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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
Study period:
1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was performed in accordance with the OECD guideline 471 and the GLP standard.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2006

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not specified
Principles of method if other than guideline:
NA
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report):4,4'-Oxybis(benzenesulfonyl hydrazide)
- Analytical purity: no data
- Purity test date: > 99%
- Lot/batch No.: no data

Method

Target gene:
no data
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2
Details on mammalian cell type (if applicable):
NA
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
Male rat, liver, S9 mix induced with Aroclor 1254
Test concentrations with justification for top dose:
11.1, 33.3, 100, 300, 1,000, and 3,000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controls
Untreated negative controls:
yes
Remarks:
solvent
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
other: 4-nitroquinoline and 2-aminoanthracene
Details on test system and experimental conditions:
Description of follow up repeat study: Dose range finding experiment was carried out using dose levels with 5-fold intervals of 1.6, 8, 40, 200, 1,000, and 5,000 µg/plate both in the absence and in the presence of metabolic activation system.
Evaluation criteria:
The number of revertant colonies increased significantly in at least one strain at one or more concentrations or the data set showed a dose related correlation.
Statistics:
no data

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 98
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 3000 µg/plate
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Species / strain:
S. typhimurium TA 100
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 3000 µg/plate
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 3000 µg/plate
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
above 300 µg/plate
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity nor precipitates, but tested up to recommended limit concentrations
Additional information on results:
none

Any other information on results incl. tables

Table.Result of bacterial reverse mutation assay with4,4’-oxybis(benzenesulfonyl hydrazide)

Tester strain

Chemical treated

Dose (mg/plate)

Colonies/plate (mean±SD)

without S9 mix

with S9 mix

TA 98

Test item

    0

31±1

32±3

      11.1

20±6

29±3

     33.3

24±5

35±2

  100

34±3

40±6

  300

101±2

30±10

1,000

305±741

44±4

3,000

0±04

41±9

TA 100

Test item

    0

100±16

113±0

      11.1

189±83

169±16

     33.3

219±7

269±12

  100

315±13

439±18

  300

349±1

438±68

1,000

302±12

318±8

3,000

0±04

349±8

TA 1535

Test item

    0

10±0

8±4

      11.1

73±8

120±10

     33.3

118±3

295±13

  100

243±2

437±61

  300

187±20

320±61

1,000

12±32

259±15

3,000

0±04

449±47

TA 1537

Test item

    0

14±3

16±1

      11.1

24±2

13±4

     33.3

18±1

17±1

  100

12±6

17±0

  300

-   3

18±4

1,000

-   3

24±1

3,000

0±04

16±4

E. coli

WP2uvrA

Test item

    0

15±1

15±2

      11.1

12±1

21±1

     33.3

13±6

15±6

  100

22±4

13±1

  300

19±1

15±3

1,000

22±6

15±3

3,000

13±2

22±2

Positive control

TA 98

2-NF

    1.0

209±1

 

2-AA

    2.0

 

550±88

TA 100

SA

    0.5

502±62

 

2-AA

    2.0

 

699±13

TA 1535

SA

    0.5

251±24

 

2-AA

    5.0

 

131±9

TA 1537

9-AA

  50.0

355±8

 

2-AA

    5.0

 

259±39

WP2uvrA

4-NQ

    2.0

926±86

 

2-AA

10

 

297±115

1;Colony counting and slight thin lawn, some very slight toxicity                                                                   

2;Colony counting and thin lawn but microcolonies still evident

3;No colony count and thin lawn and probably macroscopic colonies grown from microcolonies

4;Complete killing

2-NF; 2-Nitrofluorene, 2-AA; 2-Aminoanthracene, SA; Sodium azide, 9-AA; 9-Aminoacridine, 4-NQ; 4-Nitroquinoline

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive

OBSH showed mutagenic effects in Salmonella typhimurium TA 98, TA 100, and TA 1535 without metabolic activation and in Salmonella typhimurium TA 100 and TA 1535 with metabolic activation system.
Executive summary:

The genetic toxicity in vitro of OBSH was evaluation in a bacterial reverse mutation assay. The study was performed in accordance with the OECD guideline 471. OBSH showed mutagenic effects in Salmonella typhimurium TA 98, TA 100, and TA 1535 without metabolic activation and in Salmonella typhimurium TA 100 and TA 1535 with metabolic activation system.