Propanamide, 3-amino-2,2-dimethyl-

Endpoint summary

Additional information

In vitro

In a first test, the substance 3-amino-2,2-dimethyl-propanamide was tested according to OECD guideline 471 and under GLP (key study, BASF AG, 2005) for its mutagenic potential based on the ability to induce gene mutations in selected loci of several bacterial strains, i.e. Salmonella typhimurium and Escherichia coli, in a reverse mutation assay. The following strains were used: TA98, TA100, TA1535, TA1537 and E. coli WP2 uvrA at dose ranges of 20 to 5000 µg/plate in the standard plate test (SPT) and preincubation test (PIT) both with and without metabolic activation (Aroclor-induced rat liver S-9 mix). No precipitation of the substance was observed. No bacteriotoxic effect was observed. 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 metabolising system. According to the results of this study, the test substance 3-amino-2,2-dimethyl-propanamide is not mutagenic in the Salmonella typhimurium/ Escherichia coli reverse mutation assay under the experimental conditions chosen.

In a second Ames test, the test substance 3-amino-2,2-dimethyl-propanamide was assayed for the mutagenicity by the Bacterial Reverse Mutation Test from the Research Institute for Organic Syntheses (RIOS, 2004) by order of Novartis Pharma AG. The test was performed according to EU method B.13/14 Mutagenicity, which is analogous to the OECD guideline 471. Four indicator Salmonella typhimurium strains, TA 98, TA 100, TA 1535 and TA 1537 and one indicator Escherichia coli strain, WP2 uvrA, were used. The test substance was dissolved in demineralised water and assayed at doses of 50 - 5000 μg which were applied to plates in amount of 0.1 ml. The experiments were performed without metabolic activation and with supernatant of rat liver and mixture of cofactors. In the arrangement given above the test substance 3-amino-2,2-dimethyl-propanamide was non mutagenic for all bacterial strains used with as well as without metabolic activation.

The key study done by ARC and by order of Novartis Pharma AG (2005) was performed to determine possible mutagenic properties of 3 -amino-2,2 -dimethyl-propanamide by means of an in vitro mammalian chromosome aberration test in human lymphocytes, according to the directive 2000/32/EC, B.10 and to the OECD guideline 473. Four experiments were performed: two of them without and two with the use of a metabolic activation system. Primary lymphocyte cultures were established from whole blood freshly obtained from one male donor (two experiments) and from one female donor (two experiments). After 48 hours of incubation, 3-amino-2,2 -dimethyl-propanamide was added. In both experiments with the use of a metabolic activation system and in one experiment without addition of a metabolic activation system the test substance was washed out three hours later and the cultures were cultivated for another 17 hours. In one experiment without a metabolic activation system the cultures were treated with the test substance for 20 hours. In all experiments colcemid was added two hours before the end of the cultivation period, and then cells were fixed and slides prepared. Neither in the experiments without nor in those with a metabolic activation system the mitotic indices were in the test substance treated cultures markedly reduced compared to the corresponding negative controls. They ranged between 79.9% and 113.8% of those of the corresponding negative controls. No statistically significant differences in the number of metaphases with numerical aberrations were noted in any experiment performed at any concentration analysed compared to the concurrent negative controls, regardless whether a metabolic activation system was used or not. No statistically significant increases in the number of metaphases with structural aberrations or with gaps were noted in any experiment performed at any concentration analysed compared to the concurrent negative controls, regardless whether a metabolic activation system was used or not. All figures were within the range of historical negative controls.

In vivo

There are no data available concerning genetic toxicity in vivo.

Short description of key information:
in vitro:
Ames test: negative (OECD guideline 471)
Ames test: negative (EU Method B.13/14)
Chromosome aberration test: negative (EU Method B.10)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Based on the results of the available in vitro genetic toxicity studies, 3-amino-2,2-dimethyl-propanamide does not have to be classified according to Directive 67/548/EEC and according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.