1,4-bis[(vinyloxy)methyl]cyclohexane

Genetic toxicity: in vitro

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 guidline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals

Deviations:

no

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

1,4-bis[(vinyloxy)methyl]cyclohexane

EC Number:

413-370-7

EC Name:

1,4-bis[(vinyloxy)methyl]cyclohexane

Cas Number:

17351-75-6

Molecular formula:

C12 H20 O2

IUPAC Name:

(1r,4r)-1,4-bis[(ethenyloxy)methyl]cyclohexane; (1s,4s)-1,4-bis[(ethenyloxy)methyl]cyclohexane

Details on test material:

- Name of test material (as cited in study report): CHDMDVE
- Physical state: colorless liquid
- Analytical purity: > 99.5
- Impurities (identity and concentrations): cyclohexanedimethanol monovinyl ether < 0.1 %; cyclohexanedimethanol < 0 .1 %
- Lot/batch No.: 870 8400
- Storage condition of test material: below 25 °C

Method

Target gene:

Salmonella Typhimurium: (his-)
E. Coli: (Trp-)

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Metabolic activation:

with and without

Metabolic activation system:

s9-Mix

Test concentrations with justification for top dose:

Dose range finding test 1.22-5000 µg/plate
0.61 - 78.1 µg/plate (without S9-Mix)
2.44-625 µg/plate (with S9-Mix)

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility of the test substance

Controls

Controls 1

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

other: 2 amino anthracene

Remarks:

all tests with metabolic activation

Controls 2

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

sodium azide

Remarks:

TA 1535

Controls 3

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

9-aminoacridine

Remarks:

TA 1537

Controls 4

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

furylfuramide

Remarks:

TA98; TA 100

Controls 5

Untreated negative controls:

yes

Negative solvent / vehicle controls:

yes

Positive controls:

yes

Positive control substance:

N-ethyl-N-nitro-N-nitrosoguanidine

Remarks:

E. coli WP2uvrA

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation

DURATION
- Preincubation period: 20 min at 37°C
- incubation duration: 48 h at 37°C

NUMBER OF REPLICATIONS: 2

DETERMINATION OF CYTOTOXICITY
- Method: relative total growth

Evaluation criteria:

Positive results
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the result

Statistics:

Mean calculated in result tables. No further data.

Results and discussion

Test results

Test results 1

Species / strain:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Untreated negative controls validity:

valid

Positive controls validity:

valid

Additional information on results:

TEST-SPECIFIC CONFOUNDING FACTORS: not reported
RANGE-FINDING/SCREENING STUDIES: yes
COMPARISON WITH HISTORICAL CONTROL DATA: not reported
ADDITIONAL INFORMATION ON CYTOTOXICITY: pronounce cytotoxicity obseved

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.

Any other information on results incl. tables

Preincubation test without metabolic incubation (0.61 – 78.1 µg/plate)
Strain	Experiment	Replicates	maximum revertant factor	dose dependency	Assessment
TA 98	1	2	0.9	no	negative
	2	2	1.1	no	negative
TA 100	1	2	1.0	no	negative
	2	2	1.1	no	negative
TA 1535	1	2	1.3	no	negative
	2	2	1.1	no	negative
TA 1537	1	2	1.1	no	negative
	2	2	1.1	no	negative
WP2 uvr A	1	2	1.2	no	negative
	2	2	1.2	no	negative
Preincubation test with metabolic activation (2.44-625 µg/plate)
Strain	Experiment	Replicates	maximum revertant factor	dose dependency	Assessment
TA 98	1	2	1.0	no	negative
	2	2	1.0	no	negative
TA 100	1	2	1.0	no	negative
	2	2	1.0	no	negative
TA 1535	1	2	1.2	no	negative
	2	2	1.6	no	negative
TA 1537	1	2	0.8	no	negative
	2	2	1.3	no	negative
WP2 uvr A	1	2	1.2	no	negative
	2	2	1.4	no	negative

Applicant's summary and conclusion

Executive summary:

Mutagenicity of 1,4 -cyclohexane dimethanol divinyl ether was tested in a bacterial reverse mutation GLP study according to japanese guidelines for Screening Mutagenicity Testing Of Chemicals (valid without restriction). The Strains TA 98, TA100, TA1535, TA1537 and Ecoli WP2uvr were used. Due to cytotoxicity the test was performed in concentration range from 0.6 to 78 µg/plate witout S9 -Mix and 2.4 to 625 µg/plate with metabolic activation. Positive and solvent controls gave the expected results. No mutagenic activity of the test compound was found under the conditions of the test.