Registration Dossier

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

In vitro

Gene mutation properties of dimethylamine were investigated in a bacterial reverse mutation assay (Ames test). This test was performed according to Haworth, S. et al.: Environ. Mutagen. 5, Suppl. 1, 3-142 with Salmonella typhimurium TA1535, TA1537, TA98, TA100, and TA 97. The concentrations of the test substance ranged from 0.000, 33.000, 100.000, 333.000, 1000.000, 3333.000 and 4000.000 or 4500.000 µg/plate using the pre-incubation method in either the presence or absence of 10% rat or hamster liver metabolic activation. The highest in some strains nontoxic dose tested was 1000.000 mg/plate and the test result was negative according to all strains, with and without metabolic activation. (Zeiger et al., 1987).

Hsie et al. reported in 1987 an multiple-endpoint mutagenesis test was performed (Hsie et al., 1987). Chinese Hamster Ovary (CHO) cells were used with and without metabolic activation system. The test concentration of dimethylamine was up to 22 mM. Before performing this experimental study it was known that DMA is a noncarcinogen. It was used as analogue to the cancerogen DMN (dimehylnitrosamine).

Additionally, an in vitro mammalian chromosome aberration test with CHO cells testing among various other chemicals DMA-HCl showed no chromosomal aberrations and no mutations, therefore is stated that DMA is not genotoxic nor cytotoxic in concentrations um to 0.12 mg/mL (Ishidate et al., 1977).

In vivo

In an in Vivo Mammalian Chromosome Aberration Assay (Isakova et al., 1971), Wistar rats were exposed to vapours of DMA by inhalation at concentrations of 0.05 mg/m³ and 1 mg/m³ during 15 and 90 days. The incidence of structural chromosome breakages and aneuploidy, recorded in metaphases of marrow cells, was used as the criterion of a mutagenic effect. The control was provided by the incidence of similar breakages in the marrow of intact rats of the same age and sex, maintained under identical conditions. 50 to 100 metaphases were analyzed for each experimental and control animal.

The incidence of cells with structural chromosome breakages was similar to that in the control preparations (0-2%), and was independent of the duration of poisoning or the concentration of DMA. Analysis of the chromosome count in the same cells revealed that the incidence of aneuploid cells in the experimental animals was somewhat higher than in the controls, for both DMA concentrations and at various times after the beginning of exposure. Statistically significant differences from the controls (p < 0.001) were detected only after 3 month' poisoning, for both DMA concentrations. The incidence of aneuploid cells in the marrow after 90 days poisoning was nearly double that after 15 days poisoning. The significant increase in the incidence of aneuploidy with both DMA concentrations and after different poisoning periods was due to both hypoploid and hyperploid cells.

Since only 50 to 100 metaphases from the bone marrow of each animal were evaluated, the increased aneuploidy and hyperploidy can not be evaluated.

Overall, it can be concluded that DMA is not genotoxic.


Short description of key information:
Zeiger E. et al, 1987, test in Salmonella typhimurium species: no cytotoxicity, no genotoxicity
Hsie et.al., Multiple-endpoint mutagenesis with Chinese Hamster Ovary (CHO) cells: Evaluation with eight carcinogenic and non-carcinogenic compounds, Hemisphere Publishing Corporation) and (Ihidate, and Odashima, 1977) no cytotoxicity, no genotoxicity
Isakova et al., 1971. In vivo Mammalian Chromosome Aberration Assay; no genotoxicity

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

Classification is not warranted according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.