Reaction mass of Ammonium dihydrogenorthophosphate and diammonium hydrogenorthophosphate.

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: expert statement

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Based on the current knowledge the statement has been written.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Objective of study:

absorption

Principles of method if other than guideline:

no guideline as it is an expert statement

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Monoammonium phosphate (MAP)

IUPAC Name:

Monoammonium phosphate (MAP)

Constituent 2

Reference substance name:

Ammonium dihydrogenorthophosphate

EC Number:

231-764-5

EC Name:

Ammonium dihydrogenorthophosphate

Cas Number:

7722-76-1

Molecular formula:

H3N.H3O4P

IUPAC Name:

ammonium dihydrogen phosphate

Constituent 3

Reference substance name:

DIammonium phosphate (DAP)

IUPAC Name:

DIammonium phosphate (DAP)

Constituent 4

Reference substance name:

Diammonium hydrogenorthophosphate

EC Number:

231-987-8

EC Name:

Diammonium hydrogenorthophosphate

Cas Number:

7783-28-0

Molecular formula:

H9N2O4P

IUPAC Name:

diammonium hydrogen phosphate

Constituent 5

Reference substance name:

triammonium dihydrogen phosphate hydrogen phosphate

EC Number:

913-888-8

Molecular formula:

H3N.H3O4P H9N2O4P

IUPAC Name:

triammonium dihydrogen phosphate hydrogen phosphate

Radiolabelling:

no

Results and discussion

Main ADME results

Type:

absorption

Results:

Based on low MW and high water solubility: 100% oral absorption is expected. For dermal exposure 10% absorption is taken, due to the high water solubility and ionisation of the two components.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Based on low MW and high water solubility oral absorption is expected. Therefore, 100% absorption is taken for oral exposure.
since the vapour pressure of the reaction mass is assimilated to the vapour pressure of water, inhalation exposure to the liquid form of the
reaction mass is not expected.
For dermal exposure 10% absorption is taken, due to the high water solubility and ionisation of the two components.

Any other information on results incl. tables

In general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract after oral administration. MAP and DAP will be dissociated in its ions in water. (Di)hydrogenphosphate is in equilibrium with phosphate. The transport of phosphate from the lumen is an active, energy-dependent process. In general, about two thirds of the ingested phosphate is absorbed from the gastrointestinal tract in adults. After ingestion, ammonium ions can be absorbed by diffusion of the unionized ammonia or by active transport of ammonium ion. After intestinal absorption, ammonium ions are converted to urea by the liver, and subsequently excreted in urine. The relatively small molecular weights (below 200) and the high water solubility (>10 g/L) indicate that uptake of MAP and DAP can also take place through aqueous pores. It is therefore likely that MAP and DAP will be absorbed from the gastro-intestinal tract. Oral absorption of the liquid form of the reaction mass of MAP and DAP is set at 100%.

 

Once absorbed, distribution of Ammonium dihydrogenorthophosphate and Diammonium hydrogenorthophosphate throughout the body is expected based on their relatively low molecular weight, and no accumulation in the body is anticipated based on their hydrophilic character. Ammonium dihydrogenorthophosphate and Diammonium hydrogenorthophosphate have characteristics favourable for fast urinary excretion: low molecular weight (below 200), good water solubility, and ionization of the molecules at the pH of urine. Based on its hydrophilic character, extracellular concentration is also expected to be higher than intracellular concentration.The rate at which these highly water-soluble molecules distribute may be limited by the rate at which they cross cell membranes and access of these substances to the central nervous system (CNS) or testes is likely to be restricted by the blood-brain and blood-testes barriers.

 

Since the vapour pressure of the liquid form of the reaction mass of Ammonium dihydrogenorthophosphate and Diammonium hydrogenorthophosphate is low (assimilated to the vapour pressure of water), inhalation exposure to the liquid form of the reaction mass is not expected.

Ammonium dihydrogenorthophosphate and Diammonium hydrogenorthophosphate ionize as soon as they dissolve and having water solubility above 10 g/L. Moreover, these substances may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, 10% dermal absorption of the reaction mass is proposed.