Trisodium hydrogen diphosphate

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

Publication, data reported at summary level.

Justification for type of information:

Study submitted on analogous substance as supporting data only.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1985

Materials and methods

Objective of study:

other: Intestinal resorption, excretion and balance of phosphates with different chain length

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Mini-pigs were fed basic diets supplemented with 4 different phosphates of increasing chain length. The balance of uptake and excretion via urine and faeces was determined over period of 22 - 26 days.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Tetrasodium pyrophosphate

EC Number:

231-767-1

EC Name:

Tetrasodium pyrophosphate

Cas Number:

7722-88-5

Molecular formula:

Na4P2O7

IUPAC Name:

tetrasodium phosphonato phosphate

Test material form:

not specified

Details on test material:

- Name of test material (as cited in study report): Tetrasodium pyrophosphate (Na4P2O7)

- Other substances tested: Disodium hydrogen phosphate (Na2HPO4), Sodium polyphosphate (Na5P3O10), Graham Salt ((NPO3)x)

Radiolabelling:

no

Test animals

Species:

pig

Strain:

other: Göttingen miniature pigs

Sex:

male

Details on test animals or test system and environmental conditions:

no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Duration and frequency of treatment / exposure:

Pre-period: 2 - 6 days
Supplemental phase I: 6 - 7 days
Supplemental phase II: 3 - 7 days
Supplemental phase III: 4 - 5 days
Post phase: 3 - 4 days

Doses / concentrations

Remarks:

Doses / Concentrations:
0.9 - 3.6 g per animal and day

No. of animals per sex per dose / concentration:

8

Control animals:

no

Results and discussion

Preliminary studies:

No studies reported.

Toxicokinetic / pharmacokinetic studies

Details on excretion:

See Table 1 and 2

Any other information on results incl. tables

Essentially there was an equilibrated balance between intake and excretion.

Table 1 shows that the urinary excretion of higher linear condensed phosphates is lower, indicating a lower intestinal resorption.

Table 1: Uptake and urinary excretion of phosphates of different phosphate supplements

	Supplement	Additional excretion		Average
	(g P/day	(g P/day)	(%)	(%)
Na2HPO4	1.0	0.18	18
	3.2	0.71	23	21.6
	2.2	0.53	24
Na4P2O7	1.2	0.21	18
	3.6	0.69	19	22.0
	2.2	0.64	29
Na5P3O10	1.2	0.25	21
	3.3	0.66	20	22.3
	2,1	0.53	26
(NaPO3)x	0.9	0.04	5
	2.9	0.33	11	9.8
	2.0	0.20	13

Table 2 shows the equilibrated balances. Again, in the polycondensed phosphates the decreasing urinary while increasing fecal excretion points to a reduced intestinal resorption.

Table 2: Balance of phosphates (per animal and day) per period, all values in g/day

 

TrialPeriod		Phosph.	Phosph. Excretion		Balance
		Input	Urine	Feces
Trial I	pre period	1.82	0.37	1.56	-0.11
NaHPO4	1. Supplement	2.83	0.55	2.30	-0.02
	2. Supplement	5.20	1.09	3.60	+0.51
	3. Supplement	4.04	0.90	3.25	-0.11
	post period	1.82	0.43	1.85	-0.26
Trial II	pre period	1.72	0.32	1.50	-0.10
Na4P2O5	1. Supplement	2.94	0.53	2.32	+0.08
	2. Supplement	5.36	1.01	3.40	+0.94
	3. Supplement	3.91	0.96	2.84	+0.10
	post period	1.72	0.38	1.72	-0.37
Trial III	pre period	1.98	0.32	1.70	-0.04
Na5 P3O10	1. Supplement	3.15	0.56	2.48	+0.11
	2. Supplement	5.25	0.98	4.12	+0.15
	3. Supplement	4.08	0.85	3.29	-0.06
	post period	1.98	0.50	1.67	-0.19
Trial IV	pre period	1.98	0.39	1.84	-0.24
(NaPO3)x	1. Supplement	2.85	0.43	2.39	+0.04
	2. Supplement	4.89	0.72	4.04	+0.14
	3. Supplement	4.02	0.65	3.29	+0.08
	post period	1.98	0.42	1.58	-0.02

The conclusion is that increasing phosphate input induces increased phosphate output in an equilibrated fashion. The phosphate, calcium and magnesium levels in serum were not altered. The dose of up to 5 g phosphate/animal/day is considered as high.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): no bioaccumulation potential based on study results
Doses of up to 5 g phosphorous/animal/day in the form of 4 different sources (disodium hydrogen phosphate, tetrasodium pyrophosphate, sodium tripolyphosphate or Graham salt) resulted in an equilibrated balance and were well tolerated. With longer P chains the intestinal resorption appears to decrease.

Executive summary:

Eight adult male minipigs were offered a commercial low phosphorous basic diet which was supplemented over 3 trial periods (4 - 7 days each) with either disodium hydrogen phosphate, tetrasodium pyrophosphate, sodium tripolyphosphate or Graham salt at a dose of 0.9 - 3.6 g/animal/day.

From the determinations of phosphorous in diet, feces and urine, it was concluded that, independent of the length of the polyphosphate chain, output and intake were equilibrated. With long-chain phosphate at high doses, a lower urinary P excretion corresponds with higher fecal P excretion.

The animals adapted well to the increased phoshorous diet.