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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on generations indicated in Effect levels (migrated information)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1983
Reliability:
2 (reliable with restrictions)

Data source

Reference
Reference Type:
publication
Title:
Toxicity of Sodium Bromide in Rats: Effects on Endocrine System and Reproduction
Author:
Van Leeuwen F.X.R., Den Tonkelaar E.M. and Van Logten M.J.
Year:
1983
Bibliographic source:
Fd. Chem. Toxic., 1983, Vol. 21 no 4, 383-389.

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: other
Principles of method if other than guideline:
Study was not based on standard protocol.
Every generation was mated twice (F0 generation mated 4 times):
F0 -> F1a, F1b (further mated), F1c (for transplacental Br transport study), F1d (reversibility study)
F1b -> F2a, F2b (further mated)
F2b -> F3a, F3b
Mating of F1 and F2 generations was not performed for the 4800 or 19200 mg/kg (diet)/day dose groups.


GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sodium bromide

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
no further details

Administration / exposure

Route of administration:
oral: feed
Vehicle:
other: Diet
Details on exposure:
In food
Plain diet
Details on mating procedure:
Study was not based on standard protocol.
Every generation was mated twice (F0 generation mated 4 times):
F0 -> F1a, F1b (further mated), F1c (for transplacental Br transport study), F1d (reversibility study)
F1b -> F2a, F2b (further mated)
F2b -> F3a, F3b
Mating of F1 and F2 generations was not performed for the 4800 or 19200 mg/kg (diet)/day dose groups.
Analytical verification of doses or concentrations:
no
Details on analytical verification of doses or concentrations:
no further details
Duration of treatment / exposure:
Exposure period: Three generations

Frequency of treatment:
Daily

Details on study schedule:
no further details
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 75, 300, 1200, 4800, 19200 ppm
Basis:
nominal in diet
No. of animals per sex per dose:
Males: 9-10 per group (F0) or 10 per group (F1, F2).
Females: 7-12 per group (F0), 14-19 per group (F1), 10 per group (F2)
Control animals:
yes, concurrent no treatment
Details on study design:
no further details
Positive control:
no

Examinations

Parental animals: Observations and examinations:
Unknown method


Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
300 ppm

Results: F1 generation

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
1 200 ppm

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOAEL
Generation:
F2
Effect level:
1 200 ppm

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

Result: Fertility was nil in the 19200 ppm group and were markedly reduced in the  480 ppm group. These effects were found to be reversible.



The author states that 300 ppm NaBr in feed corresponds to 12 mg (Br-)/kg bw/day.

Applicant's summary and conclusion

Conclusions:
Approximately equal numbers of male and female rats were allowed to breed whilst being administered sodium bromide (doses: 0, 75, 300, 1200, 4800 and 19200 ppm) in their feed. The subsequent F1 generation was allowed to breed resulting in an F2 generation which in turn was allowed to produce an F3 generation. Two litters were obtained at each generation (two additional litters at the F1 generation).
Fertility index, viability and lactation indexes were evaluated for each generation.
Pathological examinations were made including after 21 days for pups measuring body and organ weights.
The reversibility of the fertility effects in the highest dose group was also examined along with the effects of mating treated males with untreated females and vice versa.
No treatment-related effects on the breeding results were observed up to 1200 ppm. Fertility was nil in the 19200 ppm group and was markedly reduced in the 4800 ppm group. These effects were found to be reversible. In the latter group, the viability of the offspring was lower than in the other groups.
Microscopic examinations of all pups born during the entire experimental period provided no evidence of anomalies.
Executive summary:

Approximately equal numbers of male and female rats were allowed to breed whilst being administered sodium bromide (doses: 0, 75, 300, 1200, 4800 and 19200 ppm) in their feed. The subsequent F1 generation was allowed to breed resulting in an F2 generation which in turn was allowed to produce an F3 generation. Two litters were obtained at each generation (two additional litters at the F1 generation).

Fertility index, viability and lactation indexes were evaluated for each generation.

Pathological examinations were made including after 21 days for pups measuring body and organ weights.

The reversibility of the fertility effects in the highest dose group was also examined along with the effects of mating treated males with untreated females and vice versa.

No treatment-related effects on the breeding results were observed up to 1200 ppm. Fertility was nil in the 19200 ppm group and was markedly reduced in the 4800 ppm group. These effects were found to be reversible. In the latter group, the viability of the offspring was lower than in the other groups.

Microscopic examinations of all pups born during the entire experimental period provided no evidence of anomalies.