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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: Comparable to guideline study with acceptable restrictions: Documentation limited, but individual revertant counts are available.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1986

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Preincubation method with and without metabolic acitvation from rat + hamster (strains: (TA 97), TA98, TA 100, TA 1535, TA 1537), according to Haworth S et al.: Environ. Mutagen. 5, Suppl. 1, 3-142 (1983)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: 82 - 98 % (no explanation for the range)
- Other: from Eastman Chemical Prod.
- impurities: no data

Method

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:
from male Syrian hamster and male SD rat liver, either Arochlor-induced
Test concentrations with justification for top dose:
33 - 10,000 µg/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: water
Controls
Untreated negative controls:
not specified
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
not specified
Positive controls:
yes
Positive control substance:
not specified
Details on test system and experimental conditions:
METHOD OF APPLICATION: preincubation

NUMBER OF REPLICATIONS: 3

Results and discussion

Test resultsopen allclose all
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Remarks:
precipitation at >= 1000 µg/plate
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with
Genotoxicity:
positive
Remarks:
with >= 10 % S9 from hamster liver (negative or only slight positive trend in the presence of S9 from rat liver) [see Report Appendix 2, Table No 17]
Cytotoxicity / choice of top concentrations:
no cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not specified
Positive controls validity:
valid
Remarks on result:
other: strain/cell type: S. typhimurium TA 1535, TA 1537, and TA 98
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
positive with metabolic activation in TA 100 only using S9 mix from hamster liver

The result is considered reliable.
Executive summary:

In a comprehensive screening programme ( National Toxicology Program, NTP) using the preincubation variant with Salmonella TA 98, TA 100, TA 1535, TA 1537 with and without metabolic activation from two liver sources (rat and hamster), weakly mutagenic activity was found in TA100 in the presence of 10 % or higher of hamster-liver S9 mix, while at 4 % no mutagenic activity was observed. The use of S9 mix of rat liver failed to induce mutagenic activity or showed only a slight positive trend.