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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data from secondary source

Data source

Reference
Reference Type:
secondary source
Title:
Scientific Committee on Consumer Products, Opinion on:test material
Author:
European Commission (EC) - Scientific Committee on Consumer Products (SCCP)
Year:
2008
Bibliographic source:
Scientific Committee on Consumer Products (SCCP),2008

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
Teratogenic toxicity study of test material was performed on rats.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Hydrogen 3,6-bis(diethylamino)-9-(2,4-disulphonatophenyl)xanthylium, sodium salt
EC Number:
222-529-8
EC Name:
Hydrogen 3,6-bis(diethylamino)-9-(2,4-disulphonatophenyl)xanthylium, sodium salt
Cas Number:
3520-42-1
Molecular formula:
C27H30N2O7S2.Na
IUPAC Name:
sodium 4-[3,6-bis(diethylamino)-2,7-dimethylxanthenium-9-yl]benzene-1,3-disulfonate; 2-(3-diethylamino-6-diethylazaniumylidene-xanthen-9-yl)-5-sulfo-benzenesulfonate
Details on test material:
- Name of test material (as cited in study report):Acid Red 52
- Molecular formula : C27H30N2O7S2.Na
- Molecular weight : 580.6551 g/mol
- Substance type:Organic
Physical State: Solid

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
No data available

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: bi-distilled water containing 1% carboxymethylcellulose sodium salt
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: Test material dissolved in bi-distilled water containing 1% carboxymethylcellulose
sodium salt


Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
No data available
Duration of treatment / exposure:
11 days (from day 6 through day 17 post coitum)
Frequency of treatment:
Daily
Duration of test:
20 days
Doses / concentrations
Remarks:
0, 100, 300, 1000mg/kg bw/day
No. of animals per sex per dose:
Total: 88
0 mg/kgbw/day: 22 female
100 mg/kgbw/day: 22 female
300 mg/kgbw/day: 22 female
1000 mg/kgbw/day: 22 female
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Animals were checked twice daily for mortality/morbidity, and once daily for clinical signs.
- Cage side observations checked in table [No.?] were included.

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations: body weight were recorded at designated intervals during pregnancy


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes :Food consumption were recorded at designated intervals during
pregnancy

- 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): Yes / No / No data
- Time schedule for examinations:

POST-MORTEM EXAMINATIONS: Yes / No / No data
- Sacrifice on gestation day #
- Organs examined:

OTHER:
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other:
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No data
Statistics:
No data available
Indices:
No data available
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Clinical signs were restricted to discoloration of urine and faeces.
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
All animals survived until caesarean section
Body weight and weight changes:
no effects observed
Description (incidence and severity):
body weighty were not affected by the test substance administration
Food consumption and compound intake (if feeding study):
no effects observed
Description (incidence and severity):
Food consumption were not affected by the test substance administration
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
Gross pathological findings:
no effects observed
Description (incidence and severity):
No abnormal macroscopically findings were noted during necropsy
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Maternal developmental toxicity

Number of abortions:
not specified
Pre- and post-implantation loss:
no effects observed
Total litter losses by resorption:
no effects observed
Early or late resorptions:
no effects observed
Dead fetuses:
no effects observed
Changes in pregnancy duration:
not specified
Changes in number of pregnant:
not specified
Other effects:
no effects observed
Description (incidence and severity):
The differences amongst the relevant reproduction data (post-implantation loss, number of implantations and foetuses) of the vehicle control group and the dose groups gave no indication of test article related effects.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
body weight and weight gain
clinical signs
early or late resorptions
food consumption and compound intake
gross pathology
mortality
pre and post implantation loss
total litter losses by resorption
Remarks on result:
other: No effects on reproductive performance

Maternal abnormalities

Abnormalities:
not specified
Localisation:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
The mean body weights of foetuses gave no indication of effects caused by administration of the test article.
Reduction in number of live offspring:
not specified
Changes in sex ratio:
no effects observed
Description (incidence and severity):
the ratio of male and female foetuses gave no indication of effects caused by administration of the test article.
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
The external examinations of foetuses gave no indication of effects caused by administration of the test article.
Skeletal malformations:
no effects observed
Description (incidence and severity):
The skeletal examinations of foetuses gave no indication of effects caused by administration of the test article.
Visceral malformations:
no effects observed
Description (incidence and severity):
The visceral examinations of foetuses gave no indication of effects caused by administration of the test article.
Other effects:
not specified

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
not specified
Basis for effect level:
reduction in number of live offspring
changes in sex ratio
fetal/pup body weight changes
external malformations
skeletal malformations
visceral malformations
Remarks on result:
other: No developmental toxic effects were observed

Fetal abnormalities

Abnormalities:
not specified
Localisation:
other: not specified

Overall developmental toxicity

Developmental effects observed:
not specified
Treatment related:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 1000 mg/kg bw/day for F0 and F1 generation female wistar rats when treated with test material by oral gavage.
Executive summary:

The teratogenic toxicity study was performed according to OECD 414 guideline. The pregnant female wistar rats were treated with test material in dose concentration 0, 100, 300, 1000 mg/kg bw/day by oral gavage route from day 6 through day 17 post coitum.22 pregnant female /dose group were received test material while a group of 22 pregnant rats received the vehicle only (bi-distilled water containing 1% carboxymethylcellulose sodium salt) and served as a control group. Animals were checked twice daily for mortality/morbidity, and once daily for clinical signs. Food consumption and body weight were recorded at designated intervals during pregnancy. On day 21 post coitum, the animals were killed and examined macroscopically. Foetuses were removed by caesarean section.

All animals survived until caesarean section and with the exception of violet discoloured urine, faeces and bedding material observed in all dosage groups, no reaction to treatment or clinical signs were observed in any female. Food consumption and body weighty development were not affected by the test material administration. No abnormal macroscopically findings were noted during necropsy. The differences amongst the relevant reproduction data (post-implantation loss, number of implantations and foetuses) of the vehicle control group and the dose groups gave no indication of test article related effects. The mean body weights of foetuses, the ratio of male and female foetuses and the results of external, visceral and skeletal examinations of foetuses gave no indication of effects caused by administration of the test material. Hence, NOAEL was considered to be 1000 mg/kg bw/day for F0 and F1 generation female wistar rats when treated with test material by oral gavage.