Ammonium nitrate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

Remarks:

expert statement

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:

Ammonium nitrate

EC Number:

229-347-8

EC Name:

Ammonium nitrate

Cas Number:

6484-52-2

Molecular formula:

H3N.HNO3

IUPAC Name:

ammonium nitrate

Test material form:

solid

Remarks:

granules or crystals

Details on test material:

No further details provided.

Radiolabelling:

no

Results and discussion

Main ADME results

Type:

absorption

Results:

50% absorption is taken for oral, dermal and inhalation exposure.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

Based on low MW, high water solubility, assumed low logPow high absorption is expected. However, the ion formation of the substance inmediately when in contact with a fluid decreases the absorption. The guidance has also been taken into consideration. Therefore, 50% absorption is taken for oral, dermal and inhalation exposure.

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. The low molecular weight (MW= 80.043) and high water solubility (>10 g/L) of ammonium nitrate are favourable for uptake from the gastro-intestinal tract. This combination of low molecular weight and high water solubility is indicative for possible passage of the substance through aqueous pores (1). On the other hand, ammonium nitrate being a water soluble salt, will dissociate into ammonium and the nitrate/nitrite anion, which will impair the passage of the gastrointestinal wall (1). Although a partition coefficient cannot be determined for ammonium nitrate, it is considered to be, due to its chemical properties, and not favourable for uptake from the gastrointestinal tract. For risk assesment purposes, the oral absorption is set at 50%. The results of the toxicity studies do not provide reason to deviate from this proposed oral absorption.

Once absorbed, widely distribution of ammonium nitrate, by means its dissociation products, is expected based on its low molecular weight. Nitrate and nitrite are naturally occurring inorganic ions which are part of the nitogen cycle. The ammonium cation is an integral component of normal human metabolic processes and is metabolized (to urea) in the human body. Excretion will be mainly via urine (3).

 

The negligible vapour pressure of ammonium nitrate at room temperature indicates that the substance is not available for inhalation as a vapour. The particle size (no particles below 100μm) indicates that there are no inhalable particles present. Based on these properties, no respiratory exposure and hence no inhalation absorption is to be expected. If, however, during the use of the product particles between 100 and 10μm are generated, deposition of these particles in the nasopharyngeal region will take place. Subsequently, these particles will be coughed or sneezed out of the body or swallowed. Particles below 10μm might reach the tracheobronchial or pulmonary regions. The high water solubility of ammonium nitrate (>10 g/L) indicates that the substance will dissolve in the mucus lining of the respiratory tract and subsequently be absorbed through aqueous pores (taking the molecular weight of 80.043 into account). The assumed low partition coefficient of ammonium nitrate is, however, indicative for low potential of absorption directly across the respiratory tract epithelium. Overall, it is concluded that when ammonium nitrate is inhaled (particles <10μm only), absorption of ammonium nitrate is to be expected, and for risk assessment purposes the inhalation absorption for ammonium nitrate is set at 50%.

 

Ammonium nitrate being a very well water soluble substance has the potential to be dermal absorbed as the surface moisture of the skin will not limit the availablility. The molecular weight and high water solubility of ammonium nitrate are favourable for dermal uptake. Although a partition coefficient cannot be determined for ammonium nitrate, it is considered to be low. The criteria for reduced dermal absorption as given in the TGD (2) (MW>500log Pow is smaller than -1 or higher than 4)not,therefore 100% dermal absorption of ammonium nitrate should be considered for risk assessment purposes. Since it is assumed that dermal absorption will not exceed oral absorption, the oral absorption of 50% may be considered as a more realistic value for dermal absorption.