Calcium bromide

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:

weight of evidence

Study period:

1995

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium bromide

EC Number:

231-599-9

EC Name:

Sodium bromide

Cas Number:

7647-15-6

IUPAC Name:

sodium bromide

Details on test material:

99.84 % Sodium bromide
Batch no. 940045
White crystalline solid
Stability of formulations: at least 7 days

Test animals

Species:

rat

Strain:

other: crl: CD® BR VAF/Plus strain

Details on test animals or test system and environmental conditions:

no further details

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

no further details

Analytical verification of doses or concentrations:

no

Details on analytical verification of doses or concentrations:

no further details

Details on mating procedure:

no further details

Duration of treatment / exposure:

days 6 to 15 post mating

Frequency of treatment:

Daily

Duration of test:

20 days after pregnancy

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 300 and 1000 mg/kg bw
Basis:
nominal in diet

No. of animals per sex per dose:

25

Control animals:

yes

Details on study design:

Sex: female
Duration of test: 20 days

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:yes

Details on maternal toxic effects:
Treatment at 1000 mg/kg bw/day was associated with unsteady gait, feet falling through cage grid floor, poorly coordinated movements, reduced bodytone and hair loss. There was one mortality at this dose level. Lower bodyweight gains were observed during days 6 to 12 and 16 to 20 of pregnancy. Increased food consumption was observed during days 6-9 and 14-15, followed by lower food consumption during days 18-19.
Treatment at 300 mg/kg bw/day was associated with lower bodyweight gains during days 16-20 of pregnancy.
Treatment at 100 mg/kg bw/day was not associated with any observable maternal responses.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
There were no adverse effects on any of the litter parameters recorded for any of the dose groups.
Detailed examination of foetal morphology from dams treated at 1000 mg/kg bw/day revealed higher incidences of foetuses/litters showing absent left kidney, absent left ureter, absent/narrow left uterine horn, distorted ribs, shortened/absent 13th ribs, irregular ossification of the thoracic vertebral centra, reduced and/or unossified sternebrae and reduced ossification of one or more cranial centres than in controls.
In the 300 mg/kg bw/day dose group, detailed examination of the foetal morphology revealed a higher incidence of foetuses showing reduced ossification of various components of the skeleton compared with controls.
Treatment at 100 mg/kg bw/day was not associated with any observable adverse effects on or in utero development of the conceptus.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day

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

Result: The test substance showed developmental toxicity at 300 and 1000 mg/kg bw/day. Test result is equivalent to: NOAEL = 77.6 mg(Br-)/kg bw/day for the bromide ion

Applicant's summary and conclusion

Conclusions:

Maternal: 1000 mg/kg bw/day – 1 mortality, unsteady gait, feet falling through cage grid floor, poorly coordinated movements, reduced bodytone and hair loss. Periodically reduced body weight gains.
300 mg/kg bw/day – lower bodyweight gains
Foetal: 1000 mg/kg bw/day – higher incidences of foetuses/litters showing urogenital changes and skeletal abnormalities.
300 mg/kg bw/day – foetal morphology: higher incidence of foetuses showing reduced ossification of various components of the skeleton