Sodium metaphosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Enzymic hydrolysis of polyphosphate in the gastrointestinal tract

Author:

Ivey FJ, Shaver K

Year:

1977

Bibliographic source:

J. Agric. Food Chem., 25(1): 128–30; DOI: 10.1021/jf60209a021

Materials and methods

Objective of study:

metabolism

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Aqueous solutions of different sodium meta- and polyphosphates were incubated in isolated small intestine obtained from rat or pig. The resulting phosphate species were analyzed by the paper chromatography method according to Karl-Krupa (Anal. Chem. 1956, 28: 1091) with slight modifications. Two-dimensional development was used for analysis of the hexametaphosphate samples.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sodium metaphosphate

EC Number:

233-343-1

EC Name:

Sodium metaphosphate

Cas Number:

10124-56-8

Molecular formula:

H6O18P6.6Na

IUPAC Name:

Sodium metaphosphate

Constituent 2

Reference substance name:

sodium hexametaphosphate

IUPAC Name:

sodium hexametaphosphate

Details on test material:

- Name of test material (as cited in study report): sodium hexametaphosphate

Radiolabelling:

no

Test animals

Species:

other: rat and pig

Strain:

other: rat: Wistar; pig: no data

Sex:

not specified

Details on test animals or test system and environmental conditions:

Adult male Wistar derived rats of about 250 g were fasted for 2 days to clear the intestine and then sacrificed with CO2. The small intestine was immediately excised. The small intestine was flushed with 20 ml of warm saline and tied off into thee sections.
Porcine small intestines were excised from hogs during slaughter at a local slaughter house and were taken to the laboratory. The first 2 m of each small intestine was used. These were flushed with 200 ml of warm saline and cut into 50 cm sections.

Administration / exposure

Route of administration:

infusion

Vehicle:

water

Details on exposure:

In each section of the tied rat intestine, 1 mL of 3% phosphate salt solution was injected. The phosphate solutions had been adjusted to pH 7.5 with 0.2 N NaOH or 0.5 N HCl prior to use. The sections were incubated in 37°C saline for 10, 30, and 60 minutes. After the period of incubation, the section was cut above a funnel and the contents and a 3 mL saline wash were collected and frozen until analysed. Two intestines were used per salt and the sections of each intestine used for each incubation period were randomised.
The tied sections of porcine small intestine were filled with 25 ml of 3% phosphate solution and incubated in 37°C saline for 10, 30, and 60 minutes. After the period of incubation, the section was cut above a funnel and the contents and a 50-ml saline wash were collected and frozen until analysed. The phosphate solutions had been adjusted to pH 7.5 with 0.2 N NaOH or 0.5 N HCl prior to use. One intestine was used per salt and the sections used for incubation periods were randomised.

Duration and frequency of treatment / exposure:

24 hours

Doses / concentrations

Remarks:

Doses / Concentrations:
not applicable

No. of animals per sex per dose / concentration:

not applicable

Control animals:

no

Results and discussion

Preliminary studies:

not performed

Toxicokinetic / pharmacokinetic studies

Details on absorption:

not examined

Details on distribution in tissues:

not examined

Details on excretion:

not examined

Metabolite characterisation studies

Metabolites identified:

yes

Details on metabolites:

Hydrolysis of polyphosphates occurred rapidly in in vitro rat intestine. In 60 minutes, metaphosphates with n>4 are substantially hydrolyzed (Table 1). This rate suggests that enzymatic hydrolysis is likely to be involved, since for polyphosphates with n>4 at best marginal hydrolysis in water is reported at this pH.
Porcine intestine also gave significant hydrolysis of both ring and chain phosphates (Table 2). In general, the rate of hydrolysis for each compound was similar to that in rat intestine.
Identified metabolites comprised ortho-, pyro-, trimeta-, tripoly-, and tetrapolyphosphates, as depicted in tables 1 and 2.

Any other information on results incl. tables

Table 1: Phosphate distribution with time of incubation at 37°C in rat small intestine (average of 2 determinations per salt).

	Time [min]	Ortho	Pyro	Trimeta	Tripoly	Tetrameta	Tetrapoly	n>4
Sodium trimeta-phosphate	0	1.1	4.3	0.3	95.7
	10	42.1	8.9	0.4	48.7
	30	80.7	4.2	0.2	15.0
	60	74.8	7.5	0.0	17.7
Sodium trimeta-phosphate	0	0.5	0.6	96.9	2.0
	10	4.0	0.3	91.9	3.8
	30	13.9	0.3	82.5	3.2
	60	25.8	0.4	72.5	1.3
Sodium hexameta-phosphate	0	1.0	1.0	1.8	1.5	1.1	1.7	90.8
	10	10.1	1.0	5.8	1.6	0.0	2.0	79.6
	30	14.7	0.4	4.2	1.0	0.0	1.0	78.6
	60	15.5	0.4	3.6	0.9	0.0	0.9	78.9

 

Table 2: Phosphate distribution with time of incubation at 37°C in porcine small intestine (average of 2 determinations per salt).

	Time [min]	Ortho	Pyro	Trimeta	Tripoly	Tetrameta	Tetrapoly	n>4
Sodium trimeta-phosphate	0	1.1	4.3	0.3	95.7
	10	8.0	10.0	0.5	81.5
	30	11.5	12.7	0.6	75.2
	60	18.1	16.4	0.6	65.0
Sodium trimeta-phosphate	0	0.5	0.6	96.9	2.0
	10	6.6	0.8	91.6	1.1
	30	8.4	1.0	88.8	1.8
	60	10.9	2.0	86.8	1.5
Sodium hexameta-phosphate	0	1.0	1.0	1.8	1.5	1.1	1.7	90.8
	10	9.0	1.2	3.9	1.4	0.0	1.5	80.1
	30	7.5	1.5	8.8	1.5	0.0	1.8	78.9
	60	12.5	0.7	7.3	1.5	0.0	1.2	75.9

 

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
Linear as well as circular polyphosphates are hydrolysed in both rat and porcine small intestine. This reaction is mediated by enzymes of the brush border membrane. The resulting metabolite is mainly orthophosphate.

Executive summary:

Cyclic ring as well as linear polyphosphates including sodium trimeta-, tetrameta-, tripoly-, and hexametaphosphate (Graham's salt) were found to be enzymatically hydrolyzed in in vitro rat and porcine small intestine.

Sodium trimetaphosphate was reduced by 27.5% and 13.2% in rat and porcine small intestine after 1h, respectively. Sodium hexametaphosphate was reduced by 21.1% and 24.1% in rat and porcine small intestine after 1h, respectively. Sodium tripolyphosphate was reduced by 82.3% and 35% in rat and porcine small intestine after 1h, respectively.

The rate of hydrolysis in the in vitro intestine indicated an enzymic mechanism. The lack of polyphosphatase activity in heat treated intestines, with normal hydrolysis in intestines treated with antibiotic, confirms previous reports of phosphatase activity on the intestinal brush border membrane.