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Toxicological information

Basic toxicokinetics

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basic toxicokinetics
Type of information:
other: expert statement
Adequacy of study:
key study
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Based on the current knowledge the statement has been written.

Data source

Reference Type:
study report

Materials and methods

Objective of study:
Principles of method if other than guideline:
no guideline as it is an expert statement
GLP compliance:

Test material

Test material form:
solid: particulate/powder
Details on test material:
No additional data available.

Results and discussion

Main ADME results
The oral absorption is considered to be 50%, the inhalation absorption 100% and the dermal absorption 10%.

Toxicokinetic / pharmacokinetic studies

Details on absorption:
Based on low MW, high water solubility, assumed low logPow high oral absorption is expected. Therefore, 50% absorption is taken for oral exposure and 10% for inhalation and dermal 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) Intestinal absorption of water-soluble constituents of SSP and TSP may appear likely.(2) However,Ca2+is an essential ion in all organisms, where it plays a crucial role in processes ranging from the formation and maintenance of the skeleton to the temporal and spatial regulation of neuronal function (3). The Ca2+balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. An adult ingests on averageCa2+daily from whichis absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones. To maintain the Ca2+balance, the kidney must excrete the same amount of Ca2+that the small intestine absorbs. This is accomplished by a combination of filtration of Ca2+across the glomeruli and subsequent re-absorption of the filtered Ca2+along the renal tubules. Bone turnover is a continuous process involving both resorption of existing bone and deposition of new bone. The above-mentioned Ca2+fluxes are stimulated by the synergistic actions of active vitamin D (1,25-dihydroxyvitamin D3) and parathyroid hormone.

Phosphate (4) is a major intracellular anion which participates in providing energy for metabolism of substances and contributes to important metabolic and enzymatic reactions in almost all organs and tissues. Phosphate exerts a modifying influence on calcium concentrations, a buffering effect on acid-base equilibrium, and has a major role in the renal excretion of hydrogen ions. Phosphate is absorbed from, and to a limited extent secreted into, the gastrointestinal tract. Transport of phosphate from the gut lumen is an active, energy-dependent process that is modified by several factors. Vitamin D stimulates phosphate absorption, an effect reported to precede its action on calcium ion transport. In adults, about two thirds of the ingested phosphate is absorbed, and that which is absorbed is almost entirely excreted into the urine. In growing children, phosphate balance is positive. Concentrations of phosphate in plasma are higher in children than in adults.

Absorption of sulphate depends on the amount ingested. 30 - 44% of sulfate was excreted in the 24-h urine after oral administration of magnesium or sodium sulfate (5.4 g sulfate) in volunteers. At high sulphate doses that exceed intestinal absorption, sulphate is excreted in feces. Intestinal sulphate may bind water into the lumen and cause diarrhoea in high doses. Sulphate is a normal constituent of human blood and does not accumulate in tissues. Sulphate levels are regulated by the kidney through a reabsorption mechanism. Sulphate is usually eliminated by renal excretion. It has also an important role in the detoxification of various endogenous and exogenous compounds, as it may combine with these to form soluble sulphate esters that are excreted in the urine (5).


For risk assessment purposes oral absorption of SSP and TSP constituents is set at 50%. The results of the toxicity studies do not provide a reason to deviate from this proposed oral absorption.


Due to the low vapour pressure of SSP and TSP (<8.40x10-7)it is not to be expected that their constituents will reach the nasopharyncheal region or subsequently the tracheobronchial or pulmonary region. Also, only particles with aerodynamic diameters below 100µm have the potential to be inhaled by humans,and the MMADs of SSP and TSP are much higher than 100µm. Constituents with low water solubility reaching the lungs (particle size <10 µm)might be retained in the mucus and transported out of the respiratory tract.(2)For risk assessment purposes the inhalation absorption of SSP and TSP constituents is set at 100%.


Dry particulates will have to dissolve into the surface moisture of the skin before uptake can begin. Water-soluble constituents of SSP and TSP have potential to partition from the stratum corneum into the epidermis.(2) The log P value will be very low (below 0) and may be too hydrophilic to cross the lipid rich environment of the stratum corneum. Therefore, 10% dermal absorption of SSP and TSP constituents is proposed for risk assessment purposes.

Applicant's summary and conclusion