Registration Dossier

Toxicological information

Genetic toxicity: in vitro

Currently viewing:

Administrative data

Endpoint:
in vitro gene mutation study in bacteria
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Study completion date: 18 November, 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: As per the methodology proposed by Ames et al
Deviations:
not specified
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 471 (Bacterial Reverse Mutation Assay)
GLP compliance:
no
Type of assay:
bacterial reverse mutation assay

Test material

Constituent 1
Reference substance name:
Reaction mass of 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-bromo-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium hydroxide
IUPAC Name:
Reaction mass of 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-bromo-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium acetate and 6-chloro-2-[4-[ethyl(2-hydroxyethyl)amino]phenyl]-1-methylbenz[cd]indolium hydroxide
Test material form:
solid
Specific details on test material used for the study:
Name: FAT 31064/E
Purity: >95 %

Method

Target gene:
Histidine requiring genes of Salmonella strains
Species / strain
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
microsomal enzymes from rat liver
Test concentrations with justification for top dose:
0.2, 2, 20, 200 and 2000 µg/petri dish;
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: distilled water
Controlsopen allclose all
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
Remarks:
Without S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: N-methyl-N'-nitrosoguanidine
Remarks:
Without S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: daunomycine
Remarks:
Without S9
Untreated negative controls:
yes
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: 2-anthramine
Remarks:
With S9
Details on test system and experimental conditions:
NUMBER OF REPLICATIONS:
- Number of cultures per concentration: Triplicate
- Number of independent experiments : One

METHODS FOR MEASUREMENT OF CYTOTOXICITY
- Method: Background growth inhibition

METHODS FOR MEASUREMENTS OF GENOTOXICIY : Background growth inhibition
Evaluation criteria:
The criteria of mutagenicity used in this test are a doubling of the spontaneous reversion rate and a dose-effect relationship.

Results and discussion

Test resultsopen allclose all
Key result
Species / strain:
other: Salmonella typhimurium TA 98 and TA 1537
Metabolic activation:
with
Genotoxicity:
positive
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
In the mutagenicity tests without and with metabolic activation, due to toxicity of the test material, a slight decline in the number of revertant colonies was occasionally observed with all strains at the highest concentrations.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Key result
Species / strain:
other: Salmonella typhimurium TA 98 and TA 1537
Metabolic activation:
without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
In the mutagenicity tests without and with metabolic activation, due to toxicity of the test material, a slight decline in the number of revertant colonies was occasionally observed with all strains at the highest concentrations.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
In the mutagenicity tests without and with metabolic activation, due to toxicity of the test material, a slight decline in the number of revertant colonies was occasionally observed with all strains at the highest concentrations.
Vehicle controls validity:
valid
Positive controls validity:
valid

Any other information on results incl. tables

No mutagenic effect was observed with the strains TA 1535 and TA 100.

The evidence for mutagenicity existed only in the presence of a liver microsomal enzyme preparation (S-9 mix) from male rats pretreated with Aroclor 1254 at the concentrations of 20 and 200 µg of product per Petri dish with TA 1537, and at 200 µg with TA 98. For these two strains a toxic effect was noted at the highest concentration of the product with a complete disappearance of the background lawn for TA 1537 and a dispersed lawn of auxotrophic bacteria for TA 98.

A toxic effect was also noted with strain TA 100 in the absence of metabolic activation at 2000 µg of product per Petri dish.

Applicant's summary and conclusion

Conclusions:
FAT 31064/F was found to exert a mutagenic action on strains S. typhimurium TA 98 and TA 1537 only in presence of metabolic activation.
Executive summary:

The mutagenic potential of FAT 31064/E was investigated in a bacterial reverse mutation assay according to procedure prescribed by Ames et al.

The substance FAT 31064/E was tested with the Salmonella typhimurium strains TA 1535, TA 1537, TA 98 and TA 100 at concentrations from 0.2 to 2000 µg (or nl) per petri dish - both in the presence and absence of metabolic activation.

A mutagenic effect was observed with strains TA 1537 and TA 98 only in presence of metabolic activation. No mutagenic effect was observed with strains TA 100 and TA 1535. A toxic effect was noted with strains TA 1537 and TA 100 at the highest tested concentrations.