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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:
1990-06-19 to 1990-07-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is in compliance with GLPs and an accepted concurrent guideline for reversion assays
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1990-06-19 to 1990-07-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it is in compliance with GLPs and an accepted concurrent guideline for reversion assays
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in Section 13.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay
Target gene:
Not applicable
Species / strain / cell type:
other: TA 1535, TA 1537, TA 1538, TA 98, and TA 100
Additional strain / cell type characteristics:
other: uvrB and rfa deficient
Metabolic activation:
with and without
Metabolic activation system:
± S9 from aroclor induced rat liver
Test concentrations with justification for top dose:
Range-finding preliminary toxicity test: 5, 50, 500, and 5000 µg/plate
Mutation test: 1.5, 5, 15, 50, 150, and 500 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Untreated negative controls:
yes
Remarks:
DMSO
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 9-aminoacridine; n-ethyl-n'-nitro-n nitrosoguanidine; 2-nitrofluorene; 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: In agar (plate incorporation)


DURATION
- Exposure duration: 3 days
- Expression time (cells in growth medium): 10 hours

NUMBER OF REPLICATIONS: 3
Evaluation criteria:
The test material is considered mutagenic if two independent treatments with any bacterial strain produce a two-fold increase in the number of revertant colonies over concurrent solvent controls, accompanied by some evidence of a positive dose-response relationship.

The test material is not considered mutagenic if treatment at any dose level with any bacterial strain does not result in reproducible increases of revertant colonies (1.5 times) over the concurrent solvent controls
Statistics:
Statistical methods were not employed in the study .
Species / strain:
other: TA 1535, TA 1537, TA 1538, TA 98, and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
PRELIMINARY RANGE-FINDING/SCREENING STUDIES: 1-hexene when tested at 5000 µg/plate was found to be toxic to the S. typhimurium strains. Hence the 500 µg/plate dose was the highest dose tested in the mutagenicity test.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

No significant effects were observed at any dose level, with or without metabolic activation.

Conclusions:
negative

1-Hexene is not mutagenic when tested with Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538, with or without metabolic activation.
Executive summary:

In a reverse gene mutation assay in bacteria, strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of S. typhimurium were exposed to 1-hexene in DMSO at concentrations of 1.5, 5, 15, 50, 150, or 500 µg/plate in the presence and absence of mammalian metabolic activation using the plate-incorporation method.

1 -Hexene was tested up to cytotoxic concentrations (5000 µg/plate) in a preliminary range-finding study and based on the results, the above mentioned concentrations were tested in the mutagenicity study. No substantial increases in revertant colony numbers of any of the five tester strains were observed subsequent to treatment with 1-hexene at any dose level, either in the presence or absence of metabolic activation.There was no evidence of induced mutant colonies over background or a concentration related positive response observed during the study. The positive controls induced the appropriate responses in the corresponding strains. 

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because it is in compliance with GLPs and an accepted concurrent guideline for reversion assays.

 

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1-Hexene
- Molecular formula (if other than submission substance): CH3CH2CH2CH2CH=CH2
- Substance type: C6 alpha olefin
- Physical state: Liquid
- Analytical purity: 99.06%
- Lot/batch No.: 300-892
- Expiration date of the lot/batch: 1995-05-30
- Stability under test conditions: Not determined
- Storage condition of test material: Room temperature in the dark under dry nitrogen
- Other: Stored in solvent dimethylsulphoxide

Method

Target gene:
Not applicable
Species / strain
Species / strain / cell type:
other: TA 1535, TA 1537, TA 1538, TA 98, and TA 100
Additional strain / cell type characteristics:
other: uvrB and rfa deficient
Metabolic activation:
with and without
Metabolic activation system:
± S9 from aroclor induced rat liver
Test concentrations with justification for top dose:
Range-finding preliminary toxicity test: 5, 50, 500, and 5000 µg/plate
Mutation test: 1.5, 5, 15, 50, 150, and 500 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
Controls
Untreated negative controls:
yes
Remarks:
DMSO
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
other: 9-aminoacridine; n-ethyl-n'-nitro-n nitrosoguanidine; 2-nitrofluorene; 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: In agar (plate incorporation)


DURATION
- Exposure duration: 3 days
- Expression time (cells in growth medium): 10 hours

NUMBER OF REPLICATIONS: 3
Evaluation criteria:
The test material is considered mutagenic if two independent treatments with any bacterial strain produce a two-fold increase in the number of revertant colonies over concurrent solvent controls, accompanied by some evidence of a positive dose-response relationship.

The test material is not considered mutagenic if treatment at any dose level with any bacterial strain does not result in reproducible increases of revertant colonies (1.5 times) over the concurrent solvent controls
Statistics:
Statistical methods were not employed in the study .

Results and discussion

Test results
Species / strain:
other: TA 1535, TA 1537, TA 1538, TA 98, and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not determined
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
PRELIMINARY RANGE-FINDING/SCREENING STUDIES: 1-hexene when tested at 5000 µg/plate was found to be toxic to the S. typhimurium strains. Hence the 500 µg/plate dose was the highest dose tested in the mutagenicity test.
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

No significant effects were observed at any dose level, with or without metabolic activation.

Applicant's summary and conclusion

Conclusions:
negative

1-Hexene is not mutagenic when tested with Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538, with or without metabolic activation.
Executive summary:

In a reverse gene mutation assay in bacteria, strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of S. typhimurium were exposed to 1-hexene in DMSO at concentrations of 1.5, 5, 15, 50, 150, or 500 µg/plate in the presence and absence of mammalian metabolic activation using the plate-incorporation method.

1 -Hexene was tested up to cytotoxic concentrations (5000 µg/plate) in a preliminary range-finding study and based on the results, the above mentioned concentrations were tested in the mutagenicity study. No substantial increases in revertant colony numbers of any of the five tester strains were observed subsequent to treatment with 1-hexene at any dose level, either in the presence or absence of metabolic activation.There was no evidence of induced mutant colonies over background or a concentration related positive response observed during the study. The positive controls induced the appropriate responses in the corresponding strains. 

 

This study received a Klimisch score of 1 and is classified as reliable without restriction because it is in compliance with GLPs and an accepted concurrent guideline for reversion assays.