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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian germ cell study: cytogenicity / chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
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.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974
Reference Type:
publication
Title:
Unnamed
Year:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
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

Reference
Name:
Unnamed
Type:
Constituent
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 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 be a mutagen in the rat by the dominant lethal test.