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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
Study period:
2002
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline Study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

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:
Chloro(chloromethyl)dimethylsilane
EC Number:
217-006-6
EC Name:
Chloro(chloromethyl)dimethylsilane
Cas Number:
1719-57-9
Molecular formula:
C3H8Cl2Si
IUPAC Name:
chloro(chloromethyl)dimethylsilane
Test material form:
other: colourless liquid
Details on test material:
Purity 99.4% (GC)

Method

Target gene:
his D 3052
his G 46
his G 428
his C 3076
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
Post-mitochondrial fraction (59 fraction) from rats treated with Aroclor 1254 was prepared according to MARON and AME5 (1983). 59 was collected from 20 - 30 rats.
Test concentrations with justification for top dose:
100, 316, 1000, 3160 and 5000 ug/plate
3 plates per concentration and experiment
Vehicle / solvent:
ethylene glycol dimethylether
Controls
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
cyclophosphamide
methylmethanesulfonate
other: 2-anthracene amide
Details on test system and experimental conditions:
Ethylene glycol dimethylether served as solvent for the test substance and as negative control in all test strains.
Evaluation criteria:
The statistical evaluation of the results of the AMES test is still under discussion
A test chemical is considered to show a positive response if
the number of revertants is significantly increased (p <= 0.05, U-test according to
MANN and WHITNEY, compared with the solvent control to at
least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of
the solvent control for TA 1535 and TA 1537 in both independent experiments;
in addition, a significant (p <= 0.05) concentration (log value)-related effect
(Spearman's rank correlation coefficient, see reference 3.) is observed;
positive results have to be reproducible and the histidine independence of the
revertants has to be confirmed by streaking random samples on histidine-free
agar plates.
Statistics:
The statistical evaluation of the results of the AMES test is still under discussion
A test chemical is considered to show a positive response if
the number of revertants is significantly increased (p <= 0.05, U-test according to
MANN and WHITNEY, compared with the solvent control to at
least 2-fold of the solvent control for TA 98, TA 100 and TA 102 and 3-fold of
the solvent control for TA 1535 and TA 1537 in both independent experiments;
in addition, a significant (p <= 0.05) concentration (log value)-related effect
(Spearman's rank correlation coefficient, see reference 3.) is observed;
positive results have to be reproducible and the histidine independence of the
revertants has to be confirmed by streaking random samples on histidine-free
agar plates.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Remarks:
No precipitation of the test substance occurred up to the highest investigated dose.
Vehicle controls validity:
valid
Untreated negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Two independent experiments were carried out each without and with metabolic
activation, each experiment consisted of 3 plates/concentration.
The first experiment was carried out by the standard plate incorporation method
whereas the second was carried out by the preincubation method.
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

In conclusion, under the present test conditions Chlormethyl-dimethyl-chlorsilan tested
up to 5000 ug/plate caused no mutagenic effect in the Salmonella typhimurium strains
TA 98, TA 100, TA 102, TA 1535 and TA 1537 neither in the plate incorporation test
nor in the preincubation test each carried out without and with metabolic activation
Executive summary:

Chlormethyl-dimethyl-chlorsilan was examined in the 5 Salmonella typhimurium strains

TA 98, TA 100, TA 102, TA 1535 and TA 1537 in two independent experiments, each

carried out without and with metabolic activation (a microsomal preparation derived

from Aroclor 1254-induced rat liver). The first experiment was carried out as a plate

incorporation test and the second as a preincubation test.

Preliminary test

Chlormethyl-dimethyl-chlorsilan was examined in a preliminary cytotoxicity test without

metabolic activation in test strain TA 100. Ten concentrations of Chlormethyldimethyl-

chlorsilan ranging from 0.316 to 5000 ug/plate were examined in the

preliminary test using strain TA 100. Slight cytotoxicity (scarce background lawn) was

noted at the top concentration of 5000 ug/plate. Hence, 5000 ug/plate was chosen as

the top concentration for the main study.

Main study

Five concentrations ranging from 100 to 5000 ug Chlormethyl-dimethylchlorsilan/

plate were employed in two independent experiments each carried out

without and with metabolic activation.

Cytotoxicity

In the plate incorporation test without and with metabolic activation slight cytotoxicity

(scarce background lawn) was noted at the top concentration of 5000 ug Chlormethyldimethyl-

chlorsilan/plate in all test strains.

In the preincubation test without and with metabolic activation pronounced cytotoxicity

(reduction of the number of revertants by more than 50%) was noted at the top

concentration of 5000 ug Chlormethyl-dimethyl-chlorsilan/plate in all test strains and at

3160 ug/plate in test strain TA 102. Scarce background lawn was observed at the

concentrations of 31 60 and 5000 ug Chlormethyl-dimethyl-chlorsil.anlplate in all test

strains.

Mutagenicity

No mutagenic effect (no increase in revertant colony numbers as compared with control

counts) was observed for Chlormethyl-dimethyl-chlorsilan tested up to a concentration

of 5000 ug/plate in any of the 5 test strains in two independent experiments without

and with metabolic activation (plate incorporation or preincubation test).

In conclusion, under the present test conditions Chlormethyl-dimethyl-chlorsilan tested

up to 5000 ug/plate caused no mutagenic effect in the Salmonella typhimurium strains

TA 98, TA 100, TA 102, TA 1535 and TA 1537 neither in the plate incorporation test

nor in the preincubation test each carried out without and with metabolic activation