N,N-dimethyloctanamide

Endpoint summary

Additional information

Valid in vitro data to assess the genetic toxicity of N,N-Dimethyloctanamide are available.

In vitro tests with pure N,N-Dimethyloctanamide:

A study was performed to investigate the potential of N,N-Dimethyloctanamide to induce gene mutations according to the plate incorporation test (experiment I) and the pre-incubation test (experiment 11) using the Salmonella typhimurium strains TA 1535, TA 1537, TA 98, TA 100 and TA 102 according to OECD 471 (Cognis 2009, A. Sokolowski). The assay was performed in two independent experiments both with and without liver microsomal activation. Each concentration, including the controls , was tested in triplicate. The test item was tested at the following concentrations : 3; 10; 33; 100; 333; 1000; 2500 ; and 5000 µg /plate In both experiments, reduced background growth was observed at higher concentrations with and without S9 mix in all strains used. Toxic effects, evident as a reduction in the number of revertants (below the indication factor of 0.5), were observed at higher concentrations with and without metabolic activation in all strains in both experiments. No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with C-SAT 090040 at any dose level, neither in the presence nor absence of metabolic activation (S 9 mix). There was also no tendency of higher mutation rates with increasing concentrations in the range below the generally acknowledged border of biological relevance. Appropriate reference mutagens were used as positive controls and showed a distinct increase of induced revertant colonies.

 

A mixture of N,N-dimethyldecanamide and N,N-Dimethyloctanamide (with traces of N,N-dimethyl-dodecanamide and N,N-dimethyl-hexanamide) was tested in different in vitro genotoxicity tests (see below). It is concluded that, caused by a high amount of N,N-Dimethyloctanamide in the mixture and the fact that the residual contains homologues with a lower and higher molecular weight (mainly N,N-Dimethyldecanamide) which can be assumed to have an similar toxicological behaviour as the mixture, the mixture has an similar behaviour in the different cell tests like pure N,N-Dimethyloctanamide. Therefore the following study results will be used for assessing the genetoxic behaviour of N,N-Dimethyloctanamide

In vitro tests with mixtures of N,N-Dimethylamides:

A study was accomplished to observe the genotoxic potential of a mixture of N,N-Dimethyldecanamide and N,N-Dimethyloctanamide (with traces of N,N-dimethyldodecanamide and N,N-dimethylhexanamide) (Bayer, 1994, S. Brendler-Schwaab). Therefore the test material was assayed for mutagenic activity at the HGPRT locus in V79 cells from 25 to 250 µg/ml both, with and without metabolic activation according to OECD guideline 476. Under both treatment conditions, cytotoxic effects were induced. The vehicle control mutant frequencies were all in the normal range of background frequencies for the assay. In contrast, the positive controls and DMBA induced a distinct mutagenic effect in mutant frequency, which was significantly increased over the negative controls demonstrating the sensitivity of the test system and the ability to detect known mutagens. Following the test substance was considered to be non mutagenic in the V79-HGPRT Forward Mutation Assay both with and without metabolic activation.

Additional the genotoxic potential of a mixture of N,N-Dimethyldecanamide and N,N-Dimethyloctanamide (with traces of N,N-dimethyldodecanamide and N,N-dimethylhexanamide) was tested in an in vitro mammalian chromosome abberation test according to OECD 473 (Bayer 1995; R. Gahlmann). Therefore Chinese hamster ovary cells were treated with the substance at the concentrations of 10, 40 and 160 µg/ml medium without S9 mix and at the concentrations of 7.2, 36 and 180 µg/ml with S9 mix. The test substance induced cytotoxic effects in cells exposed to the highest doses with and without metabolic activation at the early harvest time of 8 hours after the beginning of the treatment. The mitotic indices were markedly reduced to 66.7 and 43.2 % relative to control cells. With one exception (which was considered as uncritical, see study summary), no statistically significant or biologically relevant increases of numbers of metaphases with aberrations were detected 8, 24 or 30 hours after the beginning of the four hour treatment with the test substance with and without S9 mix. Therefore the mixture of N,N-Dimethyldecanamide and N,N-Dimethyloctanamide was not considered to be clastogenic for mammalian cells with and without metabolic activation

 

Assessment of genetic toxicity

In summary there were no hints for gene mutation or cytogenicity from in vitro genotoxicity test performed with the pure N,N-Dimethyloctanamide or from a mixture of N,N-Dimethyldecanamide and/or N,N-Dimethyloctanamide (with traces of N,N-dimethyldodecanamide and N,N-dimethylhexanamide). As it could be concluded that the mixture has an similar toxicological behaviour in the different cell tests like pure N,N-Dimethyloctanamide the results are used for the assessment of pure N,N-Dimethyloctanamide.

 

Following the mutagenicity testing strategy no in vivo experiment is proposed due to this result.

Key study assignment:

For gene mutation an ames test (Cognis 2009, A. Sokolowski) using pure N,N-Dimethyloctanamide is available. This test is rated as very high in quality and reliability and therefore integrated as key study.

For further cytogenicity and gene mutation end points only one reliability study (per endpoint) with the read across substance is available. Therefore all these studies were integrated as key studies.

Short description of key information:
- Salmonella typhimurium reverse mutation assay (N,N-Dimethyloctanamide; TA1535,TA1537,TA98,TA100and TA102), OECD 471: non-mutagenic (with and without metabolic activation) (Cognis 2009, A. Sokolowski)
- V79-HGPRT (mixture of N,N-Dimethyldecanamide and N,N-Dimethyloctanamide; V79), OECD 476: non mutagenic (with and without metabolic activation) (Bayer 1994, S. Brendler-Schwaab)
- Chromosome abberation test (mixture of N,N-Dimethyldecanamide and N,N-Dimethyloctanamide; CHO cells), OECD 473: not clastogen (with and without metabolic activation) (Bayer 1995; R. Gahlmann)

Endpoint Conclusion: No adverse effect observed (negative)

Justification for classification or non-classification

In vitro genotoxicity test and in vitro mutagenicity test does not reveal a positive result.

Due to criteria of GHS (Regulation (EU) 1272/2008) for germ cell mutagens ("The classification in Category 2 is based on: positive evidence obtained from experiments in mammals and/or in some cases from in vitro experiments, obtained from: somatic cell mutagenicity tests in vivo, in mammals; or other in vivo somatic cell genotoxicity tests which are supported by positive results from in vitro mutagenicity assays....") the substance is not to classify as germ cell mutagen. Also according to EU-criteria DSD (67/548/EEC) the available information does not lead to a classification.

Labelling genotoxicity/mutagenicity:

GHS: no classification

DSD: no classification