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:
weight of evidence
Reliability:
2 (reliable with restrictions)

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Salmonella Mutagenicity Tests V. Results from the Testing of 311 Chemicals
Author:
Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., and Mortelman, K.
Year:
1992
Bibliographic source:
Environ. Molec. Mutagen. Vol. 19 (Suppl 21) (1992) 2-141
Reference Type:
other: Authoritative data base
Title:
Study ID : 628879
Author:
NTP Database
Year:
2012
Bibliographic source:
NTP (National Toxicological Program)by Agency for Toxic Substances and Disease Registry; Division of Toxicology/Toxicology Information Branch, 1600 Clifton Road NE, E-29, Atlanta, Georgia 30333
Reference Type:
other: Authoritative data base
Title:
GCID : 59193
Author:
ACToR Database
Year:
2011
Bibliographic source:
ACToR (Aggregated Computational Toxicology Resource) : [ZEIGER,E, ANDERSON,B, HAWORTH,S, LAWLOR,T AND MORTELMANS,K; SALMONELLA MUTAGENICITY TESTS. V. RESULTS FROM THE TESTING OF 311 CHEMICALS; ENVIRON. MOL. MUTAGEN. 19(SUPPL.21):2-141, 1992]

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other:
Principles of method if other than guideline:
PREINCUBATION : In the standard protocol (preincubation) for conducting the Ames assay, a test tube containing a suspension of one strain of Salmonella typhimurium (or E. coli) plus S9 mix or plain buffer without S9, is incubated for 20 minutes at 37º C with the test chemical. Control cultures, with all the same ingredients except the test chemical, are also incubated. In addition, positive control cultures are prepared; these contain the particular bacterial tester strain under investigation, the various culture ingredients, and a known potent mutagen*. After 20 minutes, agar is added to the cultures and the contents of the tubes are thoroughly mixed and poured onto the surface of Petri dishes containing standard bacterial culture medium. The plates are incubated, and bacterial colonies that do not require an excess of supplemental histidine appear and grow. These colonies are comprised of bacteria that have undergone reverse mutation to restore function of the histidine-manufacturing gene. The number of colonies is usually counted after 2 days.
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Clioquinol
EC Number:
204-984-4
EC Name:
Clioquinol
Cas Number:
130-26-7
Molecular formula:
C9H5ClINO
IUPAC Name:
5-chloro-7-iodoquinolin-8-ol
Details on test material:
- Name of test material (as cited in study report): clioquinol
- Substance type: Organic
- Physical state: Solid

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 100
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1535
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 1537
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 97
Additional strain / cell type characteristics:
not specified
Species / strain / cell type:
S. typhimurium TA 98
Additional strain / cell type characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
with 10 % & 30 % HLI = induced male Syrian hamster liver S9 and 10% & 30 % RLI = induced male Sprague Dawley rat liver S9
Test concentrations with justification for top dose:
1-100 µg/Plate
Vehicle / solvent:
Dimethyl Sulfoxide
Controlsopen allclose all
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Dimethyl Sulfoxide
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
For strains tested with S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Dimethyl Sulfoxide
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
For strains TA100 and TA1535 tested in the absence of S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Dimethyl Sulfoxide
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
For strain TA97 and TA1537 tested in the absence of S9
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
Dimethyl Sulfoxide
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
For strain TA98 tested in the absence of S9
Details on test system and experimental conditions:
Test System : AMES SALMONELLA TYPHIMURIUM

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 97
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
not specified
Untreated negative controls validity:
not specified
Positive controls validity:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Strain: TA100

Dose

No Activation 
(Negative)

No Activation 
(Negative)

10% HLI 
(Negative)

30% HLI 
(Negative)

10% RLI 
(Negative)

30% RLI 
(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0     

153

18.5

136

3.8

134

4.2

174

3.4

140

11.2

168

4.2

 0.03  

149

10.7

142

4.6

 

 

 

 

 

 

 

 

 0.1   

139

13.3

142

10.4

 

 

 

 

 

 

 

 

 0.3   

147

4.4

129

11.5

 

 

 

 

144

11.9

165

9.2

1     

136

2.6

82

1.8

152

7.1

158

1.9

129

3.5

153

9.4

1.6   

120

8.5

 

 

 

 

 

 

 

 

 

 

3     

 

 

0s

0

147

3.9

181

12.9

126

7.2

155

6.9

10     

 

 

 

 

146

3.7

153

21.3

96

3.7

142

8.4

16     

 

 

 

 

 

 

 

 

 

 

118

7.8

33     

 

 

 

 

103

8.7

184

3.6

13

5.1

 

 

66     

 

 

 

 

 

 

172

8.6

 

 

 

 

100     

 

 

 

 

0s

0

 

 

 

 

 

 

Positive Control

439

15.8

412

8.4

835

37.2

545

10.8

602

17.8

842

33.8

 Strain: TA1535

Dose

No Activation 
(Negative)

No Activation 
(Negative)

10% HLI 
(Negative)

30% HLI 
(Negative)

10% RLI 
(Negative)

30% RLI 
(Negative)

Protocol

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

Preincubation

ug/Plate

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

Mean

± SEM

0     

24

2.2

39

1.5

18

1.8

9

2.3

18

3.4

19

2.6

 0.03  

33

2.3

28

2.6

 

 

 

 

 

 

 

 

 0.1   

22

1.2

31

1.9

 

 

 

 

 

 

 

 

 0.3   

24

2.7

31

3.2

 

 

 

 

16

2

20

1.9

1     

26

1.2

31

3

18

0.9

12

1

16

0.7

17

0.3

1.6   

29

4.6

 

 

 

 

 

 

 

 

 

 

3     

 

 

7

0.6

18

6.8

9

2.4

18

2.5

20

2.6

10     

 

 

 

 

17

0.3

10

1.9

11

2.4

13

2.1

16     

 

 

 

 

 

 

 

 

 

 

20

2.3

33     

 

 

 

 

14

2.6

8

0.3

6

1.3

 

 

66     

 

 

 

 

 

 

15

1.5

 

 

 

 

100     

 

 

 

 

11

3.8

 

 

 

 

 

 

Positive Control

370

9.4

418

49.7

201

6.9

403

13.1

110

7.3

96

2.6

S

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

In an Ames test , clioquinol , in dimethyl sulfoxide from doses 1-100 µg/Plate was not mutagenic in Salmonella typhimurium strains TA100,TA1535,TA1537,TA97 and TA98 with and without addition of S9 liver fractions from Aroclor induced hamsters. The same has been observed for rats as well.
Executive summary:

In an Ames test , clioquinol , in dimethyl sulfoxide from doses 1-100 µg/Plate was not mutagenic in Salmonella typhimurium strains TA100,TA1535,TA1537,TA97 and TA98 with and without addition of S9 liver fractions from Aroclor induced hamsters. The same has been observed for rats as well.