Dipotassium oxide

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Objective of study:

absorption

distribution

excretion

toxicokinetics

Principles of method if other than guideline:

citation of a summarizing review

GLP compliance:

not specified

Radiolabelling:

not specified

Preliminary studies:

Total body potassium is estimated to be approximately 135 g in a 70 kg adult man. Extracellular potassium (circa 2% of body pool) is important for regulation the membrane potential of the cells and thus for nerve and mscle function, blood pressure regulation, ...
Potassium also participates in the acid-base balance. 98% of the potassium in the body is found in the cells, where it is the main intracellular cation.
The absorption of potassium is effective and about 85-90% of dietary potassium is absorbed from the gut. The potassium balance is primarily regulated by renal excretion in urine.
The concentration of potassium in plasma is tightly regulated within a narrow range of about 3.5 to 5 mmol/L. The body is able to accommodate a high intake of potassium, without any substantial change in plasma concentration by synchronized alterations in both renal and extra-renal handling, with potassium either being excreted in the urine or taken up into cells.

Conclusions:

Interpretation of results : no bioaccumulation potential based on study results
Potassium is an essential nutrient involved in fluid, acid and electrolyte balance and is required for normal cellular function. Dietary deficiency of potassium is very uncommon due to the widespread occurrence of potassium in foods. Available evidence suggests that potassium can modulate blood
pressure and increasing dietary potassium intake is associated with lower blood pressure. However, the available data are insufficient to establish a safe upper intake level for potassium. Based on estimates of current potassium intakes in European countries, the risk of adverse effects from potassium intake from food sources is considered to be low for the generally healthy population (children and adults). The average intake in adults from the diet is 3-4 g and the intake generally does not exceed 5-6 g per day. Total body potassium is estimated to be approximately 135 g in a 70 kg adult man.
Extracellular potassium (circa 2% of body pool) is important for regulation the membrane potential of the cells and thus for nerve and mscle function, blood pressure regulation, ...
Potassium also participates in the acid-base balance. 98% of the potassium in the body is found in the cells, where it is the main intracellular cation.
The absorption of potassium is effective and about 85-90% of dietary potassium is absorbed from the gut. The potassium balance is primarily regulated by renal excretion in urine.
The concentration of potassium in plasma is tightly regulated within a narrow range of about 3.5 to 5 mmol/L. The body is able to accommodate a high intake of potassium, without any substantial change in plasma concentration by synchronized alterations in both renal and extra-renal handling, with potassium either being excreted in the urine or taken up into cells.
Daily intakes of potassium from the habitual diet generally do not exceed 5-6 g/day and has not been associated with any negative effects in healthy individuals. Elderly people may be more vulnerable to potassium toxicity due to reduced physiological reserve in renal function.

Reference 2

Endpoint:

dermal absorption in vivo

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

QSAR prediction:US EPA accepted QSAR method for chemicals properties assessment.

Qualifier:

no guideline required

Principles of method if other than guideline:

Using the DERMWIN v2.01 QSAR model

GLP compliance:

no

Remarks:

not applicable to QSAR models

Radiolabelling:

no

Species:

other: QSAR model,

Strain:

other: QSAR model,

Sex:

not specified

Type of coverage:

other: QSAR model

Vehicle:

other: QSAR model

Duration of exposure:

not applicable to QSAR models

Doses:

not applicable to QSAR models

No. of animals per group:

not applicable to QSAR models

Control animals:

no

Details on study design:

not applicable to QSAR models

Details on in vitro test system (if applicable):

not applicable to QSAR models

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

A QSAR model predicts that the permeability of Dipotassium oxide to human skin is quite low. The permeability coefficient was determined to be
0.000247 mg/cm2, which is around 1% of the skin penetration rate.
Predicted dermally absorbed coefficient was determined to be Kp (est)=1.96e-007 cm/hr.

A QSAR model predicts that the permeability of Dipotassium oxide to human skin is quite low. The permeability coefficient was determined to be 0.000247 mg/cm2, which is around 1% of the skin penetration rate.

Predicted dermally absorbed coefficient was determined to be Kp (est)=1.96e-007 cm/hr.

Conclusions:

A QSAR model predicts that the permeability of Dipotassium oxide to human skin is quite low. The permeability coefficient was determined to be
0.000247 mg/cm2, which is around 1% of the skin penetration rate.
Predicted dermally absorbed coefficient was determined to be Kp (est)=1.96e-007 cm/hr.

Executive summary:

A QSAR model predicts that the permeability of Dipotassium oxide to human skin is quite low. The permeability coefficient was determined to be 0.000247 mg/cm2, which is around 1% of the skin penetration rate.

Predicted dermally absorbed coefficient was determined to be Kp (est)=1.96e-007 cm/hr.

Description of key information

Potassium oxide has not bioaccumulation potential.
Potassium is essential constituent and one 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.
Oxygen is the most abundant chemical element by mass in the Earth's biosphere, air, sea and land. Oxygen is the third most abundant chemical element in the universe, after hydrogen and helium
Both K+ and O- ions are normal constituents of the body fluids. K+ plays an essential role in the human physiology but starts to be toxic at levels exceeding 200 – 250 mg/l. Its concentration in the blood is regulated principally by renal excretion/reabsorption and controlled by an efficient feedback auto-regulation system. An excessive pH of the blood is prevented by the bicarbonate buffer system, respiration and renal compensation mechanisms.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Absorption rate - dermal (%):

1

Additional information

TOXICOKINETICS, METABOLISM, MECHANISMS OF ACTION

Potassium oxide is produced from the reaction of oxygen and potassium; this reaction affords potassium oxide, K2O.

Oxygen is the most abundant chemical element by mass in the Earth's biosphere, air, sea and land. Oxygen is the third most abundant chemical element in the universe, after hydrogen and helium

Potassium is essential constituent and one 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 is well reviewed in standard textbooks on pharmacology and physiology.

Metabolism, biotransformation and kinetics:

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.

Mechanisms of action:

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 hydrofobic 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.

Conclusion

Both K+ and O- ions are normal constituents of the body fluids. K+ plays an essential role in the human physiology but starts to be toxic at levels exceeding 200 – 250 mg/l. Its concentration in the blood is regulated principally by renal excretion/reabsorption and controlled by an efficient feedback auto-regulation system. An excessive pH of the blood is prevented by the bicarbonate buffer system, respiration and renal compensation mechanisms.

Potassium oxide has not bioaccumulation potential.

Potassium is essential constituent and one 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.

Oxygen is the most abundant chemical element by mass in the Earth's biosphere, air, sea and land. Oxygen is the third most abundant chemical element in the universe, after hydrogen and helium

Both K+ and O- ions are normal constituents of the body fluids. K+ plays an essential role in the human physiology but starts to be toxic at levels exceeding 200 – 250 mg/l. Its concentration in the blood is regulated principally by renal excretion/reabsorption and controlled by an efficient feedback auto-regulation system. An excessive pH of the blood is prevented by the bicarbonate buffer system, respiration and renal compensation mechanisms.