

no effects observed

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 consumptionBody 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 availableReproductive function: sperm measures: No data availableReproductive performance: No data availableOrgan weights: No data availableGross 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 findingsNo 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

Results: F1 generation

General toxicity (F1)

Clinical signs:

not specified

Mortality / viability:

not specified

Body weight and weight changes:

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

Overall reproductive toxicity

Reproductive effects observed:

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	%S^a	SI^b	%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-Webstermale and female mice were treated withFD &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 effect were observed on survival, clinical sign and body weight of treated male and femlae mice as compared to control. Similarly, lesion in Mammary Gland and Subcutaneous papillary were obseved gross pathologically in treated mice, but the obsrved effect were 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-Webstermale and female mice were treated with FD&C Red 4.