Radia 7838

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:

July 12 to August 2, 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study has been performed according to OECD guidelines and according to GLP principles

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Deviations:

yes

Remarks:

The temperature was above the protocolled range of 37.0 °C for approximately 60 minutes in the second mutation experiment (with a maximum of 38.6 °C). The study integrity was not adversely affected by the deviation.

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

The temperature was above the protocolled range of 37.0 °C for approximately 60 minutes in the second mutation experiment (with a maximum of 38.6 °C). The study integrity was not adversely affected by the deviation.

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

- Name of test material (as cited in study report): Radiagreen RA
- Physical state: Yellow to amber liquid
- Analytical purity: Unknown
- Lot/batch No.: OE70125
- Expiration date of the lot/batch: 25 January 2011
- Stability under test conditions: Stable
- Storage condition of test material: In refrigerator (2-8ºC) in the dark

Method

Target gene:

- S. typhimurium: Histidine gene
- E. coli: Tryptophan gene

Species / strain

Species / strain / cell type:

bacteria, other: Salmonella typhimurium (TA1535, TA1537, TA98 and TA100) and Escherichia coli (WP2uvrA).

Metabolic activation:

with and without

Metabolic activation system:

rat liver S9-mix induced by a combination of phenobarbital and ß-naphthoflavone

Test concentrations with justification for top dose:

Concentration range in the main test (with metabolic activation): 33, 100, 333, 1000 and 3330 µg/plate
Concentration range in the main test (without metabolic activation): 33, 100, 333, 1000 and 3330 µg/plate

Vehicle / solvent:

Solvent: Dimethyl sulfoxide

Controls

Controls 1

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

for TA1535

Positive control substance:

sodium azide

Remarks:

Migrated to IUCLID6: without S9-mix

Controls 2

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

for T1537

Positive control substance:

9-aminoacridine

Remarks:

Migrated to IUCLID6: without S9-mix

Controls 3

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

for TA98

Positive control substance:

2-nitrofluorene

Remarks:

Migrated to IUCLID6: without S9-mix

Controls 4

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

for TA100

Positive control substance:

methylmethanesulfonate

Remarks:

Migrated to IUCLID6: without S9-mix

Controls 5

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

for WP2uvrA

Positive control substance:

4-nitroquinoline-N-oxide

Remarks:

Migrated to IUCLID6: without S9-mix

Controls 6

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

Positive controls:

yes

Remarks:

for all strains with S9-mix

Positive control substance:

other: 2-Aminoanthracene

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Remarks:

(> 333 µg/plate)

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:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

from 1000 µg/plate and upwards

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 3

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:

cytotoxicity

Remarks:

(> 333 µg/plate)

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 4

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

no cytotoxicity, but tested up to precipitating concentrations

Remarks:

seen at 3330 µg/plate

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

Observations:
All bacterial strains showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in two independently repeated experiments. The negative and strain-specific positive control values were within our laboratory historical control data ranges indicating that the test conditions were adequate and that the metabolic activation system functioned properly.

Remarks on result:

other: other: preliminary test

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Comments:
The negative and strain-specific positive control values
were within our laboratory historical control data ranges
indicating that the test conditions were adequate and that
the metabolic activation system functioned properly.

Applicant's summary and conclusion

Conclusions:

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

All bacterial strains showed negative responses over the entire dose range, i.e. no significant dose-related increase in the number of revertants in two independently repeated experiments.