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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
Study period:
not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Teratologic evaluation of FDA 71-20 (sodium bisulfite).
Author:
Anonymous
Year:
1972
Bibliographic source:
PB-221788, National Technical Information Service (NTIS), U.S. Department of Commerce, East Orange, New Jersy, USA

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium hydrogensulfite
EC Number:
231-548-0
EC Name:
Sodium hydrogensulfite
Cas Number:
7631-90-5
Molecular formula:
NaHSO3
IUPAC Name:
sodium hydrogen sulfite
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Sodium bisulfite
- Physical state: solid, white crystalline material
Specific details on test material used for the study:
not specified

Test animals

Species:
mouse
Strain:
CD-1
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: virgin, adult female mice
- Housing: individually housed in disposable plastic cages
- Diet (ad libitum)
- Water (ad libitum): fresh tap water

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
VEHICLE
- Amount of vehicle (if gavage): test item was administered as a water solution (1 mL/kg of 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: cohoused; females were mated with young adult males.
- Proof of pregnancy: vaginal sperm plug was considered day 0 of gestation.
Duration of treatment / exposure:
gestation day 6 to 15
Frequency of treatment:
daily
Duration of test:
until Day 17 of gestation
Doses / concentrationsopen allclose all
Dose / conc.:
2 mg/kg bw/day (actual dose received)
Dose / conc.:
7 mg/kg bw/day (actual dose received)
Dose / conc.:
32 mg/kg bw/day (actual dose received)
Dose / conc.:
150 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
23 to 24 mated females
Control animals:
yes, sham-exposed
other: 150 mg/kg body weight Aspirin (positive control)
Details on study design:
No further details are given.

Examinations

Maternal examinations:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations checked: mortality, appearance and behaviour

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: days 0, 6, 11, 15 and 17 of the gestation period.

FOOD CONSUMPTION: Yes
- Time schedule: daily

WATER CONSUMPTION: No data

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 17
- all animals were subjected to Caesarian 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 of live and dead foetuses: Yes
Fetal examinations:
External examinations: Yes
- All foetuses underwent a gross examination for the presence of external congenital abnormalities. .

Soft tissue examinations: Yes
- One-third of the foetuses of each litter underwent detailed visceral examinations employing 10x magnification.

Skeletal examinations: Yes
- Two-third of the foetuses 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

- Body weights of the live pups were recoded.
- Sex of the foetuses was recorded
Statistics:
not specified
Indices:
not specified
Historical control data:
not specified

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
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:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
- The survival of pregnant females was not affected by treatment with sodium bisulfite.
- Maternal body weights and weight gains were comparable among groups.

Maternal developmental toxicity

Number of abortions:
no effects observed
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
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Effects on pregnancy duration" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsMaternalAnimals.MaternalDevelopmentalToxicity.EffectsOnPregnancyDuration): not specified
Changes in number of pregnant:
no effects observed
Other effects:
not specified
Details on maternal toxic effects:
- The pregnancy rates was comparable among groups (control group: 20 pregnant mice; 2.0 mg/kg bw/d: 21 pregnant mice; 7.0 mg/kg bw/d: 21 pregnant mice; 32.0 mg/kg bw/d: 21 pregnant mice; 150 mg/kg bw/d: 21 pregnant mice).
- There were no treatment-related effects on the number of abortions, corpora lutea, implantation sites, live litters and resorptions.

Effect levels (maternal animals)

Key result
Remarks on result:
not determinable due to absence of adverse toxic effects

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
no effects observed
Changes in sex ratio:
no effects observed
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
not specified
Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
- The number of live and dead foetuses, sex ratio and average foetal weight was not affected by treatment of dams with sodium bisulfite.
- 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)

open allclose all
Key result
Dose descriptor:
NOAEL
Remarks:
teratogenicity
Remarks on result:
not determinable due to absence of adverse toxic effects
Key result
Dose descriptor:
NOAEL
Remarks:
developmental toxicity
Remarks on result:
not determinable due to absence of adverse toxic effects

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The administration of up to 150 mg/kg bw/d of sodium bisulfite to pregnant mice for 10 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 150 mg/kg body weight sodium bisulfite in this mice study.