Trisodium orthophosphate

Endpoint summary

Description of key information

Short description of key information on bioaccumulation potential result: 
A number of toxicokinetics literature papers are available for sodium and potassium orthophosphates. These are not however considered to be equivalent to a TK study and therefore no key study is submitted and the TK assessment is based on all the data in the dossier.

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Additional information

TEST MATERIAL: Group 1i: Monophosphates (orthophosphates, with sodium and potassium cation)

 

Substances to be considered:

 

IP N^o	Substance name	CAS N^o	EINECS N^o	Molecular weight
2	Sodium dihydrogenorthophosphate	7558-80-7	231-449-2	120-121
3	Disodium hydrogenorthophosphate	7558-79-4	231-448-7	142-144
4	Trisodium orthophosphate	7601-54-9	231-509-8	164-167
12	Potassium dihydrogenorthophosphate	7778-77-0	231-913-4	136-137
13	Dipotassium hydrogenorthophosphate	7758-11-4	231-834-5	175
14	Tripotassium orthophosphate	7778-53-2	231-907-1	214
55	Potassium pentahydrogen bis(phosphate)	14887-42-4	238-961-5	212

 

 

 

The substances to be considered are monophosphates also known as orthophosphates. The ionic form of the Group IA alkali metals is M⁺. Sodium and potassium are naturally abundant and the salts of these metals tend to be soluble. Both sodium and potassium are essential elements in nature.

 

The Inorganic phosphates (monophosphate/orthophosphates) were grouped based on the structure of the phosphate ions firstly, then grouped accordingly to their cation identity. Group 1i includes the following substances: Sodium dihydrogenorthophosphate (MW: 120-121), Disodium hydrogenorthophosphate(MW:142-144), Trisodium orthophosphate(MW:164-167), potassium dihydrogenorthophosphate(MW:136-137), Tripotassium hydrogenorthophosphate(MW:175), Tripotassium orthophosphate (MW:214) and Potassium pentahydrogen bis(phosphate) (MW:212). All substances are highly water soluble.

 

All materials are powders; the particle size distribution study indicates that significant exposure to the test material via particulate inhalation is likely and should therefore be considered. No oil/water partition coefficient value was determined for Group 1i as the substances are inorganic in nature.

As sodium and potassium orthophosphates are inorganic the passage across biological membranes will be negligible as they are likely to be predominantly hydrophilic in nature. However, passage across the biological membrane will be aided by relatively low molecular weights and very high water solubility ( >10000 mg/L).

 

TOXICOKINETICS OF TRISODIUM ORTHOPHOSPHATE:

 

Absorption

 

A particle size distribution study has shown approximately Ca. 42% of the particles are less than 100 µm (inhalable). As the substance is not lipophilic it would not have the potential to be absorbed directly across the respiratory tract epithelium. However the very high water solubility of the substances and the low molecular weights does indicate that it has the potential to be absorbed through aqueous pores or be retained in the mucus. Particles deposited on the mucociliary blanket will be swallowed in the mouth (ingestion). Therefore absorption from the gastrointestinal tract will contribute to the total systemic burden of the substance that is inhaled.

 

No experimental determination of the abiotic degradation, hydrolysis as a function of pH was performed using Method 111 of the OECD Guidelines for Testing of Chemicals, 13 April 2004, since the phosphate anion has no potential mechanism for further hydrolysis, itself being the final common hydrolysis product of higher polyphosphates. Orthophosphates do however, contain ionisable groups which may aid gastrointestinal tract absorption.

 

The group 1i substances are very highly water soluble (>10000 mg/l) therefore should readily dissolve into the gastrointestinal fluid. Also small molecular weights (120-214), may aid the substance to pass through aqueous pores or to be carried through the epithelium barrier by the bulk passage of water.

 

The very high water solubility 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.

 

 

Distribution

 

The water solubility of the test material would suggest that systemic distribution would be within the water component of blood (serum). 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 favourable.

 

 

Metabolism

 

The high water solubility of the test material does suggest that there is unlikely to be any significant metabolism. The results of the in vitro genotoxicity assays the substance itself and similar materials showed that genotoxicity was neither enhanced nor diminished in the presence of S9 metabolising system.

 

Excretion

 

The very high water solubility of the test material makes it likely that the principal route of excretion will be via the kidney. Such substances are favourable to excretion by the urine due to their low molecular weight, highly water soluble nature and ionisable groups. Any test material that is not absorbed, following oral ingestion is likely to be excreted via the faeces.