Disodium fluorophosphate

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Study period:

No data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Study is comparable to OECD guideline 475 but has the following restrictions. OECD 475 states that samples should be taken at two different times following treatment, however only one sample was taken at 30 hours post-treatment. This study is conducted according to an appropriate guideline and is therefore considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint.

Data source

Reference

Reference Type:

publication

Title:

Mutagenicity of cosmetics ingredients licensed by the European Communities

Author:

Gocke E, King MT, Eckhardt K & Wild D

Year:

1981

Bibliographic source:

Mutation Research, 90: 91-109

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)

Deviations:

yes

Remarks:

Only one sample was taken following treatment

Principles of method if other than guideline:

not applicable

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Disodium fluorophosphate

EC Number:

233-433-0

EC Name:

Disodium fluorophosphate

Cas Number:

10163-15-2

Molecular formula:

FH2O3P.2Na

IUPAC Name:

disodium fluorophosphate

Details on test material:

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

Test animals

Species:

mouse

Strain:

NMRI

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: S. Ivanovas GmbH
- Age at study initiation: no data
- Weight at study initiation: no data
- Diet (e.g. ad libitum): Standard chow (Altromin GmbH, Lage, Germany), ad libitum
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: Hanks' blanaced salt solution
- Concentration of test material in vehicle: no data

Details on exposure:

not applicable; IP administration

Duration of treatment / exposure:

Single IP injection (x2)

Frequency of treatment:

Twice: at 0hr and 24hr

Post exposure period:

30 hr

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 72, 108, 144 mg/kg
Basis:
no data

No. of animals per sex per dose:

4 mice per dose group (2 male/2 female)

Control animals:

yes, concurrent vehicle

Positive control(s):

no data

Examinations

Tissues and cell types examined:

bone marrow cells

Details of tissue and slide preparation:

CRITERIA FOR DOSE SELECTION: Based on preliminary toxicity study and LD50.
TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): Sampling time: 30 hrs post-treatment
DETAILS OF SLIDE PREPARATION: Femoral marrow cells were flushed were flushed out with foetal bovine serum and smeared onto clean glass slides. Cells were fixed with methanol for 5 min and stained with Acridine orange for the pilot experiment and with giemsa for the full-scale test.
METHOD OF ANALYSIS: 1000 polychromatic erythrocytes per mouse were scored using a light microscope and the number of micronucleated polychromatic erythrocytes (MNPCE's) was recorded (number of micronucleated cells not the number of micro nuclei).

Evaluation criteria:

A positive result was recorded only when one (or more) treatment group(s) showed a statistically significant difference (P<0.01) from the spontaneous level of MNPCE's and the trend test indicated a positive dose response (P<0.05)

Statistics:

Significance was calculated according to the Kastenbaum-Bowman tables.

Results and discussion

Test results

Sex:

male/female

Genotoxicity:

negative

Toxicity:

no effects

Remarks:

Dose levels determined on the basis of LD50. No mortality.

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

RESULTS OF RANGE-FINDING STUDY
No data on the parameters of range-finding study are reported, however the substance is reported as being negative in the pilot test.


RESULTS OF DEFINITIVE STUDY
- Ratio of PCE/NCE (for Micronucleus assay): no data
- Appropriateness of dose levels and route: dose levels determined on the basis of LD50

Any other information on results incl. tables

Table 1 - Results of an in vivo mouse micronucleus study with sodium monofluorophosphate

Compound	Surviving / Treated mice	Dose		Route of application	Micronucleated PE^a(%)
		mg/kg	mmole/kg
Sodium Monofluorophosphate	4/4	2 x 144	2 x 1.00	i.p.	3.2
	4/4	2 x 108	2 x 0.75	i.p.	2.9
	4/4	2 x 72	2 x 0.50	i.p.	2.2
	4/4	0	0	i.p.	2.0

 ^apolychromatic erythrocytes

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Under the conditions of the study, sodium monofluorophosphate is considered to be non-mutagenic.

This study is conducted according to an appropriate guideline and is therefore considered to be acceptable and to adequately satisfy both the guideline requirement and the regulatory requirement as a key study for this endpoint.