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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:
from 22 feb 1988 to 20 june 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Appearance: white crystals
Ref: EXT 8810

Method

Species / strain
Species / strain / cell type:
other: TA98, TA100, TA1535, TA1537 and TA1538
Metabolic activation:
with and without
Metabolic activation system:
S9 from rat liver cells, induced with Aroclor 1254
Test concentrations with justification for top dose:
0, 10, 100, 500, 1000 and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: usually used in this type of test.
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: see details below
Details on test system and experimental conditions:
Positive controls:
- Without metabolic activation: Sodium azide (3 µg/plate) for TA100 and TA1535; 9-Aminoacridine for TA1537; 2-Nitrofluorene (0.5 µg/plate) for TA98 and TA1538.
- With metabolic activation: 2-Aminofluorene (5 µg/plate) for TA98 and TA1538.

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- incubation period: 48 hours at 37°C
- Exposure duration: 48 hours

NUMBER OF REPLICATES: 3
Evaluation criteria:
- in TA 98 and TA 100: a test article is considered as positive if it produce at least a 2-fold increase in the mean revertant per plate of at least one of these tester strains over the mean revertants per plate of the appropriate vehicle control.
This increase in the number of revertant must be accompanied by a dose response with increasing concentrations of the test article
- in TA 1535, TA 1537 and TA 1538: idem, but a 3-fold increase is required

Results and discussion

Test results
Species / strain:
other: TA98, TA100, TA1535, TA1537 and TA1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
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

Tables of results (2 studies):

 

 

TA 98

TA 100

TA 1535

Conc.

[unit]

-S9

+S9

Cytotoxic

ity

-S9

+S9

Cytotoxic

ity

-S9

+S9

Cytotoxic

ity

0*

25/21

28/28

no

94/94

92

no

15/22

11/14

no

10

25/20

29/28

no

95/85

87

no

13/14

12/10

no

100

20/19

34/27

no

96/98

85

no

21/18

13/15

no

500

18/19

28/32

no

105/96

84

no

18/18

15/12

no

1000

20/24

21/33

no

98/95

93

no

18/27

9/17

no

5000

14/14

10/1/

no

84/83

79

no

15/25

8/9

no

Positive control

182/216

2012/1556

no

1036/889

/

no

938/697

/

 

no

 

 

TA 1537

TA 1538

Conc.

[unit]

-S9

+S9

Cytotoxic

ity

-S9

+S9

Cytotoxic

ity

0*

6/7

7/6

no

10/12

22/21

no

10

7/7

7/6

no

11/11

28/22

no

100

7/5

8/5

no

14/13

25/25

no

500

9/6

7/9

no

8/9

21/24

no

1000

6/6

9/8

no

13/14

21/24

no

5000

7/6

7/4

no

14/13

22/17

no

Positive control

1419/1563

/

no

283/239

1947/1435

no

*solvent control with DMSO

Applicant's summary and conclusion

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

Negative in Ames test, with and without metabolic activation.
Executive summary:

In a reverse gene mutation assay in bacteria (Hoechst, 1988), strains TA98, TA 100, TA 1535, TA 1537 and TA 1538 of S. typhimurium were exposed to Paradimethoxybenzene (purity unknown), in DMSO at concentrations of 0, 10, 100, 500, 1000 and 5000 µg/plate in the presence and absence of mammalian metabolic activation (plate incorporation method).

Paradimethoxybenzene was tested up to the limit concentration (5000 µg/plate). It was not mutagenic in Ames test.

The positive controls induced the appropriate responses in the corresponding strains. There was no evidence of induced mutant colonies over background.

This study is classified as acceptable. This study satisfies the requirement for Test Guideline OECD 471 for in vitro mutagenicity (bacterial reverse gene mutation) data.