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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:
Not stated.
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions
Remarks:
The study was conducted according to an EU test method but full details are not available. It was compliant with GLP. The restrictions were that no units for concentration of the test material was provided and only the positive control with activation was not adequate to test S9 efficacy.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: EEC directive L251, 27, 137 1984
Deviations:
yes
Remarks:
no Units for concentration of the test material was provided and the only positive control with activation was not adequate to test S9 efficacy.
GLP compliance:
yes
Type of assay:
bacterial reverse mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent

Method

Target gene:
his operon for S. typhimurium strains and trp operon for E. coli strains.
Species / strainopen allclose all
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Species / strain / cell type:
E. coli WP2
Metabolic activation:
with and without
Metabolic activation system:
cofactor supplemented post-mitochondrial fraction (S9 mix), prepared from the livers of rats treated with Aroclor 1254.
Test concentrations with justification for top dose:
312.5, 625, 1250, 2500 and 5000 µg/plate - with and without metabolic activation.
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: Ethanol.
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-Anthramine
Remarks:
with metabolic activation: All strains; 10 µg/plate
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
methylmethanesulfonate
Remarks:
without metabolic activation:TA-1537; 50 µg/plate
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: TA-98; 10 µg/plate
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: TA-1537; 50 µg/plate
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: TA-1535, TA-100; 10 µg/plate
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium (plate incorporation)

DURATION
- Expression time (cells in growth medium): 72 hours

NUMBER OF REPLICATIONS: triplicates each in two independent experiments.

DETERMINATION OF CYTOTOXICITY
- Method: Not reported.

METABOLIC ACTIVATION SYSTEM: S-9 mix was prepared in accordance with published procedures (Ames, et al, 1975; Matsushima, et al, 1976), using a 9, 000 x g supernatant prepared from Sprague-Dawley adult male rat liver induced by Aroclor 1254 five days prior to kill.
Evaluation criteria:
Not reported
Statistics:
Not reported

Results and discussion

Test resultsopen allclose all
Species / strain:
E. coli WP2
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
Species / strain:
other: TA 1535, TA 1537, 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:
Not reported

Applicant's summary and conclusion

Conclusions:
Interpretation of results: negative with and without metabolic activation

In a bacterial mutagenicity assay according to EEC directive L251, 27, 137 1984 and to GLP, no mutagenic effect was seen in any of the strains tested. Appropriate solvent and positive controls were included and gave expected results. The test substance is non-mutagenic in test strains used.