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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: Comparable to guideline study but with restrictions (no GLP, only few details on experimental procedure, E. coli was not included to detect cross-linking, in experiments with metabolic activation a positive control was only investigated in TA1535)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979
Reference Type:
publication
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
(E.coli was not included, only few details on experimental procedure, in experiments with metabolic activation a positive control was only investigated in TA1535)
GLP compliance:
no
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): Tinuvin 328
- Batch No.: EN.2299

Method

Target gene:
his operon
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain / cell type characteristics:
other: histidine-auxotrophic
Metabolic activation:
with and without
Metabolic activation system:
S9 fraction of liver from rats induced with Aroclor 1254 and a solution of co-factors
Test concentrations with justification for top dose:
25, 75, 225, 675, 2025 µg/0.1 ml
Vehicle / solvent:
- solvent used: acetone
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: daunorubicin-HCl (5 & 10 µg/0.1ml phosphate buffer), 4-nitroquinoline-N-oxide (0.125 & 0.25 µg/0.1ml), N-methyl-N'-nitro-N-nitrosoguanidine (3 & 5 µg/0.1ml), 9(5)aminoacridine hydrochloride monohydrate (50 & 100 µg/0.1ml DMSO), no metabolic activation
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
with metbolic activation (only for TA 1535)

Migrated to IUCLID6: 250 µg/0.1 ml
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 h at 37 °C in darkness

NUMBER OF REPLICATIONS: 3 plates each concentration or control group
Evaluation criteria:
A test substance was generally considered to be non-mutagenic if the colony count in relation to the negative control is not doubled at any concentration.
Statistics:
When the colonies had been counted, the arithmetic mean was calculated.

Results and discussion

Test results
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 determined
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Precipitation: the concentrations 225, 675, and 2025 µg/0.1 ml precipitated in the soft agar
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Tab. 1 Salmonella/Mammalian-Microsome Mutagenicity Test: Experiments without microsomal activation (Number (arithmetic mean) of colonies of histidine-prototrophic back-mutants)

Results of the test substance

test substance concentration

TA 98

TA 100

TA 1535

TA 1537

control

30

235

9

6

25 µg/0.1 ml

38

226

14

6

75 µg/0.1 ml

26

248

20

9

225 µg/0.1 ml

33

249

16

5

675 µg/0.1 ml

34

248

21

7

2025 µg/0.1 ml

30

248

19

4

Tab. 2: Salmonella/Mammalian-Microsome Mutagenicity Test: Experiments without microsomal activation (Number (arithmetic mean) of colonies of histidine-prototrophic back-mutants)

Results of the positive controls

positive control

concentration

TA 98

TA 100

TA 1535

TA 1537

Daunorubicin-HCl

control

32

 

 

 

 

5.0 µg/0.1 ml

727

 

 

 

 

10.0 µg/0.1 ml

553

 

 

 

4-Nitroquinoline-N-oxide

 

control

 

 

259

 

 

 

0.125 µg/0.1 ml

 

662

 

 

 

0.25 µg/0.1 ml

 

>1100

 

 

N-Methyl-N'-nitro-

N-nitrosoguanidine

 

control

 

 

 

 

15

 

 

3 µg/0.1 ml

 

 

44

 

 

5 µg/0.1 ml

 

 

547

 

9(5)Aminoacridine

hydrochloride

 

control

 

 

 

 

6

 

50 µg/0.1 ml

 

 

 

39

 

100 µg/0.1 ml

 

 

 

388

Tab. 3 Salmonella/Mammalian-Microsome Mutagenicity Test: Experiments with microsomal activation (Number (arithmetic mean) of colonies of histidine-prototrophic back-mutants)

Results of the test substance

test substance concentration

TA 98

TA 100

TA 1535

TA 1537

control

42

201

18

17

25 µg/0.1 ml

32

209

15

13

75 µg/0.1 ml

31

195

18

16

225 µg/0.1 ml

31

207

14

17

675 µg/0.1 ml

43

203

20

13

2025 µg/0.1 ml

48

222

21

19

Tab. 4 Salmonella/Mammalian-Microsome Mutagenicity Test: Experiments with microsomal activation (Number (arithmetic mean) of colonies of histidine-prototrophic back-mutants)

Results of the positive control

positive control

concentration

TA 1535

Cyclophosphamide

control

22

 

250 µg/0.1 ml

584

Cyclophosphamide

control

10

 

250 µg/0.1 ml

206

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative