Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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 16 dec 1990 to 09 may 1991
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study is sufficiently documented and the test conditions are similar to current test guidelines. The study was conducted according to GLP. The purity of the test substance is unknown.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Vanillin
EC Number:
204-465-2
EC Name:
Vanillin
Cas Number:
121-33-5
Molecular formula:
C8H8O3
IUPAC Name:
4-hydroxy-3-methoxybenzaldehyde

Method

Species / strain
Species / strain / cell type:
other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, TA1538
Metabolic activation:
with and without
Metabolic activation system:
S9 from induced Aroclor 1254
Test concentrations with justification for top dose:
100, 333, 667, 1000, 3330, and 5000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-nitrofluorene (1 µg/pl): in TA 98 and TA 1538 without S9 mix; sodium azide (2 µg/pl): in TA 100 and TA 1535 without S9 mix; ICR 191 (2 µg/pl): in TA 1537 without S9 mix; 2-aminoanthracene (2.5 µg/pl): in all strains with S9 mix
Details on test system and experimental conditions:
- Method of application: in agar (plate incorporation)
- Duration:
* Preincubation period: none
* Exposure duration: 48 +/- 8 hrs
- 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
Statistics:
no data

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium TA98, TA100, TA1535, TA1537, 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

 

TA 98

TA 100

TA 1535

Conc.
[unit]

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

14

22

no

94

120

no

17

14

no

100

14

22

no

97

115

no

13

14

no

333

9

27

no

92

111

no

12

6

no

667

10

26

no

79

106

no

10

12

no

1000

12

17

no

85

97

no

15

10

no

3330

13

17

no

65

80

no

10

13

no

5000

12

19

no

77

82

no

10

13

no

Positive control

209

998

no

602

1020

no

542

100

 

no

 

TA 1537

TA 1538

Conc.
[unit]

— MA

+ MA

Cytotoxic
(yes/no)

— MA

+ MA

Cytotoxic
(yes/no)

0*

4

6

no

13

17

no

100

7

9

no

18

13

no

333

4

9

no

11

16

no

667

8

7

no

12

16

no

1000

4

6

no

13

17

no

3330

7

5

no

13

13

no

5000

5

6

no

9

15

no

Positive control

194

118

no

243

1112

no

*solvent control with DMSO

Applicant's summary and conclusion

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

In a reverse gene mutation assay in bacteria (Lawlor, 1991), strains TA98, TA 100, TA 1535, TA 1537 and TA 1538 of S. typhimurium were exposed to Vanillin (purity unknown), in DMSO at concentrations of 100, 333, 667, 1000, 3330 and 5000 µg/plate in the presence and absence of mammalian metabolic activation (plate co-incubation method). Vanillin was tested up to the limit concentration (5000 µg/plate).

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 EU B.13/14 for in vitro mutagenicity (bacterial reverse gene mutation) data.