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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
publication
Title:
Genotoxicity of Safrole-Related Chemicals in Microbial Test Systems
Author:
Sekizawa J and Shibamoto T
Year:
1982
Bibliographic source:
Mutation Research. 1982; 101: 127-140

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Version / remarks:
(reliability scoring based on 1997 guideline)
Deviations:
no
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: crystalline
Details on test material:
- Name of test material (as cited in study report): Piperonal
- Analytical purity: 100%
- Source of test material: Tokyo Kasei Kogyo Co., Tokyo

Method

Species / strain
Species / strain / cell type:
other: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and Escherichia coli WP2 uvrA
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
polychlorinated biphenyl (PCB) induced S9 from male Sprague-Dawley rats
Test concentrations with justification for top dose:
300, 600, 1200 and 2400 μg/plate in the presence or absence of external metabolic activation.

Vehicle / solvent:
Dimethyl sulfoxide (DMSO)

Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
furylfuramide
Remarks:
without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
benzo(a)pyrene
other: 2-aminoanthracene
Remarks:
with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION:
Without S9: in agar (plate incorporation)
With S9: preincubation

DURATION
- Preincubation period: 20 minutes at 37°C
- Exposure duration: 48 to 72 hours at 37°C

NUMBER OF REPLICATIONS: 3 to 5 plates per test

Source of test system: Dr. Matsushima, Institute of Medical Science, University of Tokyo, Tokyo
Evaluation criteria:
No data.
Statistics:
Not required.

Results and discussion

Test results
Key result
Species / strain:
other: Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and Escherichia coli WP2 uvrA
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Bacterial killing was reported at the highest test article concentration.
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid

Applicant's summary and conclusion

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

Piperonal was not mutagenic under the conditions of the assay.
Executive summary:

No genotoxicity was observed in any bacterial tester strain incubated with piperonal in the presence or absence of external metabolic activation. Cytotoxicity was reported at the highest concentration tested, suggesting that piperonal was evaluated up to its cytotoxic limit. Positive control substances evaluated in the presence and absence of external metabolic activation demonstrated the sensitivity of the assay.