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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, comparable to guideline study; some restrictions in reporting, acceptable for assessment.

Data source

Reference
Reference Type:
other company data
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.77%

Method

Target gene:
his
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
S9 (liver homogenate from rats induced with Aroclor 1254)
Test concentrations with justification for top dose:
0 to 50% (0 to 500,000 ppm)
Vehicle / solvent:
filtered air
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
filtered air
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: chloro-ethylene
Details on test system and experimental conditions:
The cytotoxicity of the test sample in the presence and absence of an activation system, as measured in strain TA 1535, is the basis for selecting concentrations to be used in the mutagenisis experiment.

Exposure was in 9-liter glass chambers. The test gas is mixed with filtered air from a compressed air line and introduced into the chambers through a flow-meter system. The cultures were exposed to gaseous concentrations from 0 to 50% of the test material, for 48 hours at 37 degrees Celsius, both in absence and presence of S9-mix.

The concentrations of the test gas in the chambers are determined (by gas chromatography) at between 2 to 3 hours after the treatment is started and just before the end of the treatment.
Evaluation criteria:
The total revertant colony number at each treatment condition is compared independently with the total revertant colony number for the appropriate negative control. Significance is judged at the 0.01 probability level.
A test sample is classified as mutagenic if both a statistically significant increase in total revertant colony number (p ≤ 0.01) and a dose response (p ≤ 0.05) are observed.
Statistics:
Number of revertants for each dose group: z-test
Dose dependency: Spearman rank test.

Results and discussion

Test resultsopen allclose all
Species / strain:
other: S. typhimurium TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
not specified
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
from 10%
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
In the cytotoxicity experiment the substance was not toxic for strain TA 1535 at concentrations up to 50%.
Strain TA 1535 reverted significantly at concentrations of 10% and above only in presence of the activation system (number of revertant colonies increased maximally 2.6 times those of controls).
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion