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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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
RTC, Rome, Italy
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): N-Butyl-2,2,6,6-tetramethyl-4-piperidinamine (N-Butyl-TAD)
- Substance type: colourless liquid
- Physical state: liquid

Method

Target gene:
his
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Metabolic activation system:
S9 mix from Phenobarbital (i.p.) and beta-Naphtoflavone (oral) induced rat liver
Test concentrations with justification for top dose:
50, 158, 500, 1580, 5000 µg/plate (pre-test);
313, 625, 1250, 2500, 5000 µg/plate (main test)
Vehicle / solvent:
sterile distilled water
Controls
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
(sterile distilled water and DMSO)
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
2-nitrofluorene
sodium azide
cumene hydroperoxide
other: 2- Aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: 1. experiment: plate incorporation, 2. experiment: preincubation

DURATION:
- Preincubation period: approx. 30 min
- Exposure duration: 72 h

SELECTION AGENT (mutation assays): test item

NUMBER OF REPLICATIONS: 3

DETERMINATION OF CYTOTOXICITY: relative total growth
Evaluation criteria:
- negative control in the laboratory historical range for each tester strain
- positive control chemicals produces responses in all tester strains within laboratory historical range
- Mean plate count should be at least two times the concurrent vehicle control group mean at two consecutive dose levels or at the highest practicable dose-level. Additionally, a dose-response relationship showing increasing numbers of mutant colonies with increasing dose-levels must be evident.
- selected dose range should include a clearly toxic concentration or should exhibit limited solubility as demonstrated by the preliminary toxicity range-finding test or should extend to 5 mg/plate
Statistics:
not applicable

Results and discussion

Test results
Key result
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and TA 102
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Slight signs of toxicity were observed at the highest dose-level in some tester strains.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
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

Under conditions tested, test item is considered to be non-mutagenic in Salmonella typhimurium tester strains with and without metabolic activation.