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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, basic data given (e.g. results tables are provided), acceptable for assessment
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1973
Report Date:
1973

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
FDA-Compound 71-45 ("sodium silicoaluminate")

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no
- Housing: single
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Photoperiod (hrs dark / hrs light): no data


Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: water suspension

VEHICLE
- Justification for use and choice of vehicle (if other than water): used as dispersant
- Concentration in vehicle: maximum 1500 - 1600 mg NAS/6.4 mL water => 10 mL suspension/kg bw
- Amount of vehicle (if gavage): adjusted to the dose (see Appendix I, p. 21), from 1 mL water/kg bw to 6.4 mL water/kg bw
Analytical verification of doses or concentrations:
no
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: no data
- Length of cohabitation: no data
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
Duration of treatment / exposure:
from day 6 to day 15 of gestation
Frequency of treatment:
1x/d
Duration of test:
Gestation day 20: sacrifice of all dams by Caesarian section
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 16, 74, 350 and 1600 mg/(kg*d) (as aqueous suspension)
Basis:
nominal conc.
No. of animals per sex per dose:
21 - 23 pregnant female rats
Control animals:
yes, concurrent vehicle
other: positve control dosed with Aspirin (250 mg/kg bw)
Details on study design:
- Dose selection rationale: no data

Examinations

Maternal examinations:
BODY WEIGHT: Yes
- Time schedule for examinations: gestation day 0, 6, 11, 15, and 20


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes (not documented)
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes


POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
- Organs examined: in particular urogenital tract

Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: yes (neonatal pup weight) [Appendix II, p. 24]
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Number of early resorptions: No data
- Number of late resorptions: No data
Fetal examinations:
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: 1/3 per litter
- Skeletal examinations: Yes: 2/3 per litter
- Head examinations: yes
Statistics:
no data
Historical control data:
no data

Results and discussion

Results: maternal animals

Maternal developmental toxicity

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

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Remarks:
(highest dose tested)
Effect level:
1 600 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Effect levels (fetuses)

Dose descriptor:
NOAEL
Remarks:
(highest dose tested)
Effect level:
1 600 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

The administration of up to 1600 mg/kg (body weight) of the test material to pregnant rats for 

10 consecutive days had no clearly discernible effect on nidation or on maternal or fetal survival. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ
from the number occurring spontaneously in the sham-treated controls.

  

Applicant's summary and conclusion