Etidronic acid

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Ames Test

Principles of method if other than guideline:

The test was performed according to Ames et al. (Mutation Research 31 (1975) 347-364), Methods for detecting carcinogens and mutagens wlth the salmonella/mammalian microsome mutagenicity test. Guideline was not available at the time the test was performed.

GLP compliance:

no

Remarks:

Conducted prior to adoption of GLP

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium hydrogen (1-hydroxyethylidene)bisphosphonate

EC Number:

220-200-3

EC Name:

Trisodium hydrogen (1-hydroxyethylidene)bisphosphonate

Cas Number:

2666-14-0

Molecular formula:

C2H5O7P2.3Na

IUPAC Name:

trisodium hydrogen (1-hydroxyethane-1,1-diyl)bis(phosphonate)

Test material form:

not specified

Method

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with and without

Metabolic activation system:

Aroclor-induced and Phenbarbitol-induced rat liver S9

Test concentrations with justification for top dose:

Test substance: 2.7 / 27 / 270 / 2700 µg/plate
Positive controls: 67.5 µg/plate (o-nitro-p-phenylendiamin, 270 µg/plate (p-toluol-sulfonic acid hydrazide)
Solvent controls: 100 µl H2O + 100 µl acetone or 100 µl H2O + 100 µl DMSO, resp.
Untreated controls

Vehicle / solvent:

Water/acetone or water/DMSO, resp.

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water/acetone or water/DMSO, resp.

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: o-Nitro-p-phenylendiamine

Remarks:

Strains TA 1537, TA 1538, TA 98

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Remarks:

water/acetone or water/DMSO, resp.

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: p-toluolsulfonamidehydrazide

Remarks:

TA 100 and TA 1535

Evaluation criteria:

A substance is considered positive if at least one of the tested concentrations results in 2.5-times increase in the number of visible colonies relative to the solvent control in at least one test strains.

Results and discussion

Test results

Key result

Species / strain:

S. typhimurium, other: TA 98, TA 100, TA 1535, TA 1537, TA 1538

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Activity of Aroclor induced S9 was confirmed by testing TA 98 with Benzo-a-pyrene: 580 back mutations were induced. TA 100 induced 720 back mutations with 2-anthramine

Applicant's summary and conclusion

Conclusions:

HEDP-2Na has been tested for reverse mutation in bacteria, using a method that is similar to OECD 471. No evidence for mutagenicity was obtained under the conditions of the study up to 2700 µg/plate.