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EC number: 231-599-9 | CAS number: 7647-15-6
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Toxicity to reproduction
Administrative data
- Endpoint:
- three-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 983
Materials and methods
- Principles of method if other than guideline:
- Male and female Wistar rats received 0, 75, 300, 1200, 4800 and 19200 mg NaBr in the diet during three successive generations. The study was designated to evaluate the reproductive and developmental effects of sodium bromide in multiple generations as well as the effect on the thyroid function in the parental animals.
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- Sodium bromide
- EC Number:
- 231-599-9
- EC Name:
- Sodium bromide
- Cas Number:
- 7647-15-6
- Molecular formula:
- BrNa
- IUPAC Name:
- Active bromine generated from sodium bromide and sodium hypochlorite
- Details on test material:
- - Name of test material (as cited in study report): sodium bromide
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: 4 months.
Administration / exposure
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on mating procedure:
- Male rats of proven fertility were mated with females.
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Three generations.
- Frequency of treatment:
- Daily.
- Details on study schedule:
- In three successive generations, at least two litters per female rat were raised. In the first generation a third litter was raised for the investigation of the transplacental transport of bromide. Furthermore, an additional litter was bred with parent animals of the highest dose group which were changed to the control diet in order to investigate the reversibility of the observed effects.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 75, 300, 1200, 4800 and 19200 mg NaBr/kg diet.
Basis:
nominal in diet
- No. of animals per sex per dose:
- Males: 9-10 animals/dose group.
Females: 7-11 animals/dose group (F0); 14-19 animals/dose group (F1); 10 animals/dose group (F2). - Control animals:
- yes, plain diet
- Details on study design:
- Because of the diminished fertility in the two highest dose groups, second and third generations were bred only from the groups dosed with sodium bromide up to 1200 mg/kg diet.
- Positive control:
- None.
Examinations
- Parental animals: Observations and examinations:
- CLINICAL OBSERVATIONS: Yes.
BODY WEIGHT: Yes.
OTHER:
HAEMATOLOGY: haematological examinations were carried out 3 weeks before each mating and directly after the weaning of the last litter.
THYROID FUNCTION: the thyroid hormone (T4) concentration in serum was determined in parent animals of the F0 generation. - Oestrous cyclicity (parental animals):
- No data.
- Sperm parameters (parental animals):
- No data.
- Litter observations:
- PARAMETERS EXAMINED
The following parameters were examined: number and sex of pups, viability, presence of gross anomalies, body weight and bromide ion levels in foetal kidneys. - Postmortem examinations (parental animals):
- ORGAN WEIGHTS
The tissues indicated in Table 2 were weighed: adrenals, thyroid, pituitary, ovaries, uterus, testes, prostate. - Postmortem examinations (offspring):
- ORGAN WEIGHTS
The tissues indicated in Table 2 were weighed: adrenals, thyroid, pituitary, ovaries, uterus, testes, prostate. - Statistics:
- No data.
- Reproductive indices:
- Fertility index (no. of pregnancies x 100/no. of matings).
- Offspring viability indices:
- Viability index (no. of pups alive at day 5 x 100/no. of pups born alive); Lactation index (no. of pups alive at day 21 x 100/no. of pups alive at day 5).
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- not examined
- Other effects:
- not examined
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- effects observed, treatment-related
- Description (incidence and severity):
- (≥ 4,800 mg/kg)
Details on results (P0)
Body weight determinations did not reveal a clear pattern of dose-related effects.
REPRODUCTIVE PERFORMANCE (PARENTAL ANIMALS)
The fertility was nil in the 19,200-mg group and was markedly reduced in the 4,800-mg group. The reversibility of the effects on reproduction was studied in parent animals fed a diet containing 19,200 mg NaBr/kg for 7 months followed by a control diet for 3 months before mating. The results were as follows: fertility index, 62%; viability index, 61%; lactation index, 90%. Although the viability was lower than in the control and lower dose groups, the fertility index and lactation index were similar.
ORGAN WEIGHTS (PARENTAL ANIMALS)
Organ-weight determinations did not reveal a clear pattern of dose-related effects in the successive generations. Only the adrenals of the females of the F0-generation showed a dose-dependent decrease in relative weight.
OTHER FINDINGS (PARENTAL ANIMALS)
HAEMATOLOGY: it was found a dose-related increase of the bromide levels in plasma, placenta and kidneys.
THYROID FUNCTION: a decrease in thyroid hormone (T4) concentration was found in the serum of the parent animals of the P-generation. The no-effect level for thyroid function was fixed at 300 mg/kg. This finding is indicative of an inhibitory action of bromide on the synthesis of thyroid hormones.
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- (reproductive)
- Effect level:
- 1 200 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on fertility index (equivalent to 120 and 60 mg/kg b.w./day for young and older rats, respectively).
- Dose descriptor:
- NOAEL
- Remarks:
- (developmental)
- Effect level:
- 1 200 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on viability index (equivalent to 120 and 60 mg/kg b.w./day for young and older rats, respectively).
- Remarks on result:
- other: Generation: F1, F2 (migrated information)
- Dose descriptor:
- NOAEL
- Remarks:
- (systemic)
- Effect level:
- 300 mg/kg diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Based on thyroid function (equivalent to 30 and 15 mg/kg b.w./day for young and older rats, respectively).
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- (≥ 4,800 mg/kg)
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Details on results (F1)
In the 4,800-mg group the viability of the offspring was lower than in the other groups. In this group, the viability of the young was greater in the second litter than in the first. Furthermore, during lactation of the first litter all of the young alive at day 5 died before day 21. In the second litter of this group, however, all animals alive at day 5 were still alive at day 21.
BODY WEIGHT (OFFSPRING)
Body weight determinations did not reveal a clear pattern of dose-related effects.
ORGAN WEIGHTS (OFFSPRING)
Organ-weight determinations given in Table 2 did not reveal a clear pattern of dose-related effects.
BROMIDE CONCENTRATIONS
The bromide levels in foetal kidneys demonstrate that foetuses in utero were exposed to bromide, since the concentration of bromide in the kidneys corresponding dams and foetuses is almost equal.
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Table 1. Breeding results in reproduction study on sodium bromide fed to rats at dietary levels up to 19200 mg/kg.
|
Values for groups fed NaBr at dietary levels (mg/kg) of: |
|||||
Generation |
0 |
75 |
300 |
1200 |
4800 |
19200 |
|
Fertility index* |
|||||
F0 |
70 |
70 |
72 |
65 |
25 |
0 |
F1 |
62 |
54 |
44 |
53 |
- |
- |
F2 |
52 |
67 |
80 |
45 |
- |
- |
|
Viability index* |
|||||
F0 |
90 |
98 |
96 |
92 |
32, 61+ |
- |
F1 |
92 |
88 |
80 |
97 |
- |
- |
F2 |
96 |
98 |
93 |
98 |
- |
- |
|
Lactation index* |
|||||
F0 |
95 |
96 |
95 |
94 |
0, 100+ |
- |
F1 |
93 |
85 |
72 |
80 |
- |
- |
F2 |
99 |
99 |
99 |
99 |
- |
- |
|
Mean body weight at day 21 |
|||||
F0 |
40 |
45 |
43 |
43 |
-, 38+ |
- |
F1 |
41 |
43 |
40 |
38 |
- |
- |
F2 |
36 |
38 |
38 |
36 |
- |
- |
*Fertility index = no. of pregnancies x 100/no. of matings; viability index = no. of pups alive at day 5 × 100/no. of pups born alive; lactation index = no. of pups alive at day 21 × 100/no. of pups alive at day 5.
+ Data are given separately for first and second litter.
Table 2. Reproduction study in rats fed sodium bromide at dietary levels up to 4800 mg/kg: mean body weights and relative organ weights determined at the end of each generation.
Generation |
Parameter+ |
|
Values for groups fed NaBr at dietary levels (mg/kg) of: |
||||
0 |
75 |
300 |
1200 |
4800 |
|||
Males |
|||||||
F0 |
|
No./group… |
9 |
9 |
9 |
10 |
10 |
Body weight (g) |
|
422 |
398 |
383 |
391 |
362 |
|
Adrenals |
|
0.011 |
0.011 |
0.011 |
0.011 |
0.012 |
|
Thyroid |
|
0.0060 |
0.0057 |
0.0056 |
0.0060 |
0.0060 |
|
Pituitary |
|
0.0029 |
0.0029 |
0.0029 |
0.0030 |
0.0033 |
|
Testes |
|
0.680 |
0.745 |
0.776** |
0.744 |
0.712 |
|
Prostate |
|
0.119 |
0.130 |
0.121 |
0.135 |
0.134 |
|
F1 |
|
No./group… |
10 |
10 |
10 |
10 |
- |
Body weight (g) |
|
409 |
391 |
388 |
395 |
- |
|
Adrenals |
|
0.010 |
0.010 |
0.011 |
0.012 |
- |
|
Thyroid |
|
0.0063 |
0.0064 |
0.0060 |
0.0067 |
- |
|
Pituitary |
|
0.0026 |
0.0026 |
0.0027 |
0.0028 |
- |
|
Testes |
|
0.771 |
0.759 |
0.769 |
0.763 |
- |
|
Prostate |
|
0.077 |
0.093 |
0.093 |
0.102* |
- |
|
F2 |
|
No./group… |
10 |
10 |
10 |
10 |
- |
Body weight (g) |
|
438 |
373** |
397** |
378** |
- |
|
Adrenals |
|
0.010 |
0.010 |
0.009 |
0.010 |
- |
|
Thyroid |
|
0.0076 |
0.0074 |
0.0079 |
0.0081 |
- |
|
Pituitary |
|
0.0032 |
0.0031 |
0.0027** |
0.0029 |
- |
|
Testes |
|
0.787 |
0.821 |
0.679 |
0.793 |
- |
|
Prostate |
|
0.103 |
0.102 |
0.109 |
0.104 |
- |
|
Females |
|||||||
F0 |
|
No./group… |
7 |
11 |
9 |
12 |
11 |
Body weight (g) |
|
254 |
256 |
249 |
243 |
249 |
|
Adrenals |
|
0.020 |
0.019 |
0.019 |
0.017* |
0.017** |
|
Thyroid |
|
0.0062 |
0.0066 |
0.0066 |
0.0073 |
0.0073 |
|
Pituitary |
|
0.0056 |
0.0055 |
0.0052 |
0.0052 |
0.0046 |
|
Ovaries |
|
0.022 |
0.021 |
0.022 |
0.025 |
0.024 |
|
Uterus |
|
0.171 |
0.166 |
0.180 |
0.150 |
0.143 |
|
F1 |
|
No./group… |
19 |
15 |
14 |
16 |
- |
Body weight (g) |
|
244 |
254 |
252 |
241 |
- |
|
Adrenals |
|
0.018 |
0.018 |
0.017 |
0.017 |
- |
|
Thyroid |
|
0.0073 |
0.0070 |
0.0074 |
0.0083 |
- |
|
Pituitary |
|
0.0047 |
0.0052 |
0.0049 |
0.0053* |
- |
|
Ovaries |
|
0.026 |
0.029 |
0.027 |
0.027 |
- |
|
Uterus |
|
0.167 |
0.159 |
0.150 |
0.140* |
- |
|
F2 |
|
No./group… |
10 |
10 |
10 |
10 |
- |
Body weight (g) |
|
267 |
244 |
259 |
241** |
- |
|
Adrenals |
|
0.019 |
0.018 |
0.017 |
0.018 |
- |
|
Thyroid |
|
0.0096 |
0.0083 |
0.0094 |
0.0103 |
- |
|
Pituitary |
|
0.0053 |
0.0048 |
0.0050 |
0.0056 |
- |
|
Ovaries |
|
0.027 |
0.024 |
0.027 |
0.027 |
- |
|
Uterus |
|
0.188 |
0.160 |
0.179 |
0.164 |
- |
+All organ weights are expressed in g/100 g body weight.
Asterisks indicate means differing significantly from that of the corresponding control group: *-0.01 ≤ p < 0.05; **-0.001 ≤ p < 0.01.
Table 3. Bromide concentration (corrected for control values) in plasma, tissues and 20 -day foetuses of female rats fed sodium bromide at 75 -4800 mg/kg diet for 7 months.
Dietary concentration of NaBr (mg/kg) |
Maternal levels of Br- |
Br- in foetal kidneys (mmol/kg) |
||
Plasma (mmol/litre) |
Placenta (mmol/kg) |
Kidneys (mmol/kg) |
||
75 |
0.5 ± 0.1 |
0.4 ± 0.1 |
0.3 ± 0.1 |
0.3 ± 0.1 |
300 |
2.2 ± 0.1 |
1.4 ± 0.1 |
1.4 ± 0.3 |
0.9 ± 0.1 |
1200 |
7.8 ± 0.9 |
6.3 ± 1.5 |
4.4 ± 1.1 |
3.2 ± 0.8 |
4800 |
27.6 ± 2.8 |
16.7 ± 1.5 |
15.3 ± 1.4 |
11.0 ± 0.6 |
Values are means ±SD for groups of seven animals.
Effect levels:
The effect levels were reported as Concentration of the substance in feed (mg/kg diet). In order to express the dose levels as mg/kg Body Weight Per Day, a conversion factor of 0.1 for young rats and 0.05 for older rats were used (in accordance with the OECD Environment, Health and Safety Publications Series on Testing and Assessment No.51, Paris, 2006).
Applicant's summary and conclusion
- Conclusions:
- The NOAEL for reproductive and developmental toxicity was determined to be 1200 mg/kg diet (equivalent to 120 and 60 mg/kg bw/d for young and older rats, respectively).
- Executive summary:
A three-generation reproduction study was performed with the test substance sodium bromide on Wistar rats at dietary concentrations of 0, 75, 300, 1200, 4800 and 19,200 mg NaBr/kg diet. For the performance of the experiment, male rats of proven fertility were mated with females for the first time at the age of 4 months. In three successive generations, at least two litters per female rat were raised. Besides, in the first generation a third litter was raised for the investigation of the transplacental transport of bromide and an additional litter was bred with parent animals of the highest dose group which were changed to the control diet in order to investigate the reversibility of the observed effects. Fertility index, viability and lactation indices were evaluated for each generation. Haematological examinations were made and the thyroid function was evaluated. Body- and organ-weights were also determined. The bromide concentration determination in foetal kidneys of the third litter of the first generation showed that foetuses in utero were indeed exposed to bromide. Body- and organ-weight determinations did not reveal a clear pattern of dose-related effects in the successive generations. The fertility was found to be nil in the 19,200 -mg group and was markedly reduced in the 4800 -mg group. Nevertheless, the decrease in fertility appeared to be reversible upon bromide withdrawal. In the 4800 -mg group also the viability of the offspring was lower than in the other groups. Macroscopic examination of all pups provided no evidence of anomalies. Besides the effects on fertility and viability, the most prominent effect observed in the present study was a decrease in thyroid hormone (T4) concentration in the serum of the parent animals of the P -generation. This finding is indicative of an inhibitory action of bromide on the synthesis of thyroid hormones. On the basis of the effect of sodium bromide on the thyroid function, a no-effect level of 300 mg/kg diet was determined (equivalent to 30 and 15 mg/kg bw/d for young and older rats, respectively). On the basis on the fertility and viability indices, the NOAEL for reproductive and developmental toxicity was determined to be 1200 mg/kg diet (equivalent to 120 and 60 mg/kg bw/d for young and older rats, respectively).
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