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

Endpoint summary

Additional information

There are reliable in vitro studies available to assess the potential of the test substance for both gene mutations in bacteria and cytogenicity in mammalian cells.

Gene mutation in bacteria

In a GLP conform study according to OECD guideline 471, the substance MGDN (purity: 97.9 %) was tested for its mutagenic potential based on the ability to induce point mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium TA 1535, TA 100, TA 1537, TA 98 and Escherichia coli WP2 uvrA (BASF 1998). Two independent assays were performed, a standard plate test (SPT) and a preincubation test (PIT), both with a dose range of 20 µg - 5000 µg/plate, and both with and without metabolic activation (Aroclor 1254-induced rat liver S-9 mix).

An increase in the number of his+ or trp+ revertants was not observed in the standard plate test or in the preincubation test either without S-9 mix or after the addition of a metabolizing system. No precipitation of the test substance was found. A slight decrease in the number of revertants was occasionally observed.

According to the results of the present study, the test substance MGDN is not mutagenic in the Salmonella typhimurium/ Escherichia coli reverse mutation assay under the experimental conditions chosen here.

Gene mutation in mammalian cells

no data

Cytogenicity in mammalian cells

In a GLP conform study according to OECD guideline 473, the substance MGDN (purity: 99.9 weight-%) was assessed for its potential to induce structural chromosomal aberrations (clastogenic activity) and/or changes in the number of chromosomes (aneugenic activity) in V79 cells in vitro both in the presence and in the absence of a metabolizing system.

According to an initial range-finding cytotoxicity test for the determination of the experimental doses (the test substance did not exhibit any pronounced toxicity up to the highest recommended doses, i.e. 1 500 μg/mL (ca. 10 mM), the following doses were tested (the test groups in brackets were not evaluated):

- 1st experiment:

4-hour exposure, 18-hour sampling time, without S-9 mix: 0; (187.5) ; 375.0; 750.0; 1500 µg/mL;

4-hour exposure, 18-hour sampling time, with S-9 mix: 0; (187.5) ; 375.0; 750.0; 1500 µg/mL

- 2nd experiment (confirmation of the results of the 1st experiment including continuous exposure and a second sampling time)

18-hour exposure, 18-hour sampling time, without S-9 mix: 0; (187.5) ; 375.0; 750.0; 1500 µg/mL

18-hour exposure, 28-hour sampling time, without S-9 mix: 0; (375.0; 750.0;) 1500 µg/mL

4-hour exposure, 28-hour sampling time, with S-9 mix: 0; (187.5) ; 375.0; 750.0; 1500 µg/mL

About 2- 3 hours prior to harvesting the cells, Colcemid was added to arrest cells at a metaphase-like stage of mitosis (c-metaphases). After preparation of the chromosomes and staining with Giemsa, 100 metaphases for each culture in the case of the test substance, and vehicle controls, or 50 cells for each culture in the case of the concurrent positive controls, were analyzed for chromosomal aberrations.

The negative controls (vehicle controls) gave frequencies of aberrations within the range expected for the V79 cell line. Both of the positive control chemicals, i.e. EMS and cyclophosphamide, led to the expected increase in the number of cells containing structural chromosomal aberrations.

On the basis of the results of the present study, the test substance did not cause any increase in the number of structurally aberrant metaphases incl. and excl. gaps at both sampling times either without S-9 mix and/or after adding a metabolizing system in two experiments performed independently of each other. No increase in the frequency of cells containing numerical aberrations was demonstrated either. Thus, under the experimental conditions of this assay, MGDN is considered not to be a chromosome-damaging (clastogenic) agent under in vitro conditions in V79 cells.

Short description of key information:
in vitro
Gene mutation in bacteria
Ames test, S. typhimurium/ E.coli, with and without metabolic activation: negative (GLP, OECD 471; BASF AG 1998)

Gene mutation in mammalian cells
no data

Cytogenicity in mammalian cells
Chromosome aberration assay, V79 cells, with and without metabolic activation: negative (GLP; OECD 473; BASF AG 2006)

in vivo
no data

Endpoint Conclusion:

Justification for classification or non-classification

Based on the available in vitro studies, there is no indication for a mutagenic potential of the test substance.