Ammonium dihydrogenorthophosphate

Endpoint summary

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

basic toxicokinetics in vivo

Type of information:

not specified

Adequacy of study:

supporting study

Study period:

no data

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Remarks:

Secondary data source.

Details on absorption:

Phosphates are absorbed from the gastrointestinal tract as orthophosphate. The transport of phosphate from the lumen is an active, energy-dependent process, and there are factors that appear to modify the degree of its intestinal absorption. Vitamin D stimulates phosphate absorption, and this effect has been reported to precede the action of the vitamin on transport of calcium ion. In general, about two thirds of the ingested phosphate is absorbed from the gastrointestinal tract in adults. Absorbed phosphate is almost entirely excreted into the urine.

Reference 2

Endpoint:

basic toxicokinetics in vivo

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.

Objective of study:

absorption

Principles of method if other than guideline:

no guideline as it is an expert statement

GLP compliance:

no

Radiolabelling:

no

Type:

absorption

Results:

For oral, dermal and inhalation exposure, 100, 10 and 100% absorption, respectively, are used for risk assessment.

Details on absorption:

Based on low MW, high water solubility, assumed low logPow high oral absorption is expected. Therefore, 100% absorption is taken for oral and inhalation exposure. For dermal exposure 10% absorption is taken, due to the high water solubility, assumed low logPow and ionisation of the substance.

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. For risk assessment purposes oral absorption of MAP and DAP is set at 100%.

 

Once absorbed, distribution of MAP and DAP 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. MAP and DAP have characteristics favourable for fast urinary excretion: low molecular weight (below 300), good water solubility, and ionization of the molecules at the pH of urine.Based on its hydrophilic character, extracellularcentration 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.

 

Due to the low aerodynamic diameter of the substances it is expected that MAP and DAP will reach the nasopharyncheal region or subsequently the tracheobronchial or pulmonary region, although the vapour pressure of the substances itself is low. Asvery hydrophilic substances with low molecular weights,any MAP and DAP reaching the lungsmight be absorbed through aqueous pores or be retained in the mucus and transported out of the respiratory tract.Overall, although it is unlikely that MAP and DAP vapour will be available to a high extent after inhalation via the lungs, particles will be available after inhalation via the lungs due to the low aerodynamic diameter. For risk assessment purposes the inhalation absorption of MAP and DAP is set at 100%.

 

MAP and DAP ionize as soon as they dissolve and having water solubility above 10 g/l and the log P value below 0 may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, 10% dermal absorption of MAP and DAP is proposed for risk assessment purposes.

Description of key information

A toxicokinetic assessment was performed based on the available data of the substance. 

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

100

Absorption rate - dermal (%):

10

Absorption rate - inhalation (%):

100

Additional information

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 third 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. For risk assessment purposes oral absorption of MAP and DAP is set at 100%.

 

Once absorbed, distribution of MAP and DAP 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. MAP and DAP have characteristics favourable for fast urinary excretion: low molecular weight (below 300), 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.

 

Due to the low aerodynamic diameter of the substances it is expected that MAP and DAP will reach the nasopharyncheal region or subsequently the tracheobronchial or pulmonary region, although the vapour pressure of the substances itself is low. Asvery hydrophilic substances with low molecular weights,any MAP and DAP reaching the lungsmight be absorbed through aqueous pores or be retained in the mucus and transported out of the respiratory tract.Overall, although it is unlikely that MAP and DAP vapour will be available to a high extent after inhalation via the lungs, particles will be available after inhalation via the lungs due to the low aerodynamic diameter. For risk assessment purposes the inhalation absorption of MAP and DAP is set at 100%.

 

MAP and DAP ionize as soon as they dissolve and having water solubility above 10 g/l and the log P value below 0 may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, 10% dermal absorption of MAP and DAP is proposed for risk assessment purposes.