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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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, published in peer reviewed literature, minor restrictions in design and/or reporting but otherwise adequate for assessment
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Improved method for mutagenicity testing of gaseous compounds by using a gas sampling bag.
Author:
Araki A, Noguchi T, Kato F and Matsushima T
Year:
1994
Bibliographic source:
Mutation Research, Vol 307, pp 335-344

Materials and methods

Test guideline
Qualifier:
no guideline followed
Deviations:
not applicable
Principles of method if other than guideline:
Mutagenicity test on S. Typhimurium TA98, TA100, TA1535 and TA1537 and E. Coli WP2 uvrA using the developed gas exposure method (using a gas sampling bag as an exposure vessel and a preparation vessel of diluted gas).
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
1,3-Butadiene was obtained from Tokyo Kasei Co. Ltd, Tokyo, Japan.

Method

Target gene:
Not applicable
Species / strainopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Additional strain characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 from Phenobarbitol and 5,6-benzoflavone induced rat liver
Species / strain:
E. coli WP2 uvr A
Additional strain characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9 from Phenobarbitol and 5,6-benzoflavone induced rat liver
Test concentrations with justification for top dose:
Toxic concentration levels or about 50% of the maximum exposure concentration.
Vehicle:
- Vehicle(s)/solvent(s):diluted by HEPA-filtered air
Controls
Negative controls:
not specified
Solvent controls:
not specified
True negative controls:
not specified
Positive controls:
not specified
Positive control substance:
not specified
Remarks:
The objective was to develop an improved method for testing gases. Use of standard positive and negative control substances was not stated, but the data presented indicates that that an air control was used.
Details on test system and conditions:
1,3-butadiene was used as a positive control for mutagenicity testing by the gas exposure method using a gas sampling bag with or without metabolic activation. Bacterial plates were made by the agar overlay method with 2mL top agar per plate, 100 µl of S9 per plate, exposure temperature of 37°C, exposure period of 48 h and exposure volume of 500 mL gas per plate. Tests were performed at toxic concentration levels or about 50% levels as the maximum exposure concentration

The above conditions were selected on the basis of the results of a preliminary study with 1,3-butadiene in which the effect of the volume of gas per plate (357, 625, 1250, 2500 or 5000 ml/plate, corresponding to 14, 8, 4, 2 or 1 plates/bag), the amount of S9 (50, 100, 200 or 400 microlitres/plate), the exposure temperature (30 or 37 degrees C), exposure time (2, 4, 14, 24 or 48 hours), the amount of top agar (0, 1, or 2 mL/plate) were examined.
Evaluation criteria:
After incubation, the number of revertant colonies was counted.
Statistics:
None

Results and discussion

Test resultsopen allclose all
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvr A
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity:
no, but tested up to limit concentrations
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity:
no, but tested up to limit concentrations
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Species / strain:
other: S. typhimurium TA 1537, TA 98, TA 100 and E. coli WP2 uvr A
Metabolic activation:
with
Genotoxicity:
negative
Cytotoxicity:
no, but tested up to limit concentrations
Vehicle controls valid:
not specified
Negative controls valid:
not specified
Positive controls valid:
not specified
Remarks on result:
other: strain/cell type:
Remarks:
Migrated from field 'Test system'.
Additional information on results:
1,3-butadiene caused a dose-related marginal increase in revertants in TA 100 in the presence of S9 but this was classified as a negative result.

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative without metabolic activation
positive with metabolic activation

1,3-butadiene was mutagenic in S. typhimurium strain TA1535 in the presence of metabolic activation.
Executive summary:

1,3 -butadiene was tested for mutagenicity, with and without metabolic activation, in S. typhimirium strains: TA 1535, TA 1537, TA 98 and TA 100 andE. Coli WP2 uvr A, using gas sampling bags as both exposure and preparation vessels.

It was not mutagenic to S. typhimurium TA98, TA100, TA1535, TA 1537 and E.coli WP2uvrA without metabolic activiation or to S. typhimurium TA98, TA 1537 and E.coli WP2uvrA with metabolic activation.

1,3 -butadiene was mutagenic to S. typhimurium TA1535 with metabolic activation.

There was a dose-related marginal increase in revertant colonies in S. typhimurium TA100 under the same conditions which was classified as a negative result by the authors of the report.