Reaction mass of ammonium sulphate and potassium sulfate and sodium sulphate

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

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given

Data source

Reference

Reference Type:

publication

Title:

Validation of an in Vivo Developmental Toxicity Screen in the Mouse.

Author:

Seidenberg JM et al.

Year:

1986

Bibliographic source:

Teratogenesis, Carcinogenesis, and Mutagenesis 6: 361-374.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Screening test with 55 chemicals, in which mice were dosed by oral intubation on days 8 through 12 of gestation (day 1 = day plug found). Mice were allowed to deliver, and 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.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

7727-73-3

EC Number:

616-445-4

Cas Number:

7727-73-3

IUPAC Name:

7727-73-3

Constituent 2

Reference substance name:

Sodium sulphate

EC Number:

231-820-9

EC Name:

Sodium sulphate

Cas Number:

7757-82-6

Molecular formula:

O4S.2Na

IUPAC Name:

sodium sulfate

Constituent 3

Reference substance name:

disodium sulfate decahydrate

IUPAC Name:

disodium sulfate decahydrate

Details on test material:

Sodium sulfate; no further data

Test animals

Species:

mouse

Strain:

ICR

Details on test animals or test system and environmental conditions:

TEST ANIMALS
adult barrier-reared ICR/SIM mice
- Source: Simonsen Laboratories (Gilroy, CA)
- Weight at study initiation: 32 - 36 g
- Housing: individually in 32 X 23 X 15 cm suspended polycarbonate shoebox cages
- Diet (ad libitum): Simonsen Custom Lab Diet 7
- Water (ad libitum): UV purified drinking water
Mice were either received from the supplier timed-pregnant or were bred in-house.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Analytical verification of doses or concentrations:

not specified

Details on mating procedure:

- Proof of pregnancy: vaginal plug referred to as day 1 of pregnancy

Duration of treatment / exposure:

days 8 through 12 of gestation

Frequency of treatment:

daily

Duration of test:

until day 3 post partum

Doses / concentrations

Remarks:

Doses / Concentrations:
2800 mg/kg bw/d
Basis:
actual ingested

No. of animals per sex per dose:

28 females per group

Control animals:

yes, concurrent vehicle

Examinations

Maternal examinations:

CAGE SIDE OBSERVATIONS: No data


DETAILED CLINICAL OBSERVATIONS: No data
- Time schedule:

BODY WEIGHT: Yes
- Time schedule for examinations: days 7 and 13 of gestation, day 1 post partum

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

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes, for dams not given birth by gestation day 21 or 22

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 assessed by a two-tailed analysis of variance. A one-tailed analysis of variance was used to assess live and dead litter size data. The calculation of the average live litter size on days 1 and 3 and the average number of neonates found dead per litter on day 1 included only those litters that were born. Litters that were alive in utero at necropsy and those that were completely resorbed will be discussed as appropriate, but were not included in this average. 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 analyses.

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

1

Dose descriptor:

NOAEL

Effect level:

2 800 mg/kg bw/day (actual dose received)

Basis for effect level:

other: maternal toxicity

2

Dose descriptor:

NOAEL

Effect level:

2 800 mg/kg bw/day (actual dose received)

Basis for effect level:

other: developmental toxicity

Results (fetuses)

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

2 800 mg/kg bw/day (actual dose received)

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

No evidence of maternal toxicity (mortality, body weight gain), or increased resorption rates was found. The test substance had no effects on pup survival, and no adverse developmental effects were observed. When compared to vehicle controls, birth weight was significantly increased. All of the confirmed teratogens tested in this study resulted in decreased live-born litter size.

Table: Maternal and perinatal effects of sodium sulphate

Treatment

Maternal response

Perinatal response

Average neonatal weight (g +/- SD)

Compound

Dose (mg/kg/d)

No. dead/ No. treated

Average weight gain (g+/-SD)

No. of litters

Average no. of neonated/litter (+/- SD)

% survival days 1-3

day 1

day 3

2-day gain

born

resorbed

live day 1

dead day 1

live day 3

Vehicle

---

0/28

8.5 +/- 1.7

25

0

13.3 +/- 3.8

0.16 +/- 0.5

13.2 +/- 3.8

99

1.72 +/- 0.13

2.42 +/- 0.25

0.70 +/- 0.15

Test substance

2800

0/28

8.6 +/- 1.7

24

0

12.9 +/- 2.5

0.04 +/- 0.2

12.8 +/- 2.4

100

1.80 +/- 0.14 *

2.58 +/- 0.29

0.78 +/- 0.18

* p<0.05

Applicant's summary and conclusion

Executive summary:

Oral administration of sodium sulphate, 2800 mg/kg bw/d to pregnant ICR mice on gd 8 - 12 did not produce maternally toxic or embryo-/fetotoxic effects nor teratogenic effects when compared with concurrent vehicle controls. Confirmed teratogens which were also tested in this study resulted in decreased live-born litter size.