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:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP status unknown, tested according to standard NTP methodology. Minor restrictions in reporting but otherwise adequate for assessment. Not all OECD required tester strains used , but main ones covered .

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Not all OECD required tester strains used , but main ones covered .
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): n-butane

Method

Target gene:
Histidine gene
Species / strain
Species / strain:
other: Salmonella strains TA1535, TA100, TA97 and TA98;
Metabolic activation:
with and without
Metabolic activation system:
Sprague-Dawley rat or Syrian hamster liver S9
Test concentrations with justification for top dose:
1-10000 ug/plate ug/plate
Vehicle:
No data
Controlsopen allclose all
Solvent controls:
yes
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without S9

Migrated to IUCLID6: TA1535, TA100
Positive control substance:
9-aminoacridine
Remarks:
without S9

Migrated to IUCLID6: TA97
Positive control substance:
2-nitrofluorene
Remarks:
without S9

Migrated to IUCLID6: (or 4-nitro-o-phenylenediamine) TA98
Positive control substance:
other: 2-aminoanthracene (or sterigmatocystin) all strains
Remarks:
with S9
Details on test system and conditions:
METHOD OF APPLICATION: preincubation
The plate tests were conducted within a sealed dessicator (gas chamber) for exposure to gaseous substances.

DURATION
- Preincubation period: 20 minutes at 37º C
- Exposure duration: After 20 minutes, agar is added to the cultures and the contents of the tubes are thoroughly mixed and poured onto the surface of Petri dishes containing standard bacterial culture medium.
- Expression time (cells in growth medium): The number of colonies is usually counted after 2 days.

NUMBER OF REPLICATIONS: at least 2
Evaluation criteria:
A positive response was defined as a reproducible, dose-related increase in histidine-independent (revertant) colonies in any one strain/activation combination. An equivocal response was defined as an increase in revertants that is not dose related, is not reproducible, or is not of sufficient magnitude to support a determination of mutagenicity. A negative response was obtained when no increase in revertant colonies is observed following chemical treatment. There was no minimum percentage or fold increase required for a chemical to be judged positive or weakly positive.

Results and discussion

Test results
Species / strain:
other: Salmonella strains TA1535, TA100, TA97 and TA98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity:
not specified
Vehicle controls valid:
yes
Positive controls valid:
yes
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Additional information on results:
Cytotoxicity was observed (reduced numbers of colonies) at the higher dose levels in some tester strains in both the absence and presence of S9.

Any other information on results incl. tables

Rat liver and hamster liver were both used as sources of metabolic activation. All tests with butane gave negative results.

Applicant's summary and conclusion

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

N-butane was non-mutagenic based on the absence of activity in Salmonella (in the presence and absence of rat or hamster S9).
Executive summary:

Salmonella TA 1535, TA100, TA97, and TA98 were exposed to n-butane at concentrations of 1 -10000 ug/plate with or without Sprague-Dawley rat or Syrian hamster liver S9 activation (10% or 30%) according to the standard NTP protocol. N-butane was non-mutagenic in the presence and absence of rat or hamster S9.