N,N-dimethylbutylamine

Endpoint summary

Additional information

No data were located for N,N-dimethylbutylamine (DMBA). Therefore, cross reading from data on n-Butanol, n-Butylacetate und dimethylamine was made, for RAC justification please refer to section 7.1.

Valid data are available for the potential metabolites butanol (butyl acetate liberates butanol) and dimethylamine for gene mutations in bacterial and mammalian cells (CHO cells), on Sister Chromatid exchange (CHO cells), and Chromosome Aberration ((CHO and CHL cells) in vitro. Most of the studies were performed with and without metabolic activation. All results were negative, i.e. neither of the two supporting chemicals was genotoxic in vitro. Outlines are given below.

n-Butanol

in vitro

Valid experimental data were available to assess the genetic toxicity in vitro

 

Gene mutation in bacteria

Butan-1-ol was tested in the Ames test with and without metabolic activation for its ability to induce mutations in the strains S. typhimurium TA 1535, TA 1537, TA 98 and TA 100 in doses up to 10000 µg/plate following a standardized protocol (NTP 1995). All tested strains were negative with and without metabolic activation.

Jung et al. (1992) performed an Ames test with the S. typhimurium strain TA102, which is reliable to detect crosslinking agents. Butan-1-ol was negative with and without metabolic activation in doses up to 5000 µg/plate.

Additionally, a few othertests were also negative (i.e. McCann et al. 1975).

 

Gene mutation in mammalian cells

In a GLP conform HPRT test according to OECD TG 476, the potential of butan-1 -ol to induce gene mutations in the HPRT locus in V79 cells was studied (BASF SE 2010). After exposure to 4 or 24 hours, Butan-1 -ol did not induce gene mutations either with or without metabolic activation in doses up to 740 mg/mL (= ca. 10 mM, limit dose).

Butan-1 -ol did not induce relevant increases in TK mutations in a reliable mouse lymphoma assay with L5178Y cells with or without metabolic activation in noncytotoxic doses (6.25 and 5.0 µL/mL without and with metabolic activation, respectively; Celanese 1978).

 

Cytogenicity in mammalian cells

Butan-1-ol was evaluated in the in vitro mammalian cell micronucleus test of its potential to induce chromosomal aberrations (Lasne et al. 1984). CHL V79 cells were treated with 50 µL/mL (=ca. 41 mg/mL) without metabolic activation and subsequently 4000 to 7000 cells were scored for micronuclei. Butan-1-ol did not cause an increase in micronuclei.

Obe et al. (1977) tested butan-1-ol for its potential to induce DNA damage/repair in a sister chromatide exchange assay with CHO cells without metabolic activation. In doses up to 1% (v/v), Butan-1-ol did not cause an increase in sister chromatide exchanges.

No increase, above negative control, in DNA repair was seen in the umu test with S. typhimurium TA1 535/pSK1 002, with and without metabolic activation in doses up to 27 µg/mL (Nakamura et al. 1987).

 

Other studies

Aneuploidy induction was observed during early germination of Aspergillus nidulans at concentrations up to 1% (v/v), the highest, cytotoxic concentration tested (Crebelli et al. 1989, Val. 3 adopted from the ECETOC JACC dossier). This effect on funghi is considered as not relevant for humans, since micronucleus tests in vitro (reflecting aneuploidy and clastogenicity) were negative.

 

 

Dimethylamine

Bacterial cells: Salmonella typhimurium TA 100, TA 1535, TA1537, TA 98 were exposed to 0, 33, 100, 333, 1000, 3333, 4000, and 45000 µg/plate using the pre-incubation method in either the presence or absence of 10% rat or hamster liver metabolic activation. The highest non-toxic dose was 1000 mg/plate. The number of revertants was not increased in any of the experiments, i.e. dimethylamine was not mutagenic in bacteria (Zeiger et al., 1987).

Aliphatic amines that were also included in this study were all negative. This includes the following substances: allylamine; n-butylamine; sec-butylamine; tert. butylamine; di-allylamine; 1,3-diamonopropane; di-ethylamine; 1,3-dimethylbutylamine; di-n-propylamine; ethyl-n-butylamine; isopropylamine; tri-allylamine; tri-butylamine; tri-ethylamine; tri-isobutylamine.

Mammalian cells:In a genetic toxicity test battery using CHO cells, DMA did not induce gene mutations (HGPRT locus; DMA concentration up to 20 mM tested); marginal effects on chromosome aberration (small increase of aberrant metaphases in the range 1 to 10 mM DMA) and SCE (small increase in the range 1 to 2.5 mM DMA) were seen. In summary, DMA was not genotoxic to mammalian cells in vitro (Hsie et al., 1987).

Chromosome aberration:DMA was negative; cf. mammalian cells, Hsie et al., 1987.

The studies are considered to be valid and supportive for the assessment of N,N-dimethylbutylamine.

Justification for selection of genetic toxicity endpoint
No genetic toxicity data on N,N-dimethylamine were located. Valid data are available for the potential metabolites butanol (butyl acetate liberates butanol) and dimethylamine for gene mutations in bacterial and mammalian cells (CHO cells), on Sister Chromatid exchange (CHO cells), and Chromosome Aberration ((CHO and CHL cells) in vitro. Most of the studies were performed with and without metabolic activation. All results were negative, i.e. neither of the two supporting chemicals was genotoxic in vitro.
The studies are considered to be valid and supportive for the assessment of the parent compound, N,N-dimethylamine. It is concluded that N,N-dimethylamine lacks a genotoxic potential.

Short description of key information:
N,N-dimethylamine is considered to lack a genotoxic potential because related substances were negative in all studies on mutagenicity in bacterial (mutagenicity) and mammalian (mutagenicity, SCE, Chromosome Aberration) cells. No further study in vivo is needed.

Endpoint Conclusion: No study available

Justification for classification or non-classification

No classification proposed because related substances all gave negative results.