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Toxicological information

Genetic toxicity: in vitro

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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: EC B.14 study under GLCP, but study protocol dates back to 1992 (no E. coli strains included)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Natriummethallysulfonat
- Substance type: organic
- Physical state: solid
- Analytical purity: 99.8
- Impurities (identity and concentrations): not identified
- Composition of test material, percentage of components: pure
- Isomers composition: not appliacble
- Purity test date: 23-0601992
- Lot/batch No.: Ch 92/0650
- Expiration date of the lot/batch: indefinite
- Stability under test conditions: stable
- Storage condition of test material: no specific conditions

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 1538
Metabolic activation:
with and without
Metabolic activation system:
phenobarbital-induced liver microsomes
Test concentrations with justification for top dose:
0, 40, 200, 1000. 5000 microgr/plate
Vehicle / solvent:
water
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
fotr TA 98 and TA 1583
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
for TA 100 and 1535
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
for TA 1537
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
for TA100
Details on test system and experimental conditions:
pre-icubation test with and without S9 mix, 30 minuts at 30 degr C
Main test with and without S9-mix, incubation time 96 minutes at 37 degr. C ; three plates per concentration; independent repeat
Evaluation criteria:
any statistically significant increase in mutation frequency
Statistics:
not specified

Results and discussion

Test resultsopen allclose all
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:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

main test:

 

Mutation frequency quotient (relative to vehicle control)

 

TA98

TA100

TA1538

TA1537

 TA1538

Dose µgr/plate

S9 -

S9 +

S9 -

S9 +

S9 -

S9 +

S9 -

S9 +

S9 -

S9 +

Water

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

8

0.9

1.3

0.9

0.9

1.1

0.9

1.5

1.1

0.8

1.0

40

1.1

1.2

0.9

1.1

1.0

1.1

1.5

1.1

1.0

1.0

300

1.0

1.3

1.0

1.1

0.8

1.1

1.1

1.1

1.0

1.2

1000

1.0

1.3

1.0

0.8

0.8

0.8

1.3

1.2

1.2

1.2

5000

1.0

1.3

1.0

1.0

0.9

1.0

0.8

1.1

1.1

1.2

Nitrofluorene

2.9

 

 

 

 

 

 

 

3.4

 

Sodium azide

 

 

4.0

 

36.8

 

 

 

 

 

cyclophosfamide

 

 

1.0

2.2

 

 

 

 

 

 

Aminoacridine

 

 

 

 

 

 

9.3

 

 

 

Independent repeat:

 

Mutation frequency quotient (relative to vehicle control)

 

TA98

TA100

TA1538

TA1537

TA1538

Dose µgr/plate

S9 -

S9 +

S9 -

S9 +

S9 -

S9 +

S9 -

S9 +

S9 -

S9 +

Water

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

1.0

8

1.0

0.9

1.0

0.9

0.9

1.0

0.9

1.0

1.1

1.0

40

 0.9

1.0

1.0

1.0

0.9

0.9

1.0

0.8

1.0

0.9

300

 1.0

0.9

0.9

1.0

1.2

1.1

1.0

0.6

1.1

0.9

1000

 1.1

1.1

1.0

1.0

0.9

0.7

0.8

0.8

1.0

1.1

5000

 0.8

0.8

1.0

1.0

1.1

0.9

1.3

1.3

1.0

1.1

Nitrofluorene

 2.3

 

 

 

 

 

 

 

2.6

 

Sodium azide

 

 

3.6

 

 

38.3

 

 

 

 

cyclophosfamide

 

 

1.1

2.7

 

 

 

 

 

 

Aminoacridine

 

 

 

 

 

 

4.1

 

 

 

Applicant's summary and conclusion

Conclusions:
Substance is not mutagenic in a bacterial reverse mutation assay in concentrations up to 5000 microgram per plate
Executive summary:

Substane was tested in a bacterial reverse mutatuin assy with strains TA 98, 100, 1535, 1537 and 1538, with and without phenobarbital-induced S9 mix, with the apprpriate positive controls per strain.

Substance is not mutagenic in this bacterial reverse mutation assay in concentrations up to 5000 microgram per plate