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EC number: 232-088-3 | CAS number: 7785-84-4
No guideline studies are available and therefore the discussion of the toxicokinetics is based on all available data.
TEST MATERIAL: Trisodium Trimetaphosphate
Trisodium trimetaphosphate (STMP), with formulaH3O9P3.3Na or O9P3.3Na, is a metaphosphate of sodium. The polymer can undergo ionisation with loss of H+from the –OH groups on each P in the polymer backbone. In dilute solutions there is one strongly acidic H atom for each PO4unit in the phosphate chain. There is also a relatively weakly ionised H atom associated with each end of the chain. The number of O-linked to a single cation along the polymer chain is dependent upon the positive charge on the cation. The polymer chains do undergo hydrolysis (increased in acidic conditions) to form shorter polymers and ultimately orthophosphoric acid (P2O5).
The test material is a powder, however the particle size distribution study indicates that significant exposure to the test material via particulate inhalation is not likely. No low log oil/water partition coefficient value was determined for STMP as it’s an inorganic phosphate, therefore the passage across biological membranes will be negligible. However, in comparison, the passage across the biological membrane will be aided by its low molecular weight (309) and very high water solubility (265 g/l).
Particle size distribution study has shown approximately 10% of the particle is less than 100 µm (inhalable) and 3% is less than <63 µm, thus indicating that absorption via inhalation of the substance will be minimal as the particle size of <5.5µm which is respirable will be low.
The abiotic degradation, hydrolysis as a function of pH data has shown the estimated half-live of > 1 years for pH 4, 7 and 9 at 50°C in fresh-water. However trisodium trimetaphosphate has been shown to be hydrolysed in both rats and porcine small intestine. This reaction is said to be mediated by enzymes of the brush border membrane, with the resulting metabolite being mainly orthophosphate. Both the metaphosphate and orthophosphate have ionisable group which may aid gastrointestinal tract absorption.
Trisodium trimetaphosphate is very highly water soluble (265 g/l) therefore should readily dissolve into the gastrointestinal fluid. Also the small molecular weight of 309, may aid the substance to pass through aqueous pores or be carried through the epithelium barrier by the bulk passage of water.
The very high water solubility of 265 g/l suggests that the substance is too hydrophilic to cross the lipid rich environment of the striatum corneum. Also the molecular weight of >100 and the extremely hydrophilic nature of the substance leads to the conclusion that dermal uptake of the substance will be minimal.
The results of the acute oral toxicity study in the rat showed no evidence of significant systemic toxicity; even at relatively high dose levels. This suggests that the test material is either of low toxicity or there is little absorption of the material following oral ingestion.
The water solubility of the test material would suggest that systemic distribution would be within the water component of blood. The small water-soluble molecules will diffuse through aqueous channels and pores.
Since the substance is an inorganic phosphate accumulation of test material in body fat is not likely.
Trisodium trimetaphosphate has been shown to be hydrolysed in both rats and porcine small intestine. This reaction is said to be mediated by enzymes of the brush border membrane, with the resulting metabolite being mainly orthophosphate. Both the metaphosphate and orthophosphate have ionisable group which may aid gastrointestinal tract absorption.
The very high water solubility of the test material makes it likely that the principal route of excretion will be via the kidney. Favourable to excretion by the urine as: low molecular weight, highly water soluble (265 g/l) and has ionisable groups. Any test material that is not absorbed, following oral ingestion is likely to be excreted via the faeces.
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