Registration Dossier

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:
1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well conducted and documented study.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
publication
Title:
Salmonella mutagenicity test: V. Results from testing of 311 chemicals
Author:
Zeiger, E., Anderson, B., Haworth, S., Lawlor, T., Mortelmans, K.
Year:
1992
Bibliographic source:
Environ. Molecular Mutagen., 19, Suppl. 21, 2-141

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
not specified
Principles of method if other than guideline:
Method: other: according to Haworth et al. (1983) with minor variations
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
dibutyl ether (purity > 99 %)

Method

Target gene:
not applicable
Species / strain
Species / strain:
other: Salmonella typhimurium, TA97, TA98, TA100 and TA1535
Details on mammalian cell lines (if applicable):
no data
Additional strain characteristics:
not specified
Metabolic activation:
with and without
Metabolic activation system:
S9
Test concentrations with justification for top dose:
3.3-667 µg/plate
Vehicle:
95% ethanol
Controls
Negative controls:
not specified
Solvent controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: sodium azide, 9-aminoacridine, 4-nitro-o-phenylenediamine, 2-aminoanthracene
Details on test system and conditions:
The Ames test was performed as preincubation test in the absence of exogenous metabolic activation and in the presence of liver S-9 fractions of Aroclor 1254-induced male Sprague-Dawley rats and male Syrian hamsters. An initial toxicity assay to determine the appropriate concentration range for the mutagenicity assay was run. Toxic concentrations were defined as those that produced a decrease in the number of the his+ colonies, or a clearing in the density of the background lawn, or both. In the mutagenicity assay 5 concentrations per test variation were tested in triplicate, and repeat experiments were performed at least one weak following the initial trial. Concurrent solvent (95% ethanol) and positive controls were run with each trial. Positive control substances were in the trials without metabolic activation sodium azide for TA1535 and TA100, 9-aminoacridine for TA97, and 4-nitro-o-phenylenediamine for TA98, and in the trials with metabolic activation 2-aminoanthracene for all strains.
Evaluation criteria:
A chemical was designated nonmutagenic only after it had been tested in all strains without activation, and with 10% and 30% rat and hamster S-9. A chemical was judged mutagenic or weakly mutagenic if it produced a reproducible, dose-related response over the solvent control, under a single metabolic activation condition, in replicate trials.

Results and discussion

Test results
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
other: >/= 100 µg/plate
Vehicle controls valid:
yes
Negative controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'. Remarks: Salmonella typhimurium, TA97, TA98, TA100 and TA1535
Additional information on results:
no data

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative

Dibutyl ether did not produce an dose-dependent increase of the number of his+ revertants/plate in the Salmonella typhimurium strains used neither in the absence nor in the presence of a metabolic activation system. Dose selection appears to be in a suitable range, because a bacteriotoxic effect was observed at the highest dose or the two highest doses tested (without metabolic activation 100 and/or 200 µg/plate with all strains; with metabolic activation depending on bacterial strain, kind and amount of liver S-9 fractions 100, 333, 334, 666 and/or 667 µg/plate). In each test well proven positive controls produced mutagenic effects demonstrating the functionally of the test system.
Executive summary:

In this study, Ames test was performed as preincubation test in the absence of exogenous metabolic activation and in the presence of liver S-9 fractions of Aroclor 1254-induced male Sprague-Dawley rats and male Syrian hamsters. An initial toxicity assay to determine the appropriate concentration range for the mutagenicity assay was run. Toxic concentrations were defined as those that produced a decrease in the number of the his+ colonies, or a clearing in the density of the background lawn, or both. In the mutagenicity assay 5 concentrations per test variation were tested in triplicate, and repeat experiments were performed at least one weak following the initial trial. Concurrent solvent (95% ethanol) and positive controls were run with each trial. Positive control substances were in the trials without metabolic activation sodium azide for TA1535 and TA100, 9-aminoacridine for TA97, and 4-nitro-o-phenylenediamine for TA98, and in the trials with metabolic activation 2-aminoanthracene for all strains.

 

Dibutyl ether did not produce an dose-dependent increase of the number of his+ revertants/plate in the Salmonella typhimurium strains used neither in the absence nor in the presence of a metabolic activation system. Dose selection appears to be in a suitable range, because a bacteriotoxic effect was observed at the highest dose or the two highest doses tested (without metabolic activation 100 and/or 200 µg/plate with all strains; with metabolic activation depending on bacterial strain, kind and amount of liver S-9 fractions 100, 333, 334, 666 and/or 667 µg/plate). In each test well proven positive controls produced mutagenic effects demonstrating the functionally of the test system