Propanenitrile, 2-[bis(cyanomethyl)amino]-

Genetic toxicity: in vitro

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:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 471 (Bacterial Reverse Mutation Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 472 (Genetic Toxicology: Escherichia coli, Reverse Mutation Assay)

GLP compliance:

yes

Type of assay:

bacterial reverse mutation assay

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Name of test substance: MGDN
Batch No.: Gre 3038/F 535
Date of manufacture: September 9 - 11, 1994
Test substance No.: 96/83
Degree of purity: 97.9%
Appearance of consistency: White powder
Storage: Room temperature

Method

Target gene:

His (Salmonella);
Trp (E. coli)

Species / strain

Species / strain 1

Species / strain / cell type:

S. typhimurium TA 1535, TA 1537, TA 98 and TA 100

Details on mammalian cell type (if applicable):

All strains have a defective excision repair System (uvrB), which prevents the repair of lesions which are induced in the DNA, and this deficiency results in greatly enhanced sensitivity of some mutagens. Furthermore, all strains show a considerably reduced hydrophilic polysaccharide layer (rfa), which leads to an increase in permeability to lipophilic substances.
The strains TA 1535 and TA 100 are derived from histidine-prototrophic Salmonella strains by the substitution mutation his G 46 and are used to detect base pair substitutions. TA 1537 and TA 98 are strains for the detection of frameshift mutagens.

Species / strain 2

Species / strain / cell type:

E. coli WP2 uvr A

Details on mammalian cell type (if applicable):

Escherichia coli WP2 uvrA is a derivative of E. coli WP2 with a deficient excision repair and is used to detect substances which induce base pair
substitutions.

Metabolic activation:

with and without

Metabolic activation system:

S9-mix

Test concentrations with justification for top dose:

Experiment 1: 0; 20; 100; 500; 2500 and 5000 µg/plate.
Experiment 2: 0; 20; 100; 500; 2500 and 5000 µg/plate.

Vehicle / solvent:

- Vehicle(s)/solvent(s) used: [DMSO]
- Justification for choice of solvent/vehicle: The test substance was soluble in DMSO

Controls

Untreated negative controls:

other: sterility control

Negative solvent / vehicle controls:

yes

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: 2-aminoanthracene, N-methyl-N´-nitro-N-nitrosoguanidine, 4-nitro-o-phenylendiamine, 9-aminoacridine, N-ethyl-N'-nitro-N-nitrosoguanidin

Details on test system and experimental conditions:

Positive controls:
with S-9 mix: 2.5 µg 2-aminoanthracene (2-AA) (dissolved in DMSO) for the strains TA 100, TA 98, TA 1537 and TA 1535
60 µg 2-AA (dissolved in DMSO) for the strain E. coli WP2 uvrA
without S-9 mix: 5 µg N-methyl-N`-nitro-N-nitrosoguanidine (MNNG) (dissolved in DMSO) for the strains TA 100 and TA 1535
10 µg 4-nitro-o-phenylendiamine(NOPD, dissolved in DMSO) for the strain TA 98
100 µg 9-aminoacridine (AAC) chloride monohydrate (dissolved in DMSO) for the strain TA 1537
10 µg N-ethyl-N'-nitro-N-nitrosoguanidin (ENNG, dissolved in DMSO) for the strain E. coli WP2 uvrA

Experiment 1: Standard plate test.
Experiment 2: Preincubation test.

Evaluation criteria:

In general, a substance to be characterized as positive in the bacterial tests has to fulfill the following requirements:
- doubling of the spontaneous mutation rate (control)
- dose-response relationship
- reproducibility of the results.

Statistics:

no data

Results and discussion

Test results

Test results 1

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:

other: Occasionally a slight decrease in the number of revertants was observed.

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Test results 2

Species / strain:

E. coli WP2 uvr A

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

other: Occasionally a slight decrease in the number of revertants was observed.

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

No test substance precipitation was found.

Remarks on result:

other: all strains/cell types tested

Remarks:

Migrated from field 'Test system'.