Trisodium trimetaphosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

documentation insufficient for assessment

Data source

Reference

Reference Type:

publication

Title:

The hydrolysis and excretion of polymeric phosphate

Author:

Gosselin RE, Rothstein A, Miller GJ, Berke HL

Year:

1952

Bibliographic source:

J Pharmacol Exp Ther.; 106(2):180-92; PMID: 12981640

Materials and methods

Objective of study:

absorption

excretion

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Metabolism and urinary excretion of sodium trimetaphosphate, sodium tripolyphosphate, or sodium hexaphosphate were studied in rabbits. To this purpose, the phosphates were injected intravenously and the animals then placed in metabolic cages. Blood samples and urine were obtained and analysed on orthophosphates and acid-hydrolysable phosphates called ‘labile phosphates’.

GLP compliance:

no

Remarks:

Study pre-dates GLP

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium trimetaphosphate

EC Number:

232-088-3

EC Name:

Trisodium trimetaphosphate

Cas Number:

7785-84-4

Molecular formula:

H3O9P3.3Na or O3P3.3Na

IUPAC Name:

Sodium trimetaphosphate

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Trimetaphosphate
- Analytical purity: no data

Radiolabelling:

no

Test animals

Species:

rabbit

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Fasting period before study: 18-24h
- Individual metabolism cages: yes

Administration / exposure

Route of administration:

intravenous

Vehicle:

water

Details on exposure:

intravenous exposure

Duration and frequency of treatment / exposure:

no data

Doses / concentrations

Remarks:

Doses / Concentrations:
25.2 mg phosphorus/kg bw equiivalent to 249 mg/kg bw trisodium trimetaphosphate

No. of animals per sex per dose / concentration:

one animal

Control animals:

yes, concurrent no treatment

Results and discussion

Toxicokinetic / pharmacokinetic studies

Details on distribution in tissues:

After intravenous injection of trisodium trimetaphosphate, the compound was rapidly removed from the plasma at rates which were approximately exponential. The compound produced no changes in the serum concentration of orthophosphate until late in the experiment, when a small upward trend was noted.

Details on excretion:

During water diuresis of rabbits, excretion of orthophosphate remained relatively constant; labile phosphorus was generally not detectable during these control periods.
After injection of trisodium trimetaphosphate, the compound appeared promptly in the urine, but after three hours, only small amounts were detectable, in conformity with plasma concentrations. The total amount excreted within 3 hours is about 60% of the injected dose. The excretion of orthophosphate also rose following the injections from 23 µg/min to 83, 56, and 44 µg/min in three 20 min intervals, suggesting a hydrolytic metabolism of the metaphosphate. No more than 2 % of the administered polymer could be detected as extra orthophosphate in the urine, the vast majority appeared as labile (presumably polymeric) phosphate.

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

The only metabolite arising from sodium trimetaphosphate metabolism was the orthophosphate anion.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
After intravenous injection of 249 mg/kg bw trisodium trimetaphosphate into rabbits, plasma concentration of polymeric (‘labile’) phosphate declined almost exponentially. At best a slight increase in serum orthophosphate concentration (resulting from metaphosphate hydrolysis) was visible. Urinary excretion followed the decline in serum phosphate quite well, the vast majority of metaphosphate was excreted unhydrolysed.

Executive summary:

To study metabolism and urinary excretion of sodium trimetaphosphate, sodium tripolyphosphate, and sodium hexaphosphate, these substances were administered to rabbits. Subsequently, animals were placed in metabolic cages, blood and urine samples were obtained and analysed on orthophosphates and acid-hydrolysable phosphates called ‘labile phosphates’.

After intravenous injection of 249 mg/kg bw trisodium trimetaphosphate into rabbits, plasma concentration of polymeric (‘labile’) phosphate declined almost exponentially. At best a slight increase in serum orthophosphate concentration (resulting from metaphosphate hydrolysis) was visible. Urinary excretion followed the decline in serum phosphate quite well, the vast majority of metaphosphate was excreted unhydrolysed. Alltogether, about 60% of the administered dose was excreted in urine within 3h.