Registration Dossier

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

Constituent 1
Chemical structure
Reference substance name:
Magnesium sulphate
EC Number:
231-298-2
EC Name:
Magnesium sulphate
Cas Number:
7487-88-9
Molecular formula:
H2O4S.Mg
IUPAC Name:
magnesium(2+) sulfate
Radiolabelling:
no

Results and discussion

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 REACH 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 (1). Based on the high water solubility (360 g/L for magnesium sulphate), the substance has the potential to be absorbed by passive diffusion and may pass through aqueous pores or be carried through the epithelial barriers by the bulk passage of water. Further, the relatively low molecular weight (120.36 for magnesium sulphate) is favourable for absorption. On the other hand, magnesium sulphate being a water soluble salt, will dissociate into the magnesium cation and the sulphate anion, which will impair the passage of the gastrointestinal wall (1). Although a partition coefficient cannot be determined for this sulphate substance, it is considered to be low, due to the chemical properties, and not favourable for uptake from the gastrointestinal tract. For risk assessment 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 the substance throughout the body, by means its dissociation products, is expected based on its relatively low molecular weight and high water solubility. Based on its hydrophilic character and ion formation, the extracellularcentration is expected to be higher than intracellularcentration. It is expected that the ions will be excreted mainly via the urine (low molecular weight compounds).

 

The high melting temperature (1124˚C for magnesium sulphate) and the very low vapour pressure (considered negligible at room temperature since the melting temperature is >300˚C) indicate that it is not likely that magnesium sulphate vapours will reach the nasopharyngeal region or subsequently the tracheobronchial or pulmonary region. However, a substantial part of both substances can be inhaled via particles as these have an aerodynamic diameter below 100μm, and thus having the potential to be inhaled. For magnesium sulphate 36.5% is <10μm showing a high potential to be inhaled. Particles between 100 and 10μm will deposit in the nasopharyngeal region and subsequently be coughed or sneezed out of the body or swallowed. However, particles below 10μm mightthe tracheobronchial or pulmonary regions (2). If magnesium sulphate reach the tracheobronchial region, absorption through aqueous pores will be likely, taking the molecular weight of < 200 into account. The high water solubility of magnesium sulphate (360 g/L) is favourable for dissolution of the substance in the mucus lining of the respiratory tract. The assumed low partition coefficient of magnesium sulphate is, however, indicative for low potential of absorption directly across the respiratory tract epithelium. Overall, it is concluded that when magnesium sulphate is inhaled (particles <10μm only), absorption of these substances is to be expected, and for risk assessment purposes the inhalation absorption for magnesium sulphate is set at 50%.

 

Magnesium sulphate being a very well water soluble substance has the potential to be absorbed dermally as the surface moisture of the skin will not limit the availablility. The low molecular weight and high water solubility of magnesium sulphate is favourable for dermal uptake. Although a partition coefficient cannot be determined for this substance, it is considered to be low. The criteria for reduced dermal absorption (10%) as given in the REACH guidance, Chapter R7c. (2) (MW>500 and log Pow is smaller than -1 or higher than 4) are not met, therefore 100% dermal absorption 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 of magnesium sulphate.

Applicant's summary and conclusion