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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:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Version / remarks:
1981
GLP compliance:
yes
Remarks:
CIBA-GEIGY Limited, Short-/Long-term Toxicology Facility, Reproduction Toxicology, 4332 Stein, Switzerland
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
EC Number:
248-421-0
EC Name:
Disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
Cas Number:
27344-41-8
Molecular formula:
C28H22O6S2.2Na
IUPAC Name:
disodium 2,2'-([1,1'-biphenyl]-4,4'-diyldivinylene)bis(benzenesulphonate)
Details on test material:
- Name of test material (as cited in study report): FAT 65029/G
- Physical state: Fine granulate, off-white
- Analytical purity: 86.4%
- Lot/batch No.: EN 372980 Op. 247/248
- Storage condition of test material: Room temperature, light-protected

Test animals

Species:
rat
Strain:
other: albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Animal Production, WST-455, CIBA-GEIGY Limited, 4332 Stein, Switzerland
- Age at study initiation: about 2 months
- Weight at study initiation: about 200 g
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 50±20
- Air changes (per hr): about 16
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 0.5 % aqueous solution of sodium carboxymethylcellulose
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: The test article-vehicle mixtures were prepared fresh daily.
The test article was mixed with the vehicle (0.5% CMC) and ground in a pestle and mortar; mixtures were kept light-protected. During administration the homogeneity of the test article mixtures was maintained by means of a magnetic stirrer.
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: 3/1
- Length of cohabitation: overnight
- Further matings after two unsuccessful attempts: no
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy = "day 0" post coitum (p.c)
Duration of treatment / exposure:
day 6 to day 15 of gestation
Frequency of treatment:
daily
Duration of test:
until day 21 p.c
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 1000 mg/kg bw
Basis:
actual ingested
No. of animals per sex per dose:
24 dams per dose
Control animals:
yes, concurrent vehicle
Details on study design:
- Dose selection rationale: The dose levels were selected based on a dose range-finding study with the test article in pregnant rats (Test
Number 915001)

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

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

BODY WEIGHT: Yes
- Time schedule for examinations: data

FOOD CONSUMPTION: Yes
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Organs examined: main organs of the thoracic and abdominal cavities, in particular the genitals

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
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter
- Head examinations: Yes: all per litter
Statistics:
Statistical analysis of continuous data are performed using the Analysis of Variance Procedure (ANOVA) followed by Dunnett's t-Test in case of a significant result in the ANOVA. Categorical data are analysed using Chi-Square test followed by Fisher's Exact test in case of a significant result in the Chi-Square test.
Non-parametric data are analysed using the Kruskal-Wallis nonparametric analysis of variance test followed by Mann-Whitney U-test.
In the present study, with only one treated group, these blocking tests are equivalent to t-test, Mann-Whitney U and Chi-square, for continuous, categorical and non-parametric data respectively.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
There were no remarkable cage-side observations during the study. Maternal body weights and food consumption were not affected by treatment. All animals survived to necropsy on day 21 p.c, except for one dam in the treated group, found dead on day 15 p.c. Necropsy revealed no pathological findings in this or any other animal.
Three animals in the control group were not pregnant, and one in the treated group died on day 15 p.c. Thus the number of pregnant animals with viable fetuses at necropsy was 21 and 23 for the control and treated group respectively. The number of implantation sites and preimplantation losses were comparable in the two groups. Early resorption rate was not affected by treatment, and there were no late resorptions, abortions or dead fetuses. Thus the number of viable fetuses was comparable in the two groups.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Fetal sex ratios and body weights were not affected by treatment.
There were no treatment-related fetal external, visceral, or skeletal abnormalities.

Effect levels (fetuses)

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: embryotoxicity
Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In the present study, the test article was not toxic to dams or fetuses at the limit dose of 1000 mg/kg. There was no evidence for embryotoxic or teratogenic potential. The no observed effect level of FAT 65'029/G for rat dams and fetuses in this study was 1000 mg/kg body weight/day.

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