Sodium bromide

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
The oral bioavailability of bromide  is reported to be at least 75% with absorption completed within a few hours. Dermal absorption of the bromide anion is expected to be low (< 1%).
The distribution of bromide is like the chloride ion: bromide is mainly distributed in the extracellular fluid and it passes the blood brain barrier and across the placenta to the foetus.
Excretion of bromide is mainly via the kidneys, where the bromide competes with chloride for tubular reabsorption. Other routes of excretion, such as sweat, saliva and faeces are quite minor. The plasma half-life is approximately 3 days in rats, 12 days in humans and 15-46 days in dogs. The half-life is dependent on chloride intake.
Bromide is not subjected to hepatic metabolism and is not bound to plasma proteins
Short description of key information on absorption rate: 
Although sodium bromide is a small molecule, it dissociates in water into ions and is not expected to easily penetrate the skin due to its electric charge. Further on data from the open literature indicate low dermal absorption of the bromide ion (<1%).

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - dermal (%):

1

Additional information

Sodium bromide is an inorganic salt that dissociates to its composite ions in aqueous solutions at environmental pH and temperature. Comparison of the available data on the various bromide salts have shown that the bromide ion is the relevant ion for determination of the toxicological profile with simple cations such as potassium, sodium or ammonium, that are ubiquitous in nature, having little or no influence on the bromide ion properties. It is therefore justified to read-across data from other inorganic bromide salts to sodium bromide.

Studies and investigations are performed with inorganic bromide salts on the kinetics and metabolism as well as on the dermal penetration following administration to rodents, dogs and human volunteers. The determination of the distribution pattern of the bromide ion in organs is limited. However, based on the weight of evidence from all available studies, the toxicokinetics of the bromide ion is considered to be sufficiently characterised in the investigations performed.

Sodium bromide

The toxicokinetics of sodium bromide was investigated in studies from published literature.

Absorption: Sodium bromide is completely absorbed orally (96%) in humans and is significantly absorbed by inhalation (aerosols) in guinea pigs. No data on dermal and inhalation absorption are available. Dermal absorption of sodium bromide is expected to be low. For risk assessment purposes oral and inhalation absorption is assumed to be 100%.

Distribution: Sodium bromide is rapidly distributed through the extracellular water. Bromide can enter the brain and cross the placenta.

Metabolism: Sodium bromide is not metabolised and competes with other halides in the body.

Excretion: Sodium bromide is excreted via the urine with a half-life of approximately 12 days in humans, depending on the chlorine (NaCl) content of the diet.

Sodium

Further data on the sodium moiety is however not considered necessary due to the chemical simplicity. The fate of potassium in the organism is considered predictable due to its physiological role in many metabolic processes;

Sodium is the major cation in blood plasma at a reference range of about 135 - 145 mmol/L (3.345 g). Plasma is filtered through the glomerulus of the kidneys at about 180 liters per day. Thus 602 g of sodium is filtered each day. All but the 1–10 g of sodium likely to be in the diet must be reabsorbed. The major source of sodium intake is as salt (sodium chloride, NaCl) in the diet.

Sodium regulates the total amount of water in the body and the transmission of sodium into and out of individual cells also plays a role in critical body functions. Many processes in the body, especially in the brain, nervous system, and muscles, require electrical signals for communication. The movement of sodium is critical in generation of these electrical signals.

Maintenance of membrane potential

Sodium and chloride areelectrolytesthat contribute to the maintenance of concentration and charge differences acrosscell membranes. Potassium is the principal positively charged ion (cation) inside of cells, while sodium is the principal cation in extracellular fluid. Potassium concentrations are about 30 times higher inside than outside cells, while sodium concentrations are more than ten times lower inside than outside cells. The concentration differences between potassium and sodium across cell membranes create an electrochemical gradient known as themembrane potential. A cell's membrane potential is maintained byionpumps in the cell membrane, especially the sodium, potassium-ATPase pumps. These pumps useATP(energy) to pump sodium out of the cell in exchange for potassium (diagram). Their activity has been estimated to account for 20%-40% of the resting energy expenditure in a typical adult. The large proportion of energy dedicated to maintaining sodium/potassium concentration gradients emphasizes the importance of this function in sustaining life. Tight control of cell membrane potential is critical for nerve impulse transmission, muscle contraction, and cardiac function.

Nutrient absorption and transport

Absorption of sodium in the small intestine plays an important role in the absorption of chloride,amino acids,glucose, and water. Similar mechanisms are involved in the reabsorption of these nutrients after they have been filtered from the blood by the kidneys.

Maintenance of blood volume and blood pressure

Because sodium is the primary determinant ofextracellular fluidvolume, including blood volume, a number of physiological mechanisms that regulate blood volume and blood pressure work by adjusting the body's sodium content. In the circulatory system, pressure receptors (baroreceptors) sense changes in blood pressure and send excitatory or inhibitory signals to the nervous system and/orendocrine glandsto affect sodium regulation by the kidneys. In general, sodium retention results in water retention and sodium loss results in water loss.

Therefore, too much or too little sodium can cause cells to malfunction, and extremes in the blood sodium levels (too much or too little) can be fatal:

Hyponatremia,defined as aserumsodium concentration of less than 136 mmol/liter, may result from increased fluid retention or increased sodium loss. Symptoms of hyponatremia include headache, nausea, vomiting, muscle cramps, fatigue, disorientation, and fainting. Complications of severe and rapidly developing hyponatremia may include cerebral edema (swelling of the brain), seizures, coma, and brain damage. Acute or severe hyponatremia may be fatal without prompt and appropriate medical treatment. 

Increased salt intake has been found to increase urinary excretion of calcium. Each 2.3 gram increment of sodium (5.8 grams of salt; NaCl salt) excreted by the kidneys draws about 24-40 milligrams (mg) of calcium into the urine which can lead to osteporosis. There is also strong evidence that higher sodium intake causes blood pressure to increase and reduced intake causes it to decrease.

Adequate intake (AI) for sodium

In 2004, the Food and Nutrition Board of the Institute of Medicine (USA) established an adequate intake level (AI) for sodium based on the amount needed to replace losses through sweat in moderately active people and to achieve a diet that provides sufficient amounts of other essential nutrients.

Adequate Intake (AI) for Sodium, with Estimated Sodium Chloride (Salt) Equivalence
Life Stage	Age	Males and Females Sodium (g/day)	Salt (g/day)
Infants	0-6 months	0.12	0.30
Infants	7-12 months	0.37	0.93
Children	1-3 years	1.0	2.5
Children	4-8 years	1.2	3.0
Children	9-13 years	1.5	3.8
Adolescents	14-18 years	1.5	3.8
Adults	19-50 years	1.5	3.8
Adults	51-70 years	1.3	3.3
Adults	71 years and older	1.2	3.0
Pregnancy	14-50 years	1.5	3.8
Breast-feeding	14-50 years	1.5	3.8

Bromide

The toxicity of bromide salts seems to be triggered by the bromide ion rather than by the cation associated with it as shown in repeated dose toxicity studies (a comparable toxicity profile demonstrated in the teratogenicity studies with ammonium bromide and sodium bromide).

 

The available information is mainly focused on the kinetics of the bromide ion since the bromide ion is considered to be the most relevant chemical species from the toxicological point of view.

The toxicokinetics of bromide was investigated in studies from published literature.

Absorption:

Oral

In humans the oral bioavailability of bromide taken on empty stomach is reported to be at least 75%. Absorption is rapid (completed within a few hours).

Dermal

No dermal absorption study is available with potassium bromide. Although potassium bromide is a small molecule, it dissociates in water into ions and is not expected to easily penetrate the skin due to its electric charge. Further on data from the open literature indicate low dermal absorption of the bromide ion (<1%).

Distribution:

Bromide is rapidly distributed through the extracellular water. Bromide can enter the brain and cross the placenta.

Metabolism:

Bromide is not metabolised and competes with other halides in the body.

Excretion:

Excretion of bromide is mainly via the kidneys, where the bromide competes with chloride for tubular reabsorption. Other routes of excretion, such as sweat, saliva and faeces are quite minor. The amount of bromide in excreta is not determined. The plasma half-life is approximately 3 days in rats, 12 days in humans and 15-46 days in dogs. Half-life dependents on chloride intake (decreased half-life with administration of surplus halide ions, e.g.chloride).

In conclusion, absorption of bromide via the oral route is approximately 100%. For the inhalation route also 100% is assumed. Dermal absorption is expected to be very low, as ions do not penetrate the skin easily. Bromide is not metabolised. Bromide is rapidly and evenly distributed through the body, with concentrations in the plasma be higher than in other tissues. Bromide can enter the brain and cross the placenta. Bromide is excreted slowly, with half-lives of 12 days in humans, 46 days in dogs and 198 hours in rats. The half-lives are greatly influenced by the NaCl content of the diet (inversely proportional). Bromide is mainly excreted via the urine. Bromide is also excreted in the milk. Bromide tends to compete with other ions in the body, e.g. for chloride excreted into the gastric environment.