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Additional information

The in-vitro genetic toxicity of 2-dimethylamino-2-methylpropan-1-ol (DMAMP) was investigated in a bacterial reverse mutation assay (Ames test) according to OECD 471 (Wagner, 1997). The plate incorporation method was conducted with S. typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvrA at concentrations up to 5000 µg/plate. DMAMP did not induce reversions in any of the S. typhimurium strains or in E. coli WP2 uvrA with or without metabolic activation. No cytotoxic effects were observed and all positive controls were valid.

In a study according to OECD 473, the potential of DMAMP to induce chromosomal aberrations was tested in cultured rat (Crl:CD(SD)) lymphocytes (Schisler, 2012). The lymphocytes were exposed to DMAMP at concentrations up to 1172 µg/mL with and without metabolic activation. No increase in chromosomal aberrations was observed in the experiments with short-term treatment (4 h) in the presence or absence of metabolic activation.The mitotic indices of the treated cultures with S9 mix ranged from 77.3 to 95.7% and without S9 mix from 90.2 to 100.6% as compared to the solvent control.Because of the negative results of the short-term treatment, an additional testing without metabolic activation was performed with continuous treatment (24 h). After continuous treatment, DMAMP did also not induce chromosomal aberrations in cultured rat lymphocytes.The mitotic indices ranged from 78.4 to 109.8% relating to the solvent control.

DMAMP was also tested for its potential to cause gene mutations in an in-vitro mammalian cell mutation assay according to OECD 476 (Indrani, 2012). Chinese hamster ovary (CHO-K1) cells were treated with DMAMP at concentrations of up to 1172 µg/mL for 4 h both with and without metabolic activation. After an expression time of 9 days in growth medium, cells were incubated for 10 days with 6 -thioguanine as selection agent for forward mutation at the HPRT locus. Both with and without metabolic activation, no increases in mutant frequency were observed in the initial and in the confirmatory gene mutation assay. There was no evidence of excessive cytotoxicity (i.e., < 10 % relative cloning efficiency) at any of the tested concentrations either in the presence or absence of metabolic activation in any of the experiments performed.

DMAMP showed no evidence of a clastogenic and mutagenic potential with and without metabolic activation in in-vitro test systems.

Justification for selection of genetic toxicity endpoint

There are three GLP guideline studies (all of them Klimisch score 1) available on genetic toxicity in-vitro: Ames test, in-vitro mammalian chromosome aberration test and in-vitro mammalian cell gene mutation test

In order to meet the standard information requirements according to Annex VII-IX, section 8.4 of Regulation (EC) 1907/2006, the studies are required.

Short description of key information:

In-vitro:

Gene mutation (bacterial reverse mutation assay / Ames test): S. typhimurium TA 1535, TA 1537, TA 98, TA 100 and E. coli WP2 uvrA: negative with and without metabolic activation (according to OECD 471)

Chromosome aberration (in-vitro mammalian chromosome aberration test): negative with cultured rat lymphocytes with and without metabolic activation (according to OECD 473).

Gene mutation (in-vitro mammalian cell gene mutation test): negative with Chinese hamster ovary (CHO-K1) cells with and without metabolic activation (according to OECD 476).

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

The available data on genetic toxicity of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.