Clioquinol

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Clioquinol was found to be non-genotoxic.

Link to relevant study records

Reference

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)

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

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

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

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'.

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

Weight of evidence studies reviewed for Genetic toxicity from reliable sources having Klimish rating 2.

 

The summary of the results are presented below

 

Sr.No	Endpoint	Interpretation of results	Strain/Species	Sources
1	Gene Mutation	Negative with and without metabolic activation	S. typhimurium TA 100,TA 1535,TA 1537,TA 97,TA 98	Environ. Molec. Mutagen.
2	Chromosomal abberation	Negative without metabolic activation	Chinese hamster Lung (CHL)	SSS QSAR
3	Gene mutation	Negative without metabolic activation	S. typhimurium TA 100	SSS QSAR

 

By applying weight of evidence approach, it was concluded that the test substance clioquinol does not exhibit positive gene mutation effect as is the same case for chromosome abberation.

Justification for selection of genetic toxicity endpoint

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.The chromosome abberation is based on the prediction for in-vitro mammalian chromosome aberration test on Chinese hamster Lung (CHL) without S9 metabolic activation it was estimated that clioquinol does not exhibit positive chromosomal effect.

Justification for classification or non-classification

Clioquinol shows negative activity as is the case for chromosome abberation for the same substance.