Dipotassium disulphate

Developmental toxicity / teratogenicity

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: This study was selected as the key study because the information provided for the hazard endpoint is sufficient for the purpose of classification and labelling and/or risk assessment. non-standard screening test.

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:

Teratogen., Carcinogen. Mutagen., 6:361-374

Materials and methods

Principles of method if other than guideline:

As part of a validation of a developmental screen, pregnant mice were exposed to 55 compounds, composed of known teratogens, known non-teratogens or equivocal substances.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

IUPAC Name:

disodium sulfate

Details on test material:

- Purity: not reported

Test animals

Species:

mouse

Strain:

other: ICR/SIM

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories
- Age at study initiation: adult
- Weight at study initiation: 32 to 36 g
- Housing: housed one per cage in 32 X 23 X 15 cm suspended polycarbonate shoebox cages
- Diet (e.g. ad libitum): Simonsen Custom Lab Diet 7 ad libitum
- Water (e.g. ad libitum): UV-purified drinking water ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± ºC
- Photoperiod (hrs dark / hrs light): 12-hr-on, 12-hr-off light cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Single daily dose by gavage; dose level at or near induction of maternal toxicity.

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Impregnation procedure: Mice were either received from the supplier timed-pregnant or (because of the low pregnancy rate in many shipments of these animals) were bred in-house.
- Proof of pregnancy: gestation day 1 = day plug found

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:
actual ingested
test material

No. of animals per sex per dose:

28

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

Maternal weight gain, delivery rate, litter size, % live births, pup weight on day 1 and day 3 were examined.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
- Examinations included: Dams that had not given birth by gestation day 21 or 22 were necropsied and their uteri were examined.

Fetal examinations:

Neonatal survival rate, macroscopic visceral and skeletal abnormalities were examined.

Statistics:

Maternal weight: two-tailed analysis of variance live and dead litter size: one-tailed analysis of variance neonatal survival rate: Fisher one-tailed exact probability.
Neonatal weight: two-tailed analysis of variance with litter size as co-variant.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Normal maternal weight gain, normal delivery rate, normal litter size, normal number of live births.

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

2 800 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

2 800 mg/kg bw/day

Based on:

test mat.

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Compared to controls, slight increase in neonatal body weight at day 1 p.p. (1.80+0.14 vs 1.72 + 0.13 grams). Normal weight of pups on day 3, no macroscopic visceral or skeletal abnormalities. The slight increase in body weight of neonates on day 1 p.p. only is not an adverse effect and is not biologically relevant.

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

This study and the conclusions which are drawn from it fulfil the quality criteria (validity, reliability, repeatability).
NOAEL (maternal toxicity) = 2800 mg/kg bw/ day
NOAEL (developmental toxicity) = 2800 mg/kg/bw/ day

Normal maternal weight gain, normal delivery rate, normal litter size, normal nr. of live births.
Compared to controls, slight increase in neonatal body weight at day 1 p.p. (1.80+0.14 vs 1.72 + 0.13 grams). Normal weight of pups on day 3, no macroscopic visceral or skeletal abnormalities.
The slight increase in body weight of neonates on day 1 p.p. only is not an adverse effect and is biologically totally irrelevant.

Executive summary:

The developmental effects of the test substance in the mouse were examined as part of a validation effort of a developmental screening test. The test substance was administered (2800 mg/kg/day) by gavage on gestation days 8 through 12. Females were allowed to deliver, and neonates were examined, counted, and weighed on the day of birth (day 1) and day 3. No mortality, an unchanged average weight gain, and normal number of litters and neonates/litter were found. No effect on maternal body weight was observed. A 100% perinatal survival was found, with an increased postnatal weight at day 1, and normal weight at day 3 in the absence of externally visible abnormalities.