Registration Dossier

Administrative data

Endpoint:
basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
key study
Study period:
Not applicable
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Theoretical assessment taking all currrently available relevant information into account, based on the REACH Guidance: Guidance on Information Requirements and Chemical Safety Assessment, Chapter R.7c Endpoint specific guidance. Since this is a theoretical assessment, the Klimisch value cannot be 1.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Guidance for the implementation of REACH. Guidance on information requirements and chemical safety assessment. Chapter R.7c: Endpoint specific guidance. European Chemical Agency, May 2008
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Not applicable

Results and discussion

Main ADME results
Type:
absorption
Results:
For risk assessment purposes, 50% is used for oral, dermal and inhalation absorption.

Any other information on results incl. tables

TOXICOKINETIC ASSESSMENT

A substance can enter the body via the gastrointestinal tract, the lungs, or the skin, depending on the exposure route. To determine the rate of absorption, the different routes are assessed individually.

After oral administration, in general, a compound needs to be dissolved before it can be taken up from the gastro-intestinal tract. Strontiumhydrogenphosphate has a low water solubility (62.1 mg/L at 20°C), therefore passive diffusion (passage of small water-soluble molecules through aqueous pores or carriage of such molecules across membranes with the bulk passage of water) is expected. However, as soon as strontiumhydrogenphosphate dissolves in the fluids of the gastro-intestinal tract, it will dissociate into a phosphate-ion and a strontium-ion. It is generally assumed that ionized substances do not readily diffuse across biological membranes, but the absorption of ionic substances (i.e. acids and bases) is influenced by the varying pH of the GI tract. There is no information on the log Pow of this compound, but based on its inorganic nature its solubility in organic solvents is expected to be limited. This characteristic will hamper penetration through lipid membranes. Due to its low water solubility, its ionized state and its limited ability to penetrate biomembranes, for risk assessment purposes oral absorption of strontiumhydrogenphosphate is set at 50%. The oral toxicity data do not provide reason to deviate from the proposed oral absorption factor.

 

Once absorbed, wide distribution of the substance throughout the body is expected based on its low molecular weight. Absorbed strontiumhydrogenphosphate is most likely excreted via urine. Strontium ions have a high chemical similarity to Calcium ions. Strontium ions have a tendency to replace Calcium ions from biological tissues, most importantly from bones. As a consequence, Strontium ions have a high potential to bio-accumulate in the body upon exposure. It is of note that this is a reversible process.

 

Based on the absence of a melting point below 300°C, strontiumhydrogenphosphate is expected to have a low vapour pressure. This would imply that exposure via inhalation of vapour of strontiumhydrogenphosphate is not likely to occur. Furthermore, the density of the test substance has been shown to be relatively high, with a relative density of 3.55, which means that dust formation is unlikely to occur. On the other hand, the strontiumhydrogenphosphate particles are on average 32 µm, thus relatively small with a narrow size distribution of 10% < 11.3 μm, 50% < 16.9 μm and 90% < 25.4 μm. As a rough guide, particles with aerodynamic diameters below 100 μm have the potential to be inspired. Particles with aerodynamic diameters below 50 μm may reach the thoracic region and those below 15 μm the alveolar region of the respiratory tract. This indicates that if strontiumhydrogenphosphate particles would reach the lungs, both the nasopharyncheal region and subsequently the tracheo/bronchial/pulmonary region would be reached. Once strontiumhydrogenphosphate reaches the lung tissue, it will -to some extent- dissolve within the mucus lining of the respiratory tract and get absorbed due to its low water solubility and low molecular weight. However, the ionized state in which it will occur will hamper uptake. Based on the above data, for risk assessment purposes the inhalation absorption of strontiumhydrogenphosphate is set at 50%. The results of the inhalation toxicity study do not provide reasons to deviate from this proposed inhalation absorption factor.

 

Strontiumhydrogenphosphate is a powder. Dissolving into the surface moisture of the skin can happen to some extent, given the fact that strontiumhydrogenphosphate has a low water solubility. Upon dissolving, the substance will dissociate into strontium- and phosphate ions. Crossing the first layer of the skin, the stratum corneum, will be hampered by its ionized state, therefore dermal absorption is likely to be low. According to the criteria given in the ECHA REACH Guidance, 10% dermal absorption will be considered in case MW >500 and log Pow <-1 or >4, otherwise 100% dermal absorption should be used. As the physical/chemical properties of strontiumhydrogenphosphate do not meet the criteria for limited dermal absorption (MW 183.6), for risk assessment purposes dermal absorption should be set at 100%. It is, however, generally accepted that dermal absorption is lower compared to oral absorption, and therefore a dermal absorption of 50% is considered to be more appropriate.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
For risk assessment purposes, 50% is used for oral, dermal and inhalation absorption.