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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well documented study which meets basic scientific principles.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1974
Reference Type:
publication
Title:
SIDS Initial Assessment Report For SIAM 15
Author:
OECD
Year:
2002
Bibliographic source:
OECD SIDS SODIUM BICARBONATE

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Female Wistar rats were treated with sodium bicarbonate by oral intubation at doses of 3.4, 15.8, 73.3 and 340 mg/kg from day 6-15 of gestation. On day 20 all dams were subjected to Caesarean section and the number of implantation sites, resorption sites and live and dead fetuses were recorded. One-third of the fetuses of each litter underwent detailed visceral examinationswhile the remainings examined for skeletal defects.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): sodium bicarbonate

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VOLUME
At a dosage level of < 250 mg/kg the test material was dosed at 1 mI/kg. At a dosage of 340 mg/kg the test material was dosed at 2 ml/kg.
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: data not given
- Length of cohabitation: data not given
- Further matings after two unsuccessful attempts: data not given
- Verification of same strain and source of both sexes: data not given
- Proof of pregnancy: vaginal plug referred to as day 0 of pregnancy
Duration of treatment / exposure:
day 6 - 15 of gestation
Frequency of treatment:
once daily
Duration of test:
20 days
Doses / concentrations
Remarks:
Doses / Concentrations:
3.4, 15.8, 73.3, 340 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
25
Control animals:
yes, sham-exposed
other: Aspirin: 250 mg/kg bw

Examinations

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

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: on days 0, 6,11, 15 and 20 of gestation

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

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 17
- Organs examined: urogenital tract
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No data
- Number of corpora lutea: No data
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
Fetal examinations:
- External examinations: Yes: 1/3rd per litter
- Soft tissue examinations: Yes: 1/3rd per litter
- Skeletal examinations: Yes: 1/3rd per litter
- Head examinations: Yes: No data

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
>= 340 mg/kg bw/day (nominal)
Basis for effect level:
other: developmental toxicity

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
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

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Results:

Sham Aspirin (250 mg/kg bw) Sodium bicarbonate (mg/kg bw)
3.4 15.8 73.3 340
Pregnancies 20 24 20 21 21 22
Died or aborted 1 0 0 0 0 0
Live litters 19 19 20 21 21 22
Implant sites 226 277 239 268 238 254
Resorptions 5 93 3 0 0 1
Live fetuses 221 183 236 268 237 251
Dead fetuses 0 1 0 0 1 2
Fetus weight (g) 3.57 2.53 3.66 3.8 3.85 3.72

Applicant's summary and conclusion