Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (1-2:1)

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

Deviations:

yes

Remarks:

only 4 animals per sex per dose; only one sample of bone marrow; only 2 doses

Principles of method if other than guideline:

Method: Schmid W, Mutation Res, 31, (1975), 9-15.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Disodium dihydrogen (1-hydroxyethylidene)bisphosphonate

EC Number:

231-025-7

EC Name:

Disodium dihydrogen (1-hydroxyethylidene)bisphosphonate

Cas Number:

7414-83-7

Molecular formula:

C2H8O7P2.2Na

IUPAC Name:

disodium dihydrogen (1-hydroxyethane-1,1-diyl)bis(phosphonate)

Constituent 2

Reference substance name:

(1-hydroxyethylidene)bisphosphonic acid, disodium salt

IUPAC Name:

(1-hydroxyethylidene)bisphosphonic acid, disodium salt

Test material form:

not specified

Details on test material:

CAS No. 7414-83-7
Disodium ethane-1-hydroxy-1,1-diphosphonate, purity, source not stated.

Test animals

Species:

mouse

Strain:

CF-1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 9 weeks

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: no data

Duration of treatment / exposure:

Two intraperitoneal doses at 0 and 24 hours

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

18.75 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

150 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

four

Control animals:

yes, concurrent no treatment

Positive control(s):

- Endoxan
- Doses / concentrations: 120 mg/kg bw

Examinations

Tissues and cell types examined:

Femoral bone marrow

Results and discussion

Test results

Key result

Sex:

male/female

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Any other information on results incl. tables

Table 1: Mean Results of in vivo micronucleus test with mouse bone marrow

-	Negative Control	Negative Control	Positive Control (Endoxan)	Positive Control (Endoxan)	Low dose 18.75 mg/kg	Low dose 18.75 mg/kg	High dose 150 mg/kg	High dose 150 mg/kg
	male	female	male	female	male	female	male	female
Sampling time (h)	6	6	6	6	6	6	6	6
Number of cells analysed	1000	1000	1000	1000	1000	1000	1000	1000
Micronucleated cells per animal %	3	3.3	35	34	3	2.8	3.3	1.5
Ratio PCE/NCE	782	815	250	386	785	852	875	947

Applicant's summary and conclusion

Conclusions:

HEDP, disodium salt has been tested in a mouse micronucleus assay. No increase in the number of PCEs was detected after ip administration. It is concluded that the test substance is negative for induction of micronuclei under the conditions of the test.