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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:
11 January 1982 - 21 January 1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
Deviations:
yes
Remarks:
Very abnormal lawn and pindat colonies observed at the highest test concentration (10000 µg/mL).
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): 4236-45-35, Order J-89
- Substance type: clear colorless liquid
- Physical state: liquid
- Analytical purity: responsibility of the Sponsor
- Lot/batch No.: # J-89
- Other: miscible in distilled water
- Stability: there was no apparent change in the physical state of the test or control articles during the assay.

Method

Target gene:
Histidine gene
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Details on mammalian cell type (if applicable):
not applicable
Additional strain / cell type characteristics:
not applicable
Species / strain / cell type:
S. typhimurium TA 1538
Details on mammalian cell type (if applicable):
not applicable
Additional strain / cell type characteristics:
not applicable
Metabolic activation:
with and without
Metabolic activation system:
Arcolor 1254-treated Sprague Dawley rat S9 liver homogenate
Test concentrations with justification for top dose:
10.000, 3333, 1000, 333 and 100 µg/plate
Vehicle / solvent:
solvent(s) used: distilled water
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
sodium azide
Remarks:
without metabolic activation: 1 µg/plate for strains TA 1535 and TA100
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
without metabolic activation: 150 µg/plate for TA1537
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
2-nitrofluorene
Remarks:
without metabolic activation: 5 µg/plate for strains TA1538 and TA98
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-aminoanthracene: 5 µg/plate for all strains
Remarks:
with metabolic activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48-72h

NUMBER OF REPLICATIONS:
negative and positive controls: in triplicate
compound-treated plates: in duplicate

DETERMINATION OF CYTOTOXICITY
- Method: growth inhibition is tested at following concentration: 33.3, 10, 3.3 and 1 mg/mL with strains TA1538 and TA100 ( in duplicate)

Evaluation criteria:
- positive result is defined as a reproducible, dose-related increase in the number of histidine-independent colonies.
- negative result is defined as the absence of a reproducible increase in the number of histidine-independent colonies
Statistics:
not applicable

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:
cytotoxicity
Remarks:
at 10000 µg/mL
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1538
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
at 10000 µg/mL
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
RANGE-FINDING/SCREENING STUDIES: screening study showed cytotoxicity at 10000 ug/plate: abnormal lawn was observed with sparse growth.

COMPARISON WITH HISTORICAL CONTROL DATA: all solvent and positive controls used in the evaluation of the test article were within the acceptable range of mean historical data.

Remarks on result:
other: all strains/cell types tested

Applicant's summary and conclusion

Conclusions:
Interpretation of results:
negative

The substance showed no mutagenic effects in S. typhimurium tester strains both with and without metabolic activation.