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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Repeated dermal toxicity study
Type of information:
experimental study
Adequacy of study:
weight of evidence
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:
other: Repeated dose toxicity study
Principles of method if other than guideline:
Reproductive toxicity study of test material was performed in mice by repeated dermal application for 18 months.
GLP compliance:
not specified
Limit test:
no
Justification for study design:
No data available

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sudan III
- Molecular formula: C22H16N4O
- Molecular weight : 352.3954 g/mol
- Substance type:Organic
- Physical state:Solid
-Smiles : c12c(\N=N\c3ccc(\N=N\c4ccccc4)cc3)c(ccc1cccc2)O
- InChI: 1S/C22H16N4O/c27-21-15-10-16-6-4-5-9-20(16)22(21)26-25-19-13-11-18(12-14-19)24-23-17-7-2-1-3-8-17/h1-15,27H/b24-23+,26-25+
Specific details on test material used for the study:
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 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: 0.1 % solution of sodium lauryl sulfate
Details on exposure:
PREPARATION OF DOSING SOLUTIONS:
The test material diluted in 0.1 % solution of sodium lauryl sulfate
DIET PREPARATION
- Rate of preparation of diet (frequency):No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food:No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): The test material dissolved in 0.1 % solution of sodium lauryl sulfate
- Concentration in vehicle: 1.0 % (1500 mg/kg bw/day)
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity:No data available
Details on mating procedure:
No data available
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data available
Duration of treatment / exposure:
18 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:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule:
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations:Mean body weight was determined at 3,6, 9, 12, 15, and 18 months;

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes / No / No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data
- Time schedule for examinations:

OTHER:Survival ,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):
SACRIFICE: yes after 18 months
- Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]
- Maternal animals: All surviving animals [describe when, e.g. after the last litter of each generation was weaned.]

GROSS NECROPSY: yes
Organs were fixed in 10% formalin solution after recording any gross pathological findings


HISTOPATHOLOGY / ORGAN WEIGHTS: yes
The tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.
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
Description (incidence and severity):
No abnormalities were observed in treated mice as compared to control.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No effect on survival of treated mice were obserevd as compared to control.
Body weight and weight changes:
no effects observed
Description (incidence and severity):
No significant effect was observed on body weight of treated mice as compared to control.
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
No significant effect was observed on food consumption of treated mice as compared to control.
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
Description (incidence and severity):
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 miceNo significant difference in the incidence of this lesion were observed as compared to control and considered to be not treatment related.
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
Remarks on result:
other: No effects was observed on reproductive organ

Target system / organ toxicity (P0)

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

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 examined
Food consumption and compound intake (if feeding study):
not examined
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: not specified
Generation:
F1
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: not specified
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

Applicant's summary and conclusion

Conclusions:
In reproductive toxicity study, No effects was observed on reproductive organ, the NOAEL was considered to be 1500 mg/kg bw/day. When Swiss-Webster male and female mice were treated with test material by repeated application for 18 months.
Executive summary:

The reproductive toxicity study was considered on the bases of a repeated dose dermal toxicity study, Swiss-Webster male and female mice were treated with test material in the concentration of 1500 mg/kg bw/day in 0.1 % solution of sodium lauryl sulfate applied twice weekly on 6 cm2dorsal area of skin for 18 months. No effect was 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. No effects were observed on male and female reproductive organ. Therefore, NOAEL was considered to be 1500 mg/kg bw/day when Swiss-Webster male and female mice were treated with test material by dermal application.