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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
Study period:
June 2, 1978 - June 22, 1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Test was conducted similar to OECD Test Guideline No. 471, no GLP, but acceptable basic data.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
five classes of Salmonella strains included, and Saccharomyces cerevisae in addition; additional phenotypic characteristics of strains not mentioned; maximum concentration: 10 ul/plate; no replication
Principles of method if other than guideline:
Not relevant
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): S-154 lot QH-30701 BO-78-82
- Physical state: Liquid
- Analytical purity: no data
- Lot/batch No.: QH-30701 BO-78-82
- Stability under test conditions: no data
- Storage condition of test material: no data

Method

Target gene:
His-gene: Amino acid histidine, and Trp-gene: amino acid tryptophan
Species / strainopen allclose all
Species / strain / cell type:
Saccharomyces cerevisiae
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Remarks:
in report
Species / strain / cell type:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, and TA 100
Details on mammalian cell type (if applicable):
Not applicable
Additional strain / cell type characteristics:
not specified
Remarks:
in report
Metabolic activation:
with and without
Metabolic activation system:
Rat liver S9 induced by Aroclor 1254
Test concentrations with justification for top dose:
0.01, 0.1, 1.0, 5.0, and 10 ul/plate
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: no data
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: -S9 mix: S. typhimurium TA1535, TA100 and Saccharomyces cerevisae D4: Ethyl Methane Sulfonate; S. typhimurium TA98 and TA1538: 2-Nitrofluorene; S. typhimurium TA1537: Quinacrine Mustard. +S9 mix: All strains: 2-Anthramine
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Selection time (if incubation with a selection agent): S. typhimurium: 48 hours; Saccharomyces cerevisae D4: 3-5 days

SELECTION AGENT (mutation assays): agar containing Histidine or Tryptophan

NUMBER OF REPLICATIONS: only 1 plate per concentration

NUMBER OF CELLS EVALUATED: 10*8

DETERMINATION OF CYTOTOXICITY
- Method: no data
Evaluation criteria:
Strains TA-1535, TA-1537, and TA-1538: if the solvent control value is within the normal range, a chemical that produces a positive dose response over three concentrations with the lowest increase equal to twice the solvent control value is considered to be mutagenic.
Strains TA-98, TA-100, and D4: if the solvent control value is within the normal range, a chemical that produces a positive dose response over three concentrations with the highest increase equal to twice the solvent control value for TA-100 and 2-3 times the solvent control value for strains TA-98 and D4 is considered to be mutagenic. For these strains the dose-response increase should start at approximately the solvent control value.
Statistics:
No data

Results and discussion

Test resultsopen allclose all
Species / strain:
Saccharomyces cerevisiae
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
other: There is no known positive control compound that works with Saccharomyces cerevisae D4 in the activation plate assays. Without metabolic activation: valid positive controls.
Species / strain:
other: S. typhimurium TA 1535, TA 1537, TA 1538, TA 98, and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
not specified
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Additional information on results:
No data
Remarks on result:
other: strain/cell type: D4
Remarks:
Migrated from field 'Test system'.

Applicant's summary and conclusion

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

The results of the tests conducted on the compound in the absence and in the presence of a metabolic activation system were all negative. The test compound, S-154 Lot QH-30701 B0-78-82, did not demonstrate genetic activity in any of the assays conducted in this evaluation and was considered not mutagenic under these test conditions.
Executive summary:

The test compound was examined for mutagenic activity in a series of in vitro microbial assays employing S. typhimurium TA1535, TA1537, TA1538, TA98 and TA100, and Saccharomyces cerevisiae D4. The test was conducted similar to OECD Guideline 471.The compound was tested directly and in the presence of liver microsomal enzyme preparations from Aroclor-1254-induced rats. The compound was tested over a series of concentrations such that there was either quantitative or qualitative evidence of some chemically-induced physiological effect at the highest dose level. This, however, could not be checked. The low dose in all cases was below a concentration that demonstrated any toxic effect. The concentrations used were 0.01, 0.1, 1.0, 5.0, and 10 ul/plate.

The results of the tests conducted on the compound in the absence and in the presence of a metabolic activation system were all negative. The test compound, S-154 Lot QH-30701 B0-78-82, did not demonstrate genetic activity in any of the assays conducted in this evaluation and was considered not mutagenic under these test conditions.