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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

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:
04 July 2002 - 21 February 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to OECD, EU, US FDA and Japanese (EPA, MHLW and METI) test guidelines, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.13/14 (Mutagenicity - Reverse Mutation Test Using Bacteria)
Version / remarks:
(Commission Directive 2000/32/EC; L136, 57-64, Annex 4D)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: US FDA Administration Center for Food Safey & Applied Nutrition Office of Premarket Approval, Redbook 2000, Toxicological Principles for the Safety of Food Ingredients, IV.C.1.a Bacterial Reverse Mutation Test, July 07, 2000.
Deviations:
no
Qualifier:
according to guideline
Guideline:
JAPAN: Guidelines for Screening Mutagenicity Testing Of Chemicals
Version / remarks:
"Kanpoan 287 - EPA", "Eisei 127 - MHLW", and "Heisei 09/10/31 Kikyoku 2 - METI"
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
(1R,2S,10R,11S)-tetracyclo[9.2.1.0²,¹⁰.0³,⁸]tetradeca-3(8),4,6,12-tetraene
EC Number:
700-736-9
Cas Number:
2149571-40-2
Molecular formula:
C14H14
IUPAC Name:
(1R,2S,10R,11S)-tetracyclo[9.2.1.0²,¹⁰.0³,⁸]tetradeca-3(8),4,6,12-tetraene
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): MTF
- Substance type: organic
- Physical state: liquid
- Analytical purity: 99.1%
- Lot/batch No.: 010920
- Stability under test conditions: > 3 days in water
- Storage condition of test material: Approx. 4°C. The container has to be tightly sealed with nitrogen. Each time, the test item is used, the container has to be refilled with nitrogen.

Method

Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
S. typhimurium TA 102
Species / strain / cell type:
E. coli WP2 uvr A
Metabolic activation:
with and without
Metabolic activation system:
rat-liver post mitochondrial supernatant (S9 fraction)
Test concentrations with justification for top dose:
Range finding test:
strains S. typhimurium TA 100 and E. coli WP2 uvrA (with and without methabolic activation): 20.6, 61.8, 185.2, 555.6, 1666.7 and 5000 µg/plate


without metabolic activation:
strains TA 100, TA 102: 1.0, 3.3, 10, 33 and 100 µg/plate
strain TA 1537: 10, 33, 100, 333 and 1000 µg/plate
strains TA 1535, TA 98, WP2 uvrA: 33, 100, 333, 1000 and 2500 µg/plate

with metabolic activation (pre-incubation assay):
strains TA 100, TA 1537, TA 102: 10, 33, 100, 333 and 1000 µg/plate
strains TA 1535, TA 98, WP2 uvrA: 33, 100, 333, 1000 and 2500 µg/plate

Due to a wide range of toxicity in the pre-incubation assay with microsomal activation, additional concentrations were tested with metabolic activation:
strains TA 100, TA 1537: 0.3, 1.0, 3.3, 10 and 33 µg/plate
strains T A 1535, T A 98, T A 102: 3.3, 10, 33, 100 and 333 µg/plate.
Controlsopen allclose all
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
Without metabolic activation
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
Without metabolic activation
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Without metabolic activation
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
4-nitroquinoline-N-oxide
Remarks:
Without metabolic activation
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
Without metabolic activation
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
cyclophosphamide
Remarks:
With metabolic activation
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
Positive controls:
yes
Positive control substance:
other: 2-AA
Remarks:
With metabolic activation

Results and discussion

Test resultsopen allclose all
Key result
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:
no cytotoxicity, but tested up to precipitating concentrations
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Positive controls validity:
valid
Key result
Species / strain:
E. coli WP2 uvr A
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity, but tested up to precipitating concentrations
Positive controls validity:
valid

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

During the described mutagenicity test and under the experimental conditions reported, the test item did not induced gene mutations by base-pair changes or frameshifts in the genome of the strains used.


Therefore, MTF is considered to be non-mutagenic in this Salmonella typhimurium and Escherichia coli reverse mutation assay.