tris[3-bromo-2,2-bis(bromomethyl)propyl] phosphate

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: GLP and appropriate references

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: 84-1

Principles of method if other than guideline:

The materials, methods and procedures used in this assay are those described by:
1. Ames et al; Mutation Research 31: 347-364, 1975
2. Maron and Ames; Mutation Research 113: 173-215, 1983

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

413-060-1

EC Name:

-

Cas Number:

19186-97-1

Molecular formula:

C15 H24 O4 P Br9

IUPAC Name:

tris[3-bromo-2,2-bis(bromomethyl)propyl] phosphate

Constituent 2

Reference substance name:

4130601

IUPAC Name:

4130601

Details on test material:

PB-370
Lot No.: E7061-46
Solid
Storage conditions: Room temperature

Method

Target gene:

Histidine

Species / strain

Species / strain / cell type:

bacteria, other: Salmonella Typhimurium: TA1535, TA1537, TA1538, TA98, TA100

Details on mammalian cell type (if applicable):

not relevant

Additional strain / cell type characteristics:

other: Strains TA98, TA 1537 and TA1538 were capable of detecting frameshift mutagens, strains TA100 and TA1535 are capable of detecting base-pair substitution mutagens

Metabolic activation:

with and without

Metabolic activation system:

S-9 from Aroclor 1254 induced rat liver microsomes

Test concentrations with justification for top dose:

Concentration range in Preliminary toxicity determination (with/ without metabolic activation): (DMSO 100 microliter), 5, 16.7, 33, 50, 167, 333, 500, 1667, 3333, 5000 µg/plate
Concentration range in the main test (with metabolic activation): 50, 167, 500, 1667, 5000 µg/plate
Concentration range in the main test (without metabolic activation): 50, 167, 500, 1667, 5000 µg/plate

Vehicle / solvent:

Solvent: DMSO

Controls

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

yes

Remarks:

no test substance

Positive controls:

yes

Remarks:

2-aminoanthracene, 9-Aminoacridine, sodium azide, 2-Nitrofluorene

Details on test system and experimental conditions:

Concentration of the test substance resulting in precipitation: 500 µg/plate

Evaluation criteria:

For a test article to be considered positive, it must cause at least a doubling in the mean number of revertants per plate of at least one strain. This increase in the mean number of revertants per plate must be accompained by a dose response to increasing concentration of the test article. In those cases where the observed dose response increase in TA1573 revertants per plate is less than three-fold, the response must be reproducible.

Statistics:

All mutagenicity plating was done in triplicate. For each triplicate plating, an average and standard deviation were calculated.

Results and discussion

Test results

Species / strain:

other: Salmonella Typhimurium: TA1535, TA1537, TA1538, TA98, TA100

Metabolic activation:

with and without

Genotoxicity:

negative

Remarks:

(> 5000 µg/plate)

Cytotoxicity / choice of top concentrations:

no cytotoxicity

Remarks:

(> 5000 µg/plate)

Positive controls validity:

valid

Additional information on results:

Observations:
Heavy precipitate was observed at 5000microgram/plate. No toxicity
was observed at this dose based on reduction in spontaneous
revertants. Slight to moderate precipitate was observed at
500 microg/plate and 1667 microg/plate.

No toxicity was seen in background lawn was seen

Remarks on result:

other: other: preliminary toxicity determination

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

See attached document on results

See attached document on tables

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
negative with metabolic activation
negative without metabolic activation

PB-370 did not cause a positive response in any of the tester strains with or without metabolic activation by Aroclor induced rat liver microsomes.

Executive summary:

A Salmonella/mammalian-Microsome Mutagenicity Assay (Ames Test) was conducted
with PB-370, E7061-46. Live tester strains of Salmonella typhimurium: TA98,
TA100, TA1535, TA1537 and TA1538 were utilized. The assay was conducted in the
presence and absence of metabolic activation by Aroclor 1254 induced rat liver
microsomes. The test article was partially solubilized in DMSO PB-370, E7061-
46 was tested at five dose levels ranging from 50 to 5000 ug/plate. The dose
levels were based on a preliminary toxicity test. Two Independent assays were
performed. Results of the first experiment were negative. No significant
increases in revertants occurred in any of the strains. In the second
experiment, TA1535, in the presence of activation, demonstrated a 2.3 fold
increase at 5000 ug/plate and elevated numbers of tevertants at the lower doses.
To confirm this a third assay, with TA1535 only (+S9), was performed. Results
were negative; no increases in revertants were observed. Thus, the results of
the second assay are suspect. Under the conditions of this study, PB-370 did not
cause a positive response in any of the tester strains with or without metabolic
activation by Aroclor induced rat liver microsomes, and therefore, was not
mutagenic in the Ames Test.