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Description of key information

Short description of key information on bioaccumulation potential result: 
Ca2+ and phosphate, the main forms to which the submission substance dissociates in aquatic environments, are both essential components of all body tissues. They are activily taken up from the gastrointestinal tract and their concenttrations are homeostatically controlled. Sulfate is taken up from soluble forms to approx. 30% in the gastrointestinal tract. Uptake of humic acids from the gastrointestinal tract is low.
No information is available on the dermal absorption of the submission substance through the skin, but is expected to be low due to the ionic form.
For risk assessment purposes in a conservative approach oral absorption of the submission substance is set at 50%, inhalation absorption 100% and dermal absorption 10%.

Key value for chemical safety assessment

Bioaccumulation potential:
no bioaccumulation potential
Absorption rate - oral (%):
50
Absorption rate - dermal (%):
10
Absorption rate - inhalation (%):
100

Additional information

Oral absorption

In aqueous environments, such as body fluids, the submission substance is expected to dissociate mainly into Calcium (Ca2+) and phosphate ions (PO43 -), partly into calcium and sulfate ions and small amount of humic acid.

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. The Ca2+balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. The recommended daily intake of Ca2+from food is 1000 mg/day and 1300 mg/day for adolescents, which is absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones (Brunton, 2006: Goodman and Gilman’s: The Pharmacological Basis of Therapeutics).

Phosphate 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 as orthophosphate. 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. Excretion occurs mainly via the urine (Brunton, 2006: Goodman and Gilman’s: The Pharmacological Basis of Therapeutics).

Calcium from Calcium sulfate was well absorbed in an experimental study with human volunteers. Six female volunteers were orally administerd a capsule containing 135 mg Ca sulfate, including 36 mg calcium-44. Total feces were collected for 12 days after isotope ingestion. All stools were weighted and combined in 3-4 day pools. Isotopic abundance of calcium was determined by high-resolution fast atom bombardement mass spectrometry. Mean calcium absorption after single oral administration to six female volunteers was reported to be 41% (Martin et al. 2002).

Absorption of sulfate depends on the amount ingested. Approx. 30% of sulfate was excreted in the 24-h urine after oral administration of magnesium sulfate (5.4 g sulfate) in volunteers . At high sulfate doses that exceed intestinal absorption, sulfate is excreted in faeces. Intestinal sulfate may bind water into the lumen and cause diarrhoea in high doses (Morris ME, Levy G.,J. Toxicol. Clin. Toxicol.1983; 20(2), 107-14).

Sulfate is a normal constituent of human blood and does not accumulate in tissues. Sulfate levels are regulated by the kidney through a reabsorption mechanism. Sulfate is usually eliminated by renal excretion.

Absorption of humic acids from the gastrointestinal tract is low. Absorption in the isolated gastrointestinal tract of rats was <1% (EMEA, 1999: EMEA/MRL/554/99 -Final; http://www.ema.europa.eu/docs/en_GB/document_library/Maximum_Residue_Limits_-_Report/2009/11/WC500014416.pdf).

Inhalative and dermal absorption

No specific information is available for inhalative and dermal absorption. In a conservative approach 100% absorption for inhalation is assumed.

According to the EPA report on dermal exposure, Kp values (permeability coefficient for chemical from an unspecified vehicle through the skin) near 10 exp-3 cm/hour (substantially lower than those of most organic compounds) and a few even lower values are observed for inorganic substances. Accordingly, a default assumption of 10-3 cm/hour is recommended by US EPA for inorganics that have not been tested (indicating a low level of dermal absorption). Based on this Kp a low absorption rate through the skin can be assumed. Others propose dermal absorption factors for metal cations of maximal 1% for inorganics (HERAG fact sheet). All in all, in a conservative approach dermal absorption of inorganics can be assumed to be < 10 %.

Discussion of bioaccumulation potential

In aqueous environments, such as body fluids, the submission substance is expected to dissociate mainly into Calcium (Ca2+) and phosphate ions (PO43 -), partly into calcium and sulfate ions and small amount of humic acid.

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. The Ca2+balance is maintained by the concerted action of three organ systems, including the gastrointestinal tract, bone, and kidney. The recommended daily intake of Ca2+from food is 1000 mg/day and 1300 mg/day for adolescents, which is absorbed in the small intestine by a mechanism that is controlled primarily by the calciotropic hormones (Brunton, 2006: Goodman and Gilman’s: The Pharmacological Basis of Therapeutics).

Phosphate 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 as orthophosphate. 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. Excretion occurs mainly via the urine (Brunton, 2006: Goodman and Gilman’s: The Pharmacological Basis of Therapeutics).

Approx. 30% of sulfate was excreted in the 24-h urine after oral administration of magnesium sulfate (5.4 g sulfate) in volunteers. At high sulfate doses that exceed intestinal absorption, sulphate is excreted in faeces. Intestinal sulfate may bind water into the lumen and cause diarrhoea in high doses (Morris ME, Levy G., J. Toxicol. Clin. Toxicol.1983; 20(2), 107-14). Sulfate is a normal constituent of human blood and does not accumulate in tissues. Sulfate levels are regulated by the kidney through a reabsorption mechanism. Sulfate is usually eliminated by renal excretion.

Absorption of humic acids from the gastrointestinal tract is considered to be low (see above). As humic acid has a very large molecular weight, bioaccumulation of humic acid is considered to be unlikely.