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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
plates not replicated, range of strains not compliant with current guideline
Principles of method if other than guideline:
Methods for detecting carcinogens and mutagens with Salmonella mammalian-microsome mutagenicity test. Mutation Res. 31, 347-364. 1975.
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Chemical structure
Reference substance name:
Hexamethylcyclotrisiloxane
EC Number:
208-765-4
EC Name:
Hexamethylcyclotrisiloxane
Cas Number:
541-05-9
Molecular formula:
C6H18O3Si3
IUPAC Name:
hexamethyl-1,3,5,2,4,6-trioxatrisilinane

Method

Species / strain
Species / strain / cell type:
S. typhimurium, other: TA-1535, TA-1537, TA-1538, TA-98, TA-100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
0.1, 1.0, 10 and 500 µg/plate
Vehicle / solvent:
ethanol
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 1-nitrosoguanidine
Remarks:
TA1535 and TA100 without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: quinacrine mustard
Remarks:
TA1537 without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
TA98 and TA1538 without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: anthraquinone
Remarks:
TA100 and TA1535 with activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: aminoquinoline
Remarks:
TA1537 with activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
ethanol
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: acetyl aminofluorene
Remarks:
TA1538 and TA98 with activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium; in agar (plate incorporation);

DURATION
- Exposure duration: 48 hours
- Expression time (cells in growth medium): 48 hours

NUMBER OF REPLICATIONS: no replicates

DETERMINATION OF CYTOTOXICITY
- Method: no information
Evaluation criteria:
A substance producing a positive dose response over three concentrations, with lowest increase equal to twice the solvent control (TA1535, 1537, 1538) or the highest increase at least twice (TA 100) or 2-3 times (TA 98) is considered positive

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 500 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 500 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 500 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 500 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
other: 500 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
All positive controls produced significantly increased revertants, while the negative controls did not.
No testing strains increased the number of revertants relative to the negative controls when tested with and without metabolic activation.  The maximum number of revertants in the solvent control was 230 (TA 100) and in the treated cultures was 292. The positive control gave a maximum of >1000 revertants (TA 1535)

Applicant's summary and conclusion

Conclusions:
Hexamethylcyclotrisiloxane has been tested for mutagenicity to bacteria in a valid in vitro study in S. typhimurium TA1535, TA1537, TA1538, TA98, TA100, conducted according to a protocol similar to OECD Test Guideline 471 but prior to GLP compliance. The test material did not increase the number of revertants in any of the strains tested in a valid, reliable and reproducible study when tested with or without metabolic activation up to a limit concentration. Positive and solvent controls were included and gave the expected results. The test substance is concluded to be negative for mutagenicity to bacteria under the conditions of this test.