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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
Study period:
no data available
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well-documented study.

Data source

Reference
Reference Type:
publication
Title:
Teratologic Evaluation of Compound FDA 71-22, Sodium Metabisulfite in Rabbit
Author:
Anonymous
Year:
1974
Bibliographic source:
National Technical Information Service (NTIS), U.S. Department of Commerce, PB-267 194, July 1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
not specified
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Sodium metabisulfite, FDA 71-22
- Molecular formula (if other than submission substance): Na2S2O5
- Physical state: solid, white crystalline material
No further details are given.

Test animals

Species:
rabbit
Strain:
Dutch
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: virgin, adult
- Housing: individually housed in mesh bottom cages
- Diet: ad libitum
- Water: ad libitum
No further details are given.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Amount of vehicle (if gavage): doses administered as a water solution of 1 mL/kg body weight.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Details on mating procedure:
- Impregnation procedure: artificial insemination.
- On day 0, each doe was given an injection of 0.4 mL of human chorionic gonadotropin (400 IU) via the marginal ear vein.
- 3 hours later, each doe was inseminated artificially with 0.3 mL of diluted semen from a proven donor buck using approximately 20 x 10^6 motile sperm.
Duration of treatment / exposure:
from gestation day 6 to 18
Frequency of treatment:
daily
Duration of test:
until day 29 of gesation
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1.23 mg/kg body weight
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5.71 mg/kg body weight
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
26.5 mg/kg body weight
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
123 mg/kg body weight
Basis:
nominal conc.
No. of animals per sex per dose:
4 treatment groups with 15 to 20 mated females
Control animals:
yes, sham-exposed
other: 2.5 mg/kg body weight of 6-aminonicotinamide dosed on Day 9 (positive control)
Details on study design:
No further details are given.

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: all animals were observed daily for appearance and behaviour.

BODY WEIGHT: Yes
- Time schedule for examinations: recorded on days 0, 6, 12, 18 and 29 of gestation.

FOOD CONSUMPTION: Yes
- Time schedule: all animals were observed daily with particular attention to food consumption.

WATER CONSUMPTION: No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29
- Organs examined: all does were subjected to Caesaren section under surgical anesthesia.
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: Yes
- Number of implantations: Yes
- Number of resorptions: Yes
- Number and sex of live and dead fetuses: Yes
Fetal examinations:
External examinations: Yes
- Body weights of the live pups were recoded.
- All fetuses underwent a detailed gross examination for the presence of external congenital abnormalities.

Soft tissue examinations: Yes
- The live fetuses of each litter were then placed in an incubator for 24 hours for evaluation of neonatal survival.
- All surviving pups were sacrificed, and all pups examined for visceral abnormalities (by dissection).

Skeletal examinations: Yes
- All fetuses were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal defects (Sternebrae, Ribs, Vertebrae, Skull, Extremities and Miscellaneous)

Head examinations: No data

Statistics:
no data
Indices:
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

Details on maternal toxic effects:
- The pregnancy rates was comparable among groups and survival of pregnant females was not affected by treatment with sodium metabisulphite.
- Maternal body weights and weight gains were comparable among groups.
- There were no treatment-related effects on the number of abortions, corpora lutea, implantation sites, live litters and resorptions.




Effect levels (maternal animals)

open allclose all
Dose descriptor:
NOAEL
Effect level:
> 123 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Remarks on result:
not determinable
Remarks:
no NOAEL identified
Dose descriptor:
NOAEL
Effect level:
> 123 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
- The number of live and dead fetuses, sex ratio and average fetal weight was not affected by treatment of dams with sodium metabisulphite.
- 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.

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
> 123 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of up to 123 mg/kg bw/d of sodium metabisulphite to pregnant rabbits for 13 consecutive days had no clearly discernible effect on nidation or on maternal or foetal 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. Thus, the NOAEL for maternal and developmental toxicity can be expected above the highest dose of 123 mg/kg body weight sodium metabisulphite in this rabbit study.