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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not specified
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
read-across: supporting information
Reference
Endpoint:
genetic toxicity in vivo, other
Remarks:
Dominant Lethal Assay and In Vivo Micronucleus Test
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
See read-across justification in IUCLID Section 13
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
not applicable
Remarks on result:
other: OECD 478
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
not applicable
Negative controls validity:
valid
Positive controls validity:
valid
Remarks on result:
other: OECD 474

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:
no
Remarks:
pre-GLP
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
EC Number:
701-238-4
Molecular formula:
HEDP-2Na C2H6Na2O7P2 HEDP-3Na C2H5Na3O7P2
IUPAC Name:
Sodium Salts of (1-Hydroxyethylidene)bisphosphonic acid (2-3 Na:1)
Test material form:
not specified

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 / concentrationsopen allclose all
Dose / conc.:
18.75 mg/kg bw/day (nominal)
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:
In an in vivo mouse micronucleus assay, conducted to a protocol similar to OECD Test Guideline 474 and pre-GLP, HEDP (2-3Na) did not cause any increase in the number of PCEs detected after ip administration. Appropriate controls were included and gave expected result. It is concluded that HEDP (2-3Na) is negative for induction of micronuclei under the conditions of the test.