Registration Dossier

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:
July 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline study report

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Isopropenyl acetate
EC Number:
203-562-7
EC Name:
Isopropenyl acetate
Cas Number:
108-22-5
Molecular formula:
C5H8O2
IUPAC Name:
isopropenyl acetate
Details on test material:
A c. 3 kg sample of the t est substance , a colourless liquid, designated Isopropenyl acetate ( CAS Reg. no. 108-22-5; purity 99.96%), was received
in two bottles (each containing c . 1.5 kg) from wacker Chemie GmbH, Munich, Germany on June 30, 1988. The test substance was stored at
ambient temperature, until use.

Method

Target gene:
not applicable
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
TA 98 His 03052 rfa uvrB +R
TA 100 His G46 rfa uvrB +R
TA 1537 His C3076 rfa uvrB -R
TA 1535 Hi s G46 rfa uvrB -R
Species / strain / cell type:
S. typhimurium TA 1538
Details on mammalian cell type (if applicable):
TA 1538 His 03052 rfa uvrB -R
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
1. and 2. experiment: 0.00, 1.23, 3.70, 11.11, 33.33, 100.00 mg per plate
Vehicle / solvent:
DMSO
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
with the strains TA 1535 and TA 100, in the absence of the S9 mix
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
with the strains TA 1538 and TA 98, in the absence of the S9 mix
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
with strain TA 1537, in the absence of the S9 mix
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene
Remarks:
with all strains in presence of S9
Details on test system and experimental conditions:
METHOD OF APPLICATION: plate-incorporation method


DURATION
- Preincubation period:
- Exposure duration:
- Expression time (cells in growth medium):
- Selection time (if incubation with a selection agent):
- Fixation time (start of exposure up to fixation or harvest of cells):


SELECTION AGENT (mutation assays):
SPINDLE INHIBITOR (cytogenetic assays):
STAIN (for cytogenetic assays):


NUMBER OF REPLICATIONS:


NUMBER OF CELLS EVALUATED:


DETERMINATION OF CYTOTOXICITY
- Method: mitotic index; cloning efficiency; relative total growth; other:


OTHER EXAMINATIONS:
- Determination of polyploidy:
- Determination of endoreplication:
- Other:


OTHER:
Evaluation criteria:
A positive response in the assay system is taken to be a two-fold or greater increase in the mean number of revertant colonies appearing in the test plates over and above the background spontaneous rever-sion rate observed with the vehicle, together with evidence of a dose-response.
Statistics:
not reported

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 / choice of top concentrations:
cytotoxicity
Remarks:
highest dose tested
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
highest dose tested
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
TEST-SPECIFIC CONFOUNDING FACTORS
- Effects of pH: not reported
- Effects of osmolality: not reported
- Evaporation from medium: not reported
- Water solubility: not reported
- Precipitation: not reported
- Other confounding effects: no


RANGE-FINDING/SCREENING STUDIES: yes


COMPARISON WITH HISTORICAL CONTROL DATA: yes

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

The substance did not induce shift mutations under the conditions used both in the absence and presence of S9.
Executive summary:

Isopropenyl acetate was examined for mutagenic activity in five strains of Salmonella typhimurium both in the -absence and in the presence of a metabolic activation system (S-9 mix), in compliance with OECD guideline 471 ("Salmonella typhimurium, Reverse Mutation Assay").From the results obtained in both experiments it appeared that incubation of the test substance with the bacteria did not increase the number of his+ revertants with S. typhimurium TA 1535, TA 1537, TA 1538, TA 98 or TA 100, either in the absence or in the presence of the S-9 mix. At the highest dose level used (100. 0 mg/plat e ) the test substance appeared to be (slightly) toxic for all strains, as was seen from a diminished background lawn of bacterial growth and/or a strong reduction of the number of his+ revertants as compared with the controls. The positive controls used in the present assays gave the expected strong increase in the number of his+ revertants, both in the absence and in the presence of the S-9 mix.

From the above findings it is concluded that Isopropenyl acetate did not show mutagenic activity in Salmonella typhimurium TA 1535 , TA 1537, TA 1538, TA 98 or TA 100 either in the absence or in the presence of the S-9 mix, under the conditions employed in this evaluation