Calcium bromide

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

1974

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Semichronic Toxicity Study of Sodium Bromide in Rats

Author:

Van Logten M.J., Wolthius M., Rauws A.G., Kroes R., Den Tonkelaar E.M., Berkvens H. and van Esch G.J.

Year:

1974

Bibliographic source:

Toxicology, 2 (1974), 257-267

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

No guidelines available at that time

GLP compliance:

no

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

Test animals

Species:

rat

Strain:

other: Wistar SPF

Sex:

male/female

Administration / exposure

Route of administration:

oral: feed

Duration of treatment / exposure:

90 days

Frequency of treatment:

Daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 75, 300, 1200, 4800 or 19200 ppm
Basis:

Control animals:

yes, concurrent vehicle

Details on study design:

Post-exposure period: None

Results and discussion

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

300 ppm

Based on:

other: equivalent to 15 mg Br/kg bw/day

Sex:

male/female

2

Dose descriptor:

LOAEL

Effect level:

1 200 ppm

Based on:

other: equivalent to 62 mg Br/kg bw/day

Sex:

male/female

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The test substance was administered in the diet for 90 days to 5 groups of rats (10 rats per sex per dose group) at levels of 0, 75, 300, 1200, 4800 or 19200 ppm. Clinical toxicological signs and body weights were noted weekly and haematological, clinical chemistry and urinalysis measurements were made between weeks 10 and 13 of the 90 day period. Complete necropsies were performed on surviving animals at study end. Histopathological examinations were performed on the major organs/tissues.
Animals in the 19200 ppm dose group did not groom themselves sufficiently and exhibited signs of motor incoordination. The male animals in this group showed significant growth retardation. Plasma bromide levels increased within 3 weeks to a plateau. In all groups, except in the highest dosage group, these plateaus were directly proportional to the bromide concentrations in the diets, as were the bromide concentrations in the brain and kidneys after 90 days. Total molar halogen concentration in plasma, however, remained constant throughout the investigation. No striking effects on haematological and biochemical parameters were seen except for a doubling of the percentage of neutrophil granulocytes in the highest dosage group. In female animals on 1200, 4800 and 19200 ppm and in male animals on 19200 ppm bromide an increase of relative thyroid weight was found. In male rats an increase of the relative weight of the adrenals was found in the 19200 ppm group and a decrease of relative prostate weight was seen in the two highest dosage groups. Histopathologically a dose-related disturbance of the endocrine system and some of its target organs was found. One animal was sacrificed prior to the end of the 90 days for humane reasons. No other mortality occurred.
1.1.1 LO(A)EL
1200 ppm (equivalent to a minimum of 62 mg (Br-)/kg bw/day)) (increased relative thyroid weight)
1.1.2 NO(A)EL
300 ppm (equivalent to a minimum of 15 mg (Br-)/kg bw/day))