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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study and Test procedure was in accordance with generally accepted scientific standards and described in sufficient details.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Robust summary for 1,5,9-cyclododecatriene (revised).
Author:
DuPont Safety, Health & Environmental Excellence Center, Wilmington (Del., USA)
Year:
2003
Bibliographic source:
U.S. EPA, 46 pp
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The test substance was evaluated for mutagenic activity with and without exogenous metabolic (S9) activation. Three replicates were plated for each tester strain, test concentration, and condition. Dimethyl sulfoxide (DMSO) was used as the solvent and negative control.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
1,5,9-cyclododecatriene
IUPAC Name:
1,5,9-cyclododecatriene
Details on test material:
1,5,9-cyclododecatriene, purity 100%

Method

Target gene:
Operon His
Species / strain
Species / strain / cell type:
other: Salmonella typhimurium TA97a, TA98, TA100, TA1535; E. coli strain WP2 uvrA (pKM101)
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
0; 10; 50; 100; 500; 1000; 2500; 5000 ug/plate
Vehicle / solvent:
dimethyl sulfoxide (DMSO)
Controls
Untreated negative controls:
yes
Remarks:
solvent (vehicle) DMSO
Negative solvent / vehicle controls:
yes
Remarks:
DMSO (see "Negative control")
True negative controls:
no
Positive controls:
yes
Remarks:
2-aminoanthracene, 2-nitrofluorene, sodium azide, ICR 191  acridine, methyl methanesulfonate; solvent DMSO except last three  positive controls: deionized water
Positive control substance:
other: 2-aminoanthracene, 2-nitrofluorene, sodium azide, ICR 191  acridine, methyl methanesulfonate; solvent DMSO except last three  positive controls: deionized water
Details on test system and experimental conditions:
SYSTEM OF TESTING
- Metabolic activation system:   arochlor induced rat liver S9 mix ADMINISTRATION: 
Treatments with exogenous metabolic activation were conducted by adding 0.1 mL of negative control or test substance solution, 0.5 mL of S9 mix, and 0.1 mL of an overnight culture containing at least 1 x 108 bacteria to 2 mL agar. These components were mixed and poured onto a plate containing approximately 25 mL of Davis minimal agar with dextrose (minimum agar plates). Treatments without activation were identical to those with activation, with the exception that the S9 mix was replaced with 0.5 mL of sterile phosphate buffered saline. Revertant colonies were counted after the individually labeled plates were incubated at approximately 37ºC for about 48 hours. When necessary, plates were refrigerated at approximately 2-4°C prior to counting.
- Number of replicates: 3
- Application: solvent dimethyl sulfoxide
- Positive and negative control groups and treatment:    positive: 2-aminoanthracene, 2-nitrofluorene, sodium azide, ICR 191  acridine, methyl methanesulfonate; solvent DMSO except last three  positive controls: deionized water; negative: DMSO (solvent)

-further details: see reference
Evaluation criteria:
number of revertants in any strain at any test substance concentration studied was at least 2 times greater than the average number of revertants in the negative control, and there was a positive dose-response relationship in that same strain. A test substance was classified as negative when there were no test substance concentrations with an average number of revertants that was at least 2 times greater than the average number of revertants in the negative control and there was no positive dose-response relationship.
Statistics:
No. For each tester strain, the average number of revertants and the standard deviation at each concentration with and without S9 activation were calculated.

Results and discussion

Test results
Species / strain:
other: Salmonella typhimurium TA97a, TA98, TA100, TA1535; E. coli strain WP2 uvrA (pKM101)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: not reported
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'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

In this Ames test, no evidence of mutagenic acitivity was detected with or without metabolic activation.
Executive summary:

The test substance was evaluated for mutagenic activity with and without exogenous metabolic (S9) activation. Three replicates were plated for each tester strain, test concentration, and condition. Dimethyl sulfoxide (DMSO) was used as the solvent and negative control. Four Salmonella typhimurium strains (TA97a, TA98, TA100, TA1535) and E. coli strain WP2 uvrA (pKM101) were used in this test, and the tested concentrations were 0; 10; 50; 100; 500; 1000; 2500; 5000 ug/plate.

There was no evidence of mutagenic acitivity was detected with or without metabolic activation in this Ames Test.

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