Potassium carbonate

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vivo

Type of information:

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

Adequacy of study:

key study

Justification for type of information:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read-across hypothesis is based on transformation of the target and source substances to common compounds (scenario 1 of the Read-Across Assessment Framework (RAAF), ECHA, March 2017 - transformation to common compounds). The target substance potassium carbonate as well as the source substances potassium hydrogencarbonate and potassium chloride dissociate in aqueous media to potassium and the respective anion.

For further details, please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
Please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

3. ANALOGUE APPROACH JUSTIFICATION
Please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

4. DATA MATRIX
Please refer to the Justification for Read-Across attached in Iuclid Chapter 13.

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across: supporting information

Principles of method if other than guideline:

synopsis on toxicokinetics of potassium and carbonate

Conclusions:

Interpretation of results: no bioaccumulation potential based on study results
In conclusion, the ions K+ or CO32- resulting from the ionisation (dissociation) of K2CO3 will not influence the natural K+ or CO32- level in the body due to natural regulation mechanisms.

Executive summary:

After ingestion, potassium carbonate rapidly dissociates in the gastric juice to yield carbonate ions (CO₃^2-) and potassium ions (K⁺), at this stage, the alkalinity is neutralized by the stomach acid. For this reason undissociated potassium carbonate is not expected to be systemically available in the body under normal handling and use conditions.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

As reported in ECHA TGD R.7c., it is generally thought that ionized substances do not readily diffuse across biological membranes, for cationic trace elements an estimate of < 1% is given. Thus, the dermal as well as the inhalative absorption of potassium carbonate is expected to be low due to its ionic structure. In addition, the ions K⁺ and CO₃^2- resulting from the ionisation (dissociation) of K₂CO₃ will not influence the natural K⁺ or CO₃^2- level in the body due to natural regulation mechanisms as discussed below.

After ingestion, potassium carbonate rapidly dissociates in the gastric juice to yield carbonate ions (CO₃ ^2-) and potassium ions (K⁺), at this stage, the alkalinity is neutralized by the stomach acid. For this reason undissociated potassium carbonate is not expected to be systemically available in the body under normal handling and use conditions and the systemic action of potassium carbonate must be discussed for its dissociation products, carbonate and potassium ions, separately. All ions involved, are naturally occurring essential ions in human beings effectively processed and regulated in the body by natural physiological mechanism. Their metabolism and mechanisms of action are well reviewed in standard textbooks on pharmacology and physiology. Synopses on both ions have been elaborated within the OECD work on investigation of high production volume chemicals. The description given in the following are excerpts of the OECD SIDS Initial Assessment Reports on Bicarbonate special and Potassium Chloride. However, comparable information is also given in the OECD SIDS Initial Assessment Reports on Sodium carbonate, Sodium bicarbonate, Ammonium hydrogencarbonate, Potassium hydroxide or Potassium methanolate.

Carbonate and hydrogencarbonate

The major extra-cellular buffer in the blood and the interstitial fluid of vertebrates is the bicarbonate buffer system, described by the following equation:

H₂O + CO₂ <=> H₂CO₃<=> H⁺ + HCO₃^-

Carbon dioxide from the tissues diffuses rapidly into red blood cells, where it is hydrated with water to form carbonic acid. This reaction is accelerated by carbonic anhydrase, an enzyme present in high concentrations in red blood cells. The carbonic acid formed dissociates into bicarbonate and hydrogen ions. Most of the bicarbonate ions diffuse into the plasma. Since the ratio of H₂CO₃ to dissolved CO₂ is constant at equilibrium, pH may be expressed in terms of bicarbonate ion concentration and partial pressure of CO₂ by means of Henderson-Hasselbach equation:

            pH = pK + log [HCO₃^-]/αP_CO2

Human blood plasma has normally a pH of 7.40. Should the pH fall below 7.0 or rise above 7.8, irreversible damage may occur. Compensatory mechanisms for acid-base disturbances function altering the ratio of [HCO₃^-] to PCO₂, and returning the pH of the blood to normal. Thus, metabolic acidosis may be compensated for by hyper-ventilation and increased renal absorption of HCO₃^-. Metabolic alkalosis may be compensated for by hypo-ventilation and the excess of excretion of HCO₃^- in urine. Renal mechanisms are usually sufficient to restore the acid-balance.

Potassium

Potassium is an essential constituent and one of the most abundant ions in all animal species. In adult humans, the total body potassium content is approximately 3.5 mol (135 g). 98 % of this is located intracellular (150 mmol/l), the extracellular potassium concentration is approximately 4 mmol/l.

About 90 % of the ingested dose of potassium is absorbed by passive diffusion in the membrane of the upper intestine. Potassium is distributed to all tissues where it is the principal intracellular cation. Insulin, acid-base status, aldosterone, and adrenergic activity regulate cellular uptake of potassium.

The majority of ingested potassium is excreted in the urine via glomerular filtration. The distal tubules are able to secrete as well as reabsorb potassium, so they are able to produce a net secretion of potassium to achieve homeostasis in the face of a potassium load due to abnormally high levels of ingested potassium. About 15 % of the total amount of potassium excreted is found in faeces. Excretion and retention of potassium is mainly regulated by the main adrenal cortical hormones. Normal homeostatic mechanisms controlling the serum potassium levels allow a wide range of dietary intake. The renal excretory mechanism is designed for efficient removal of excess potassium, rather for its conservation during deficiency. Even with no intake of potassium, humans lose a minimum of 585-1170 mg potassium per day. However, the distribution of potassium between the intracellular and the extracellular fluids can markedly affect the serum potassium level without a change in total body potassium.

K⁺ is the principal cation mediating the osmotic balance of the body fluids. In animals, the maintenance of normal cell volume and pressure depends on Na⁺ and K⁺ pumping. The K⁺/Na⁺ separation has allowed for evolution of reversible transmembrane electrical potentials essential for nerve and muscle action in animals, and potassium is important in transmission of nerve impulses to the muscle fibers. Potassium transport through the hydrophobic interior of a membrane can be facilitated by a number of natural compounds that form lipid-soluble alkali metal cation complexes. Potassium serves the critical role as counterion for various carboxylates, phosphates and sulphates, and stabilizes macromolecular structures. Potassium is also important in the regulation of the acid-base balance of the body. Potassium is the principal base in tissues of blood cells.

In conclusion, the ions K⁺ and CO₃^2- resulting from the ionisation (dissociation) of K₂CO₃ will not influence the natural K⁺ or CO₃^2- level in the body due to natural regulation mechanisms.

Discussion on absorption rate:

As reported in ECHA TGD R.7c., it is generally thought that ionized substances do not readily diffuse across biological membranes, for cationic trace elements an estimate of < 1% is given. Thus, the dermal as well as the inhalative absorption of potassium carbonate is expected to be low due to its ionic structure. In addition, the ions K⁺ and CO₃^2- resulting from the ionisation (dissociation) of K₂CO₃ will not influence the natural K⁺or CO₃^2- level in the body due to natural regulation mechanisms.