Tetrasodium pyrophosphate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

Study methodology is well documented and comparable to OECD guideline, however raw data is referred to but not present in the study report and therefore the conclusions of the report cannot be verified. READ ACROSS JUSTIFICATION: Read across between the following sodium and potassium pyrophosphates;   -         disodium dihydrogenpyrophosphate -         trisodium hydrogen pyrophosphate -         tertrasodium pyrophosphate -         tetrapotassium pyrophosphate   Can be justified on the following basis; All substance contain a pyrophosphate anion and either a sodium or a potassium cation.   The pyrophosphate ion is the simplest form of a condensed phosphate group. A condensed phosphate anion has one or several P-O-P bonds. As the group contains only two phosphate groups, both of the phosphorus ions are classified as “terminal phosphorus”. The pyrophosphate can undergo ionisation with loss of H+ from each of the two –OH groups on each P and therefore can occur in the -1, -2 -3 or -4 state. The degree of ionisation is dependant upon the associated cations and the ambient pH (if in solution). Therefore the above substances have a pyrophosphate anion that is likely to behave in a similar way.    In addition, the sodium and potassium cations are key elements in various cellular processes their import and export over cell membranes is regulated via pore systems and usually tightly regulated. As such, the presence of such cations is not expected to have an impact on the genotoxicity of the substances detailed above therefore as the pyrophosphate anion is common the results of genotoxicity studies can be reliably read-across within the group.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1974

Report date:

1974

Reference 2

Reference Type:

publication

Title:

Unnamed

Year:

1978

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 478 (Genetic Toxicology: Rodent Dominant Lethal Test)

Deviations:

no

GLP compliance:

no

Remarks:

Study predates GLP

Type of assay:

rodent dominant lethal assay

Test material

Test material information

Constituent 1

Reference substance name:

Disodium dihydrogenpyrophosphate

EC Number:

231-835-0

EC Name:

Disodium dihydrogenpyrophosphate

Cas Number:

7758-16-9

Molecular formula:

H2Na2O7P2

IUPAC Name:

disodium [hydroxy(oxido)phosphoryl] hydrogen phosphate

Details on test material:

- Name of test material (as cited in study report): sodium acid pyrophosphate
- Analytical purity: no data
- Lot/batch No.: no data

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Simonsen Laboratories, Gilroy, California
no data on age/weight of animals.

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

- Vehicle(s)/solvent(s) used: water(administered as a suspension)
- Justification for choice of solvent/vehicle: Solubility of the compound was investigated with various solvents to determine the most appropriate vehicle for administration. Because of the low toxicity of the material and consuquent high dosage required the test material was administered as a suspension.

Duration of treatment / exposure:

Acute study: single oral dose
Subacute study: 5 days

Frequency of treatment:

Acute study: once
Subacute study: 1 dose per day, 24 hours apart for 5 days

Post exposure period:

not applicable

Doses / concentrations

Remarks:

Doses / Concentrations:
720, 72, 7.2 mg/kg
Basis:
no data

No. of animals per sex per dose:

Acute study: 10 males
Subacute study: 10 males

Control animals:

yes, concurrent vehicle

Positive control(s):

triethylenemelamine
- Justification for choice of positive control(s):substance is a known mutagen
- Route of administration: single i.p injection
- Dose: 0.2 mg/kg

Examinations

Tissues and cell types examined:

Procedure is designed to indicate possible mutagenic effects in male sperm. Effects are seen in fetal development.

Details of tissue and slide preparation:

No data

Evaluation criteria:

The following parameters indicate effects in dominant lethal studies:
- total implants (live fetuses plus early and late fetal deaths)
- total dead (early and late fetal deaths)
- dead implants per total implants
- pre-implantation loss (calculted as the difference between the total corpora lutea and total implant counts)
total corpora lutea was also evaluated because a significant change of this parameter could influence the significance of the pre-implantation loss.

Statistics:

Total implants, total dead, total corpora lutea, and pre-implantation loss parameters were analysed for significance by the t-test (Federer WT, Experimental design (theory and application), The Macmillan Company, 1955).

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Any other information on results incl. tables

The biological criteria used to evaluate mutagenic effects in the rat showed no consistant responses that could be attributed to treatment. Some occasional statistical differences between the control and test material groups were random and did not suggest a time or dose-response effect.

Tabulated data was not included in study report.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Review and statistical analysis of the data do not show sodium acid pyrophosphate (FDA No. 71-61) to b ea mutagen in the rat by the dominant lethal test.