Potassium hydrogencarbonate

Toxicity to reproduction

Administrative data

Endpoint:

extended one-generation reproductive toxicity - basic test design (Cohorts 1A, and 1B without extension)

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

Potassium and (hydrogen)carbonate are essential constituents and two of the most abundant ions in all animal species. In adult humans, the total body potassium is approx. 3.5 mol (135 g). 98 % of this is located intracellular (150 mmol/l), the extracellular potassium concentration is approx. 4 mmol/l.

The metabolism and mechanisms of action of potassium and (hydrogen)carbonate are well reviewed in standard textbooks on pharmacology and physiology.

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 glomelural 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 K, rather for its conservation during deficiency. Even with no intake of K, humans lose a minimum of 585-1170 mg K 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 both potassium and chloride are 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 (OECD SIDS, 2001).

The bicarbonate buffer system described by the following equation:
H2O + CO2 <=> H2CO3 <=> H+ + (HCO3)-
is the major extracellular buffer in the blood and the interstitial fluid of vertebrates. The blood plasma of man normally has 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 to alter the ratio of (HCO3)- to PCO2, returning the pH of the blood to normal. Thus, metabolic acidosis may be compensated for by hyperventilation and increased renal absorption of (HCO3)-. Metabolic alkalosis may be compensated for by hypoventilation and the excess of (HCO3)- in the urine. Renal mechanisms are usually sufficient to restore the acid-base balance (OECD SIDS, 2002).

No fertility study has been localised for potassium hydrogencarbonate or related substances. However, the maximum plasma concentration of potassium and (hydrogen)carbonate is efficiently and tightly regulated by renal elimination. A significant increase in the potassium concentration in the extracellular fluid will only occur after high potassium intake or in patients with severely reduced kidney function.

No effects of exposure potassium hydrogencarbonate on gonadal function can be expected if the plasma concentrations are within the normal range, as neither potassium nor hydrogencarbonate accumulates in the body. Based on the extensive amount of knowledge on regulation and effects of potassium and (hydrogen)carbonate in the human body, no further testing of fertility is required.

References
OECD SIDS, 2001. Potassium chloride. SIDS Initial Assessment Report for 13th SIAM. UNEP Publications.

OECD SIDS, 2002. Sodium bicarbonate. SIDS Initial Assessment Report for 15th SIAM. UNEP Publications.

Results and discussion

Overall reproductive toxicity

Reproductive effects observed:

not specified