Registration Dossier

Toxicological information

Basic toxicokinetics

Currently viewing:

Administrative data

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.

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

Constituent 1
Chemical structure
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
Test material form:
solid
Details on test material:
Molecular formula: NH4H2PO4
No further details available

Radiolabelling:
no

Results and discussion

Main ADME results
Type:
absorption
Results:
For oral, dermal and inhalation exposure, 100, 10 and 100% absorption, respectively, are used for risk assessment.

Toxicokinetic / pharmacokinetic studies

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.

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. 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.

Applicant's summary and conclusion