Potassium 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 ammonium 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

Potassium 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 potassium 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.

 

Further data on the potassium 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;

Potassium is a very significant body mineral, important to both cellular and electrical function being crucial to heart function and playing a key role in skeletal and smooth muscle contraction.

Potassium is an essential macromineral in human nutrition; it is the major cation inside animal cells, and it is thus important in maintaining fluid and electrolyte balance in the body. Whilst sodium is the major cation in blood plasma at a reference range of about 145 mmol/L (3.345 g), potassium makes up most of the cell fluid cations at about 150 mmol/L (4.8 g). Plasma is filtered through the glomerulus of the kidneys at about 180 liters per day. Thus 602 g of sodium and 33 g of potassium are filtered each day. All but the 1–10 g of sodium and the 1–4 g of potassium likely to be in the diet must be reabsorbed. Potassium must be reabsorbed in such a way as to keep serum concentration as close as possible to 4.8 mmol/L (about 0.190 g/L). Potassium must sometimes be conserved, but, as the amount of potassium in blood plasma is very small and the pool of potassium in the cells is about thirty times as large, the situation is not critical for potassium in comparison to sodium. Since potassium is moved passively in counter flow to sodium in response to an apparent Donnan equilibrium, urine can never sink below the concentration of potassium in serum except sometimes by actively excreting water at the end of the processing. Potassium is secreted twice and reabsorbed three times before the urine reaches the collecting tubules. At that point, it usually has about the same potassium concentration as plasma. At the end of the processing, potassium is secreted one more time if the serum levels are too high.

If potassium were removed from the diet, there would remain a minimum obligatory kidney excretion of about 200 mg per day when the serum declines to 3.0–3.5 mmol/L in about one week, and can never be cut off completely, the end result being hypokalemia and possibly death.

Further, 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 ammonium bromide. Although ammonium 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.

Discussion on bioaccumulation potential result:

Ammonium 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 ammonium 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.

 

Information on metabolism and toxicokinetics of the ammonium moiety of ammonium bromide is limited. Further data on the ammonium moiety is however not considered necessary due to the chemical simplicity. The fate of ammonium in the organism is considered predictable (incorporation into urea cycle and conversion to urea) due to its physiological role in the supply of nitrogen. Further, the toxicity seems to be triggered by the bromide ion rather than by the ammonium ion as shown in repeated dose toxicity studies (no systemic toxicity seen in the investigation of ammonium sulphate; 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.

 

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 ammonium bromide. Although ammonium 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:

No guideline study is available. The distribution of bromide is like the chloride ion: bromide is mainly distributed in the extracellular fluid and it passes the blood brain barrier. In rats, radioactive bromide was found in red blood cells, cerebrospinal fluid, thyroid gland, blood vessel walls, cartilage, tendons, dentine, kidneys, urinary bladder, stomach and the eye. No significant amounts of bromide observed in fat or proteins of blood. Bromide can cross the placenta to the foetus more readily than it can be eliminated by the foetus back to the maternal blood. Thus, there is a potential for accumulation in the foetus, and there have been human cases of congenital bromism. In foetuses, most radioactive bromide was found in cartilage. Bromide can also pass into breast milk.

 

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).

 

Metabolism:

No guideline study is available. Bromide is not subjected to hepatic metabolism and is not bound to plasma proteins (this stated in publications from the open literature).

Discussion on absorption rate:

Ammonium 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 ammonium bromide.

No dermal absorption study is available with ammonium bromide. Although ammonium 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%).