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Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information
- Salmonella typhimurium reverse mutation assay (RA to N,N-Dimethyldecanamide; TA1535,TA1537,TA98,TA100and TA102), OECD 471: non-mutagenic (with and without metabolic activation) (Cognis 1999; Hans-Eric Wollny) - V79-HGPRT (RA to 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 (RA to Mixture of N,N-Dimethyldecanamide and N,N-Dimethyloctanamide; CHO cells), OECD 473: not clastogen (with and without metabolic activation) (Bayer 1995; R. Gahlmann) - 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
Endpoint conclusion:
no adverse effect observed (negative)

Additional information

Additional information from genetic toxicity in vitro:

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

Justification for grouping of substances and read-across

There are no reliable data available for the genetic toxicity of N,N-Dimethyldodecan-amide (CAS 3007-53-2). In order to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006, read-across from structurally related substances was conducted.

In accordance with Article 13 (1) of Regulation (EC) No 1907/2006, "information on intrinsic properties of substances may be generated by means other than tests, provided that the conditions set out in Annex XI are met.” In particular for human toxicity, information shall be generated whenever possible by means other than vertebrate animal tests, which includes the use of information from structurally related substances (grouping or read-across).

Having regard to the general rules for grouping of substances and read-across approach laid down in Annex XI, Item 1.5, of Regulation (EC) No 1907/2006, whereby substances may be predicted as similar provided that their physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity, the substance listed below are selected as reference substances for hazard assessment.

 

 

Target Substance

Source Substance 1

Source Substance 2

Source Substance 3

 

N,N-Dimethyldodecan-amide

N,N-Dimethyldecan-amide

N,N-Dimethyloctanamide

Mixture of N,N-Dimethyloctanamide and N,N-Dimethyldecanamide

CAS

3007-53-2

14433-76-2

1118-92-9

67359-57-3

In vitro gene mutation in bacteria

RA to 14433-76-2

OECD 471, negative (BASF, 1999)

OECD 471, negative (BASF, 2009)

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In vitro gene cytogenicity in mammalian cells

RA to 67359-57-3

RA to 67359-57-3

RA to 67359-57-3

OECD 473, CA, negative (Bayer, 1995)

Mammalian gene mutation

RA to 67359-57-3

RA to 67359-57-3

RA to 67359-57-3

OECD 476, HPRT, negative (Bayer, 1994)

In vivo cytogenicity, (eg micro nucleus test)

According to ITS not necessary

According to ITS not necessary

According to ITS not necessary

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The above mentioned substances are considered to be similar on the basis of structural similarity resulting in similar properties and/or activities. The available endpoint information is used to predict the same endpoints for N,N-Dimethyldodecan-amide (CAS 3007-53-2). A detailed analogue approach justification is provided in the technical dossier (see IUCLID Section 13).

 

N,N-Dimethyloctanamide (CAS 3007-53-2)

Ames (bac. gene mutation):

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.

N,N-dimethyldecanamide (CAS 14433-76-2)

Ames (bac. gene mutation):

The test substance N,N-Dimethyldecanamide was tested in a salmonella typhimurium reverse mutation assay (TA1535,TA1537,TA98,TA100and TA102) according to OECD 471 guideline (Cognis 1999; Hans-Eric Wollny) with and without metabolic activation. The test item was tested at the following concentrations:(TA98,TA100): 3; 10; 33; 100; 333; and 1000 µg/plate and(TA1535,TA1537,TA102): 33; 66; 100; 333; 666; and 1000 µg/plate.Toxic effects, evident as a reduction in the number of revertants, occurred between 333 and 1000µg/plate depending on strain and activation. No substantial increase in revertant colony numbers of any of the five tester strains was observed following treatment with N,N-Dimethyldecan-1 -amide at any dose level, neither in the presence nor absence of metabolic activation (S9 mix).In conclusion the test item did not induce gene mutations by base pair changes or frameshifts in the genome of the strains used.

Mixture of dimethylamides (CAS 67359-57-3)

In vitro mammalian gene mutation:

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.

 

In vitro mammalian cytogenicity:

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

There are various in vitro tests available addressing the in vitro gene mutation in bacteria’s and mammal cells as well as the cytogenicity. None of the test shows positive results. Nevertheless all tests are done with source substances but as source and target substance contains the same structure (reactive) elements and show furthers a trend in irritation and toxicity behaviour, also for mutagenicity a comparable action is expected. Therefore data from the source substance is used to judge about the mutagenicity of the target substance. In summary no mutagenicity is expected for the target substance.

Hence, taking reliability, adequacy and availability into account, the following information on repeated dose toxicity is used for assessment:

- Salmonella typhimurium reverse mutation assay (RA to N,N-Dimethyldecanamide; TA1535,TA1537,TA98,TA100and TA102), OECD 471: non-mutagenic (with and without metabolic activation) (Cognis 1999; Hans-Eric Wollny)

- V79-HGPRT (RA to 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 (RA to Mixture of N,N-Dimethyldecanamide and N,N-Dimethyloctanamide; CHO cells), OECD 473: not clastogen (with and without metabolic activation) (Bayer 1995; R. Gahlmann)

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