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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Reliable data from several guideline studies on in-vitro gene-mutation in bacterial cells are available for C10-DMA, C12-DMA, C12-14-DMA, C14-DMA, C16-DMA, C12-18 DMA and C18-DMA. Four reliable in-vitro cytogenetic studies in mammalian cells are available for C10-DMA, C16-DMA, C12-18 DMA and for C18-DMA. In addition, six in-vitro gene mutation studies in mammalian cells are available for the substances C10-DMA, C12-14-DMA, C16-DMA, C12-18 DMA and C18-DMA (all studies are reliable). Further one reliable in vivo cytogenetic study according to OECD TG 474 is available for C12-14-DMA. All studies demonstrate a lack of genotoxic activity of DMAs. Therefore, no classification according to Regulation (EC) No. 1272/2008 is warranted.

Link to relevant study records

Referenceopen allclose all

Endpoint:
in vitro cytogenicity / chromosome aberration study in mammalian cells
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint-specific justification, please see read-across justification document (category approach) in the linked category of dimethylalkylamines.
Type of assay:
in vitro mammalian chromosome aberration test
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Exp I: at concentrations of 15.6 and 31.3 µg/mL, Exp II: at all concentrations
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Results presented above were obtained with the source substance C12-18 DMA.


 


Additional results for C12-18 DMA:





















































































































































































Exp.Preparation intervalTest item concentration in µg/mLPolyploid cells in %Cell numbers in % of controlMitotic indices in % of controlincl.gaps*Aberrant cells in % excl.gaps*with exchanges
Exposure period 4 hrs without S9 mix
I18 hrsSolvent control12,71001002,52,50,5
  Positive control23,1n.t100,81210,556,5
  22,956,997,53,531
  3,9469,5933,52,50
  7,82,562,784,42,520
  Exposure period 18 hrs without S9 mix
II18 hrsSolvent control12,31001001,51,50,5
  Positive control32,8n.t100,89,59,556,5
  13,1104,497,51,51,51
  23,164,2931,51,50
  3,9##3,228,384,42,82,50
Exposure period 28 hrs without S9 mix
II28 hrsSolvent control11,2100100220
  Positive control3*2,8n.t67,14949,0518
  1372,1101,92,52,50
  24,437,770,6320

*: Inclusive cells carrying exchanges


#: Evaluation of 50 metaphase plates per culture


##: Evaluation of 200 metaphase plates per culture


n.t: Not tested


P: Precipitation occurred


S: Aberration frequency statistically significant higher than corrresponding control values


1: Ethanol 0.5%(v/v)


2: EMS 900.0 µg/ml


3: EMS 500.0 µg/mL


 















































































































































Exp.Preparation intervalTest item concentration in µg/mLPolyploid cells in %Cell numbers in % of controlMitotic indices in % of controlincl.gaps*Aberrant cells in % excl.gaps*with exchanges
Exposure period 4 hrs without S9 mix
I18 hrsSolvent control13,51001001,510
  Positive control23,1n.t59,610,510,55 2
  3,92,482,4121,11,51,50,5
  7,8P3,496,9137,832,50,5
  15,6P3,362,1128,964,05 0,5
Exposure period 28 hrs with S9 mix
II28 hrsSolvent control11,710010021,50,5
  Positive control3*1,6n.t101,41211,5 s3,5
  3,92,694,7101,432,50,5
  7,8P2,8124,9106,14,540,5
  15,6P2,297,196,42,520,5
  31,3P332,283,91,510

*: Inclusive cells carrying exchanges


n.t: not tested


P: Precipitation occurred


S: Aberration frequency statistically significant higuer than corrresponding control values


1: Ethanol 0.5 % (v/v)


2: CPA 1.4 µg/mL


3: CPA 2.0 µg/mL


 









































 without S9 mixwith S9 mix
 Exp.IExp. IIExp.IExp. II
Exposure period4 hrs18 hrs28 hrs4 hrs4 hrs
Recovery14 hrs--14 hrs24 hrs
Preparation interval18 hrs18 hrs28 hrs18 hrs28 hrs

 






































































Exp.Preparation intervalExposure periodConcentration in µg/mL
    without S9 mix
I18 hrs4 hrs 23,97,8
II18 hrs18 hrs 123,9
II28 hrs28 hrs  12
    with S9 mix
I18 hrs4 hrs 3,97,8P15,6P
II28 hrs4 hrs3,97,8P15,6P31,3P

P: precipitation occurrred


 


In the absence of S9 mix, 4 hrs exposure resulted in the cell number reduction to 62.7% of control at 7.8 µg/mL. Evaluation of cytogenetic damage at the next higher concentration of 15.6µg/mL was not possible due to the observed high cytotoxicity, the cell number reduction being 3.9% of control. In the experiments with treatment periods of 18 and 28 hrs, evaluation of cytogenetic damage was performed up to the concentrations inducing a cell number reduction to 28.3 and 37.7% of control, respectively.


In the first experiment, in the presence of S9 mix, after 4 hrs exposure with 15.6µg/mL at the 18 hrs preparation interval resulted in a cell number reduction to 62.1% of control. Evaluation of cytogenetic damage at the next higher concentration of 31.3µg/mL was not possible due to the observed high cytotoxicity, the cell number reduction being 3.5% of damage was performed up to the concentration inducing cell number reduction to 32.2 of control.

Executive summary:

The study used as source investigated the in vitro gene cytogenicity of C12-18 DMA. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in the linked category of dimethylalkylamines.

Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint-specific justification, please see read-across justification document (category approach) in the linked category of dimethylalkylamines.
Type of assay:
bacterial reverse mutation assay
Key result
Species / strain:
E. coli WP2 uvr A pKM 101
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
experiment I and II
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1537
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
experiment I and II
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 1535
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
experiment I and II
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
experiment I and II
Vehicle controls validity:
valid
Positive controls validity:
valid
Key result
Species / strain:
S. typhimurium TA 98
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
experiment I and II
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Results presented above were obtained with the source substance C12-18-DMA.
Executive summary:

The study used as source investigated the in vitro gene mutation potential of C12-18-DMA in bacteria. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in the linked category of dimethylalkylamines.

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint-specific justification, please see read-across justification document (category approach) in the linked category of dimethylalkylamines.
Type of assay:
mammalian cell gene mutation assay
Species / strain:
Chinese hamster lung fibroblasts (V79)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Exp I: >= 6 µg/mL without and at 32.0 µg/mL with metabolic activation, Exp II: at 6.ß µg/mL
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Results presented above were obtained with the source substance C12-18 DMA.


 


Additional results for C12-18 DMA:






















































































































































































































































































































































































































































































   relativerelativemutant relativerelativemutant 
 conc.S9cloningcloningcoloniesinductioncloningcloningcolonies/induction
 per mLmixefficiency 1efficiency I10 6 cellsfactorefficiency Iefficiency II106cellsfactor
   %%  %%  
Column12345678910
Experiment I / 4 h treatment Culture Iculture II
Solvent control with ethanol -10010015,9 10010014,4 
Positivw control with EMS -10010010,1110010024,51
Test item150-79,171,4162,910,288,1107,8118,68,2
Test item0,5-97culture was not continued #99,8culture was not continued #
Test item1-107,7culture was not continued # culture was not continued #
Test item2-102,793,911,81,291104,28,50,3
Test item4-32,859,17,80,885,4105,610,50,4
Test item6-18,388,911,51,143,9102,83,10,1
Test item8-14,283,16,40,67,497,719,70,8
Test item12-12,985,610,514,390,13,90,2
Test item16-0culture was not continued ##  0culture was not continued ##
           
Neg.control +1001008,5 1001004,2 
Solv.control with ethanol +87,81001311001002,61
Pos. Control with DMBA2+26,258,91058,912543,145,51217,6289,2
Test item2+9097,25,60,488,589,38,33,2
Test item4+89,89312,71101,487,15,92,2
Test item8+77,5938,10,697,992,25,12
Test item16+82,794,510,20,865,164,38,23,1
Test item32+11,399,210,60,812,18115,86
Test item48+0culture was not continued##  0culture was not continued##  
Experiment II / 24 h treatment culture Iculture II
Negative control -1001006,2 1001005,2 
Solv. Control with ethanol -10010010,411001005,71
Pos.control with EMS75-8090198,331,888,197,1152,629,9
Test item0,5-77,496,89,10,994,197,66,81,2
Test item1-81,5107,37,70,797,177,24,90,9
Test item2-68,9112,64,20,495,986,45,61
Test item4-49,791,53,90,482,375,96,61,2
Test item6-4785,30,5063,314,82,6
Test item8-culture was not continued##culture was not continued##
Test item12-culture was not continued##culture was not continued##
Test item16-culture was not continued##culture was not continued##
Executive summary:

The study used as source investigated the in vitro gene mutation potential of C12-18 DMA in mammalian cells. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in the linked category of dimethylalkylamines.

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint-specific justification, please see read-across justification document (category approach) in the linked category of dimethylalkylamines.
Type of assay:
mammalian cell gene mutation assay
Species / strain:
mouse lymphoma L5178Y cells
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
Exp I: at conc. >= 8.0 µg/mL (without metabolic activation) and 16 µg/mL (with metabolic act.) Exp II: >= 4 µg/ml (without metabolic act.) and >=16 µg/mL with metabolic activation.
Vehicle controls validity:
valid
Untreated negative controls validity:
not examined
Positive controls validity:
valid

Results presented above were obtained with the source substance C12-18 DMA.


 


Additional results for C12-18 DMA:


 


 




















































































































































































































































































































































































































































































































































































   relativerelativemutant relativerelativemutant 
 conc.S9cloningtotalcoloniesinductioncloningtotalcolonies/induction
 µg/mLmixefficiency 1growth106cellsfactorefficiencygrowth106cellsfactor
Column12345678910
Experiment I / 4 h treatment Culture Iculture II
Neg. Control with medium -100100112 10010097 
Pos. Control with MMS19,5-10010012611001001291
Test item0,5-67,8323683,34125,84113,2
Test item1-871301541,2115,499,81311
Test item2-100114,9840,7109,977,9980,8
Test item4-90,3117,6650,5106,473,81190,9
   90,387,3130137,2541150,9
Test item8-1970,61641,31058,71661,3
Test item16-1,7culture was not continued#1,1culture was not continued#
           
Neg.contr.with medium +100100116 10010098 
Solv.control with ethanol +1001001001100100791
Pos. Control with CPA4,5+35,327,3 3,334,527,3  
Test item0,5+116,9culture was not continued ##78,7culture was not continued ##
Test item1+131,687,5204210063,61702,1
Test item2+98,483,71811,89357,81572
Test item4+82,999,41241,275,170,41081,4
Test item8+73,873,41661,771,7581481,9
Test item16+64,940,21521,548,645,61441,8
Experiment II / 24 h treatment-culture Iculture II
Neg.contr.with medium -100100162 10010081 
Solv.control with ethanol -1001009511001001091
Pos.control with MMs13-16,810,7485330,910,87559,4
Test item0,5-8278,11001,110089,51181,1
Test item1-134,178,91261,377,972,11441,3
Test item2-84,469,21561,679,457,71931,8
Test item4-43,524,12212,359,923,82712,5
Test item8-(5,9)(1,7)(129)(1,4)(8,2)(2,9)(191)(1,8)
Test item16-0culture was not continued #1,6culture was not continued #
Test item24-0culture was not continued #0culture was not continued #
Test item32-0culture was not continued #0culture was not continued #
Experiment II / 4 h treatment culture Iculture II
Neg.contr.with medium +100100152 100100  
Solv.control with ethanol +100100891100100  
Pos. Control with CPA4,5+13,916,15273,511,214,4  
Test item2+83,365,71281,482,7155,8  
Test item4+68,688,71271,490,5149,4  
Test item8+105,670,91181,371,3126  
Test item16+42,238,21021,133,568,1  
Test item24+(5,1)(1,1)(1047)(11,7)5,941  
Test item32 1,2culture was not continued #0,2culture was not continued #
Experiment IIA / 24 h treatment culture Iculture II

Neg.contr.with medium   - 100 100 57 1 100 100 83   Solv.control with ethanol   - 100 100 36   100 100 53 1 Pos. Control with MMS 13 - 26,6 20,7 338 6 7,6 15,4 343 4,2 Test item 13 - 53,3 26,6 87 1,5 50,2 44,8 60 1,1 Test item 2 - 43,1 21,8 90 1,6 48,8 44,8 46 0,9 Test item 4 - 25,6 11,3 109 1,9 30,1 37,2 82 1,5 Test item 6 - 21,2 5 63 1,1 20,7 12,6 88 1,7 Test item 8 - (6,3) (1,4) (32) (0,6) (9,9) (3,3) (81) (1,5)

Executive summary:

The study used as source investigated the in vitro gene mutation potential of C12-18 DMA in mammalian cells. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in the linked category of dimethylalkylamines.

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

Genetic toxicity in vivo

Link to relevant study records
Reference
Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
For details on endpoint-specific justification, please see read-across justification document (category approach) in the linked category of dimethylalkylamines.
Type of assay:
micronucleus assay
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Remarks:
in the highest dose group: motor activity decreased, diarrhea, palpebral fissure narrow, movements uncoordinated, stupor, tonic convulsion, and prone position
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid

Results presented above were obtained with the source substance C12-14 DMA.

Executive summary:

The study used as source investigated in vivo cytogenicity of C12-14 DMA. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in the linked category of dimethylalkylamines.

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

Additional information

Eleven reliable in-vitro gene-mutation studies (reliability 1 or 2) in bacteria are available for C10-DMA, C12-DMA, C12-14-DMA, C14-DMA, C16-DMA, C12-18 DMA and C18-DMA. All studies were performed according to the OECD TG 471. The results of these studies are comparable, demonstrating no mutagenic potential of DMAs.


Four in-vitro cytogenetic studies in mammalian cells are available for C10-DMA, C16-DMA, C12-18 DMA and for C18 -DMA. In addition, six in-vitro gene mutation studies in mammalian cells are available for the substances C10-DMA, C12-14-DMA, C16-DMA, C12-18 DMA and C18-DMA. All of these studies were performed according to OECD Guideline 473 or 476 respectively and merit Klimisch rating of 1. No mutagenic/no clastogenic potential was found. Based on the results obtained is not expected that the chain length variation influences the genotoxicity of DMAs.


Further one reliable (reliability 1) in vivo cytogenetic study according to OECD TG 474 is available for C12-14-DMA, demonstrating lack of genotoxic activity of DMAs in vivo as well.


All in all, data on genotoxicity are consistent. In vitro as well as in vivo data showed no genotoxic potential for the members of this category.


No classification according to Regulation (EC) No. 1272/2008 is warranted to members of DMAs and no further testing is needed.

Justification for classification or non-classification

In a reliable set of bacterial mutation assays, gene mutation studies in mammalian cells, and in vitro cytogenicity tests and one in vivo mutagenicity test, the DMAs of this category did not exert mutagenic or clastogenic activity.


Based on the available data no classification for mutagenicity according to Regulation (EC) No. 1272/2008 is necessary.