Reaction mass of calcium sulfate and potassium sulfate and sodium sulphate

Developmental toxicity / teratogenicity

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: see 'Remark'

Remarks:

No information was available about test substance. The test was not performed according to the standardized method and GLP. All test parameters were not reported. However, the study was well described with enough details and the results were validated in the OECD SIDS dossier.

Data source

Reference

Reference Type:

publication

Title:

Validation of an in vivo developmental toxicity screen in the mouse

Author:

SEIDENBERG JM, ANDERSON DG and BECKER RA

Year:

1986

Bibliographic source:

Terato., Carcino. and Muta., 6:361-374

Materials and methods

Test guideline

Qualifier:

no guideline available

Deviations:

not applicable

Principles of method if other than guideline:

Sodium sulfate was administered to time-pregnant ICR/SIM mice during organogenesis. A single dose level, at or near the level producing overt maternal toxicity in preliminary range-finding studies, was administered by gavage on gestation days 8 through 12.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium sulfate

IUPAC Name:

Sodium sulfate

Constituent 2

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

Na2SO4

IUPAC Name:

disodium sulfate

Details on test material:

- Name of test material: Sodium sulfate
- Substance type: no data
- Physical state: no data
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

mouse

Strain:

other: ICR/SIM

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories (Gilroy, CA)
- Age at study initiation: Adult
- Weight at study initiation: 32 to 36 g
- Fasting period before study: no data
- Housing: Pregnant mice were housed one per cage in 32 x 23 x 15 cm suspended polycarbonate shoebox cages containing hardwood-chip bedding
- Diet: Simonsen Custom Lab diet 7 ad libitum
- Water: UV-purified drinking water ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2°C
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod: 12/12-h light/dark photoperiod

IN-LIFE DATES:
No data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Distillated water

Details on exposure:

PREPARATION OF DOSING SOLUTIONS:
Dosages (1 to 1.4 mL/100 g body weight) were based on body weights at day 7 of gestation; mice were also weighed on day 13 and at 1 day postpartum.

DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): no data
- Storage temperature of food: no data

VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Lot/batch no. (if required): no data
- Purity: no data

Analytical verification of doses or concentrations:

no

Details on mating procedure:

Animals were received from the supplier timed-pregnant or were bred in-house, but no data was available about mating procedure. Pregnant mice were housed one per cage.
Nesting material of compressed cotton with poplar wood chips was provided to the females on day 13 of gestation.

Duration of treatment / exposure:

4 days (gestation day 8-12)

Frequency of treatment:

Once daily

Duration of test:

Up to day 22 of pregnancy

Doses / concentrations

Remarks:

Doses / Concentrations:
2800 mg/kg/day
Basis:
nominal in diet

No. of animals per sex per dose:

28

Control animals:

yes, concurrent vehicle

Details on study design:

A single minimally toxic dose expected to result in significant maternal weight reduction, up to 10% mortality, or other clinical signs of overt toxicity, was selected based on previous range-finding studies in nonpregnant female mice.

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes

FOOD CONSUMPTION AND COMPOUND INTAKE: No data

POST-MORTEM EXAMINATIONS: Yes
Dams that had not given birth by gestation day 21 or 22 were necropsied and their uteri were examined.

Ovaries and uterine content:

No data

Fetal examinations:

Neonates were examined, counted and weighed on the day of birth (day 1) and day 3.
Dead neonates were recovered from the nest and externally examined for abnormalities.

Statistics:

All analyses compared individual treatment groups and their concurrent controls.
Maternal body weight gain during treatment (day 13 minus day 7 weight) was assess by a two tailed analysis of variance.
A one-tailed analysis of variance was used to assess live and dead litter size data.
A one-tailed Fisher’s exact probability test was used to assess neonatal survival ratios.
Neonatal body weight was assessed by a two-tailed analysis of variance.
To correct for differences in litter size, the number of live neonates born was used as a covariant in the body weight analyzes.

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

Effect levels (maternal animals)

Dose descriptor:

NOEL

Effect level:

2 800 mg/kg bw/day (nominal)

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:not examined

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Compared to controls, slight increase in neonatal body weight at day 1 post-partum.

Normal maternal weight gain

Normal delivery rate

Normal litter size

Normal number of live births

Normal weight pups on day 3

No macroscopic visceral or skeletal abnormalities

Applicant's summary and conclusion

Conclusions:

Sodium sulfate has no effect on the development in the mouse

Executive summary:

In a developmental toxicity study,Sodium sulfate was administered to 28 mice ICR/SIM females by gavage at dose levels of 2800 mg/kg bw/day from days 8 through12 of gestation.

No treatment-related effects in mortality, clinical signs, body weight, food consumption, or caesarean parameters.

No treatment-related effects in developmental parameters.