hexasodium (R)-carboxy(phosphono)methanolate (S)-carboxy(phosphono)methanolate

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Remarks:

Type of genotoxicity: gene mutation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: conducted to OECD/EC guidelines with GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

GLP compliance:

yes (incl. QA statement)

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): Trisodium [carboxy(oxido)methyl]phosphonate
- Substance type: Powder
- Physical state: Solid
- Lot/batch No.: LIC 613/04
- Storage condition of test material: Room temperature in the dark

Method

Species / strain

Species / strain 1

Species / strain / cell type:

E. coli WP2 uvr A

Species / strain 2

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Metabolic activation system:

S9 from livers of Sprague-Dawley rats

Test concentrations with justification for top dose:

50, 150, 500, 1500, 5000 micrograms/plate. (In the second repeat experiment, the doses used were the same except for the WP2uvrA- strain which was allocated an amended dose range of 150, 500, 1500, 3000 and 5000 micrograms/plate. The 3000 microgram/plate was introduced to confirm a better dose-response relationship and reproducibility as there were small increases in revertant colony frequency seen in experiment 1).

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: water
- Justification for choice of solvent/vehicle: Trisodium [carboxy(oxido)methyl]phosphonate was fully soluble in sterile distilled water at 50 mg/mL in solubility checks performed in house. Sterile distilled water was therefore selected as the vehicle.

Controls

Controls 1

Untreated negative controls:

yes

Remarks:

spontaneous mutation

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Controls 2

Positive controls:

yes

Positive control substance:

9-aminoacridine

Controls 3

Positive controls:

yes

Positive control substance:

4-nitroquinoline-N-oxide

Controls 4

Positive controls:

yes

Positive control substance:

other: 2-Aminoanthracene

Controls 5

Positive controls:

yes

Positive control substance:

benzo(a)pyrene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hours

NUMBER OF REPLICATIONS: 3 replicates/dose/strain

Evaluation criteria:

There are several criteria for determining a positive result, such as dose-related increase in revertant frequency over the dose range tested and/or a reproducible increase at one or more concentrations in at least one bacterial strain with or without metabolic activation.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

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

Test results 2

Species / strain:

E. coli WP2 uvr A

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:

In the first experiment, there was a small statistically significant increase in revertant colony frequency seen in the WP2uvr2- strain, without S9, at 5000 micrograms/plate. This response was not considered to be toxicologically significant as it was non-reproducible.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative

Trisodium [carboxy(oxido)methyl]phosphonate is considered to be non-mutagenic.

Executive summary:

In a reverse gene mutation assay in bacteria, strains TA 1535, TA 1537, TA 98 and TA 100 of S. typhimurium and E. coli WP2 uvr A  were exposed to Trisodium [carboxy(oxido)methyl]phosphonate at concentrations of 50, 150, 500, 1500, 5000 micrograms/plate in the presence and absence of mammalian metabolic activation. (In the second repeat experiment, the doses used were the same except for the WP2uvrA- strain which was allocated an amended dose range of 150, 500, 1500, 3000 and 5000 micrograms/plate).

 

The positive controls induced the appropriate responses in the corresponding strains.  

This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.