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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 guidline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Deviations:
no
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 / strainopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
s9-Mix
Species / strain:
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:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: solubility of the test substance
Controlsopen allclose all
Negative controls:
yes
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
other: 2 amino anthracene
Remarks:
all tests with metabolic activation
Negative controls:
yes
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
TA 1535
Negative controls:
yes
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
TA 1537
Negative controls:
yes
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
furylfuramide
Remarks:
TA98; TA 100
Negative controls:
yes
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
N-ethyl-N-nitro-N-nitrosoguanidine
Remarks:
E. coli WP2uvrA
Details on test system and 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 resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
yes
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
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

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.