2,2-dimethylpropan-1-ol, tribromo derivative; 3-bromo-2,2-bis(bromomethyl)propan-1-ol

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

Study period:

1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and appropriate guidelines

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: US EPA Method: HG-GENE Muta-S. typhimurium: The salmonella typhimurium revers mutation assay 1984

Principles of method if other than guideline:

not relevant

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

2,2-dimethylpropan-1-ol, tribromo derivative

EC Number:

253-057-0

EC Name:

2,2-dimethylpropan-1-ol, tribromo derivative

Cas Number:

36483-57-5

Molecular formula:

C5H9Br3O

IUPAC Name:

3-bromo-2,2-bis(bromomethyl)propan-1-ol

Details on test material:

Identity: FR-513
Appearance: Off-white, flaky solid
Storage: Room temperature in the dark
Purity: 98%
Stable for at least two years

Method

Target gene:

histidine

Species / strain

Species / strain / cell type:

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

Details on mammalian cell type (if applicable):

not relevant

Additional strain / cell type characteristics:

other: Strains TA98 and TA1537 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:

liver preparation from Aroclor 1254-induced rats (uninduced syrian hamsters) rats and unindiced

Test concentrations with justification for top dose:

Concentration range in Preliminary toxicity determination (with/ without metabolic activation): 0, 5, 50, 500, 5000 µg/plate
Concentration range in the main test (with/without metabolic activation): solvent, 0, 15, 50, 150, 500, 1500 µg/plate

Vehicle / solvent:

Solvent: DMSO

Controls

Untreated negative controls:

yes

Remarks:

DMSO

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

yes

Remarks:

no test substance

Positive controls:

yes

Remarks:

N-Ethyl-N-nitro-N-nitrosoguanidine, 9-Amonoacridine, 2 Nitrofluorene, 2-Aminoantracene, Congo red

Details on test system and experimental conditions:

see attached document on experimental procedure

Evaluation criteria:

See attached document on assessment of results

Statistics:

no

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

Remarks:

5-500 µg/plate

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

5000 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

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

Metabolic activation:

without

Genotoxicity:

negative

Remarks:

0-500 µg/plate

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

1500µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

Species / strain:

S. typhimurium TA 1535

Metabolic activation:

with

Genotoxicity:

ambiguous

Remarks:

positive only in the presence of hamster S-9 mix (15-500 µg/plate)

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

1500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with

Genotoxicity:

ambiguous

Remarks:

positive only in the presence of hamster S-9 mix (15-500 µg/plate)

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

1500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 5

Species / strain:

S. typhimurium, other: TA 98, TA 1537

Metabolic activation:

with

Genotoxicity:

negative

Remarks:

15-500 µg/plate

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

1500 µg/plate

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Preliminary test: FR-513 was toxic towards all tester strains at 5000 µg/plate. Therefore, 1500 µg/plate was chosen at the top dose level in the mutation test.
Main tests: Following treatment with FR-513, large, dose-related increases in revertant colony numbers were observed in both mutation tests with
strains TA 1535 and TA 100. These increases were observed only in the presence of hamster S-9 mix and were largest in the present of the 30% mix.
The concurrent positive control compounds demonstrated the sensitivity of the assay and the metabolising activity of the liver preparations.

Remarks on result:

other: other: preliminary toxicity test

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

See attached document on tables

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information):
ambiguous with metabolic activation

It concluded that when tested in dimethyl sulphoxide, FR-513 shows no evidence of mutagenic activity in the absence or presence of rat S-9 mix.
FR-513 shows clear evidence of mutagenic activity between 500 and 15 µg/plate with strains TA 1535 and TA 100 in the presence of hamster S-9 mix.

Executive summary:

In vitro assesment of mutagenic potential of FR-513, histidine dependant auxtrophic mutants of S. typhimurium (Strains TA 1535, TA 1537, TA 98 and TA 100) was conducted according to the appropriate OECD guidelines such as OECD 471. Two independant mutation tests were conducted in the presence and absence of liver preparations from rats and hamsters.

It was concluded that when tested in dimethyl sulphoxide, FR-513 shows no evidence of mutagenic activity in the absence or presence of rat S-9 mix. FR-513 shows clear evidence of mutagenic activity between 500 and 15 µg/plate with strains TA 1535 and TA 100 in the presence of hamster S-9 mix.