Amines, C16-18-alkyldimethyl

Genetic toxicity: in vitro

Administrative data

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.

Materials and methods

Type of assay:

in vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

Amines, C16-18-alkyldimethyl

EC Number:

269-915-2

EC Name:

Amines, C16-18-alkyldimethyl

Cas Number:

68390-97-6

Molecular formula:

R-N(Me)2, whereas R= C16-18-alkyl (even numbered, unbranched, saturated)

IUPAC Name:

N,N-dimethyl-C16-18-(even numbered)-alkyl-1-amines

Results and discussion

Test results

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

Any other information on results incl. tables

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

 

Additional results for C12-18 DMA:

Exp.	Preparation interval	Test item concentration in µg/mL	Polyploid cells in %	Cell numbers in % of control	Mitotic indices in % of control	incl.gaps*	Aberrant cells in % excl.gaps*	with exchanges
Exposure period 4 hrs without S9 mix
I	18 hrs	Solvent control^1	2,7	100	100	2,5	2,5	0,5
		Positive control^2	3,1	n.t	100,8	12	10,55	6,5
		2	2,9	56,9	97,5	3,5	3	1
		3,9	4	69,5	93	3,5	2,5	0
		7,8	2,5	62,7	84,4	2,5	2	0
		Exposure period 18 hrs without S9 mix
II	18 hrs	Solvent control^1	2,3	100	100	1,5	1,5	0,5
		Positive control^3	2,8	n.t	100,8	9,5	9,5^5	6,5
		1	3,1	104,4	97,5	1,5	1,5	1
		2	3,1	64,2	93	1,5	1,5	0
		3,9##	3,2	28,3	84,4	2,8	2,5	0
Exposure period 28 hrs without S9 mix
II	28 hrs	Solvent control^1	1,2	100	100	2	2	0
		Positive control^3*	2,8	n.t	67,1	49	49,05	18
		1	3	72,1	101,9	2,5	2,5	0
		2	4,4	37,7	70,6	3	2	0

*: 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 interval	Test item concentration in µg/mL	Polyploid cells in %	Cell numbers in % of control	Mitotic indices in % of control	incl.gaps*	Aberrant cells in % excl.gaps*	with exchanges
Exposure period 4 hrs without S9 mix
I	18 hrs	Solvent control^1	3,5	100	100	1,5	1	0
		Positive control^2	3,1	n.t	59,6	10,5	10,5^5	2
		3,9	2,4	82,4	121,1	1,5	1,5	0,5
		7,8^P	3,4	96,9	137,8	3	2,5	0,5
		15,6^P	3,3	62,1	128,9	6	4,0^5	0,5
Exposure period 28 hrs with S9 mix
II	28 hrs	Solvent control^1	1,7	100	100	2	1,5	0,5
		Positive control^3*	1,6	n.t	101,4	12	11,5 s	3,5
		3,9	2,6	94,7	101,4	3	2,5	0,5
		7,8^P	2,8	124,9	106,1	4,5	4	0,5
		15,6^P	2,2	97,1	96,4	2,5	2	0,5
		31,3^P	3	32,2	83,9	1,5	1	0

*: 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 mix			with S9 mix
	Exp.I	Exp. II		Exp.I	Exp. II
Exposure period	4 hrs	18 hrs	28 hrs	4 hrs	4 hrs
Recovery	14 hrs	-	-	14 hrs	24 hrs
Preparation interval	18 hrs	18 hrs	28 hrs	18 hrs	28 hrs

 

Exp.	Preparation interval	Exposure period	Concentration in µg/mL
				without S9 mix
I	18 hrs	4 hrs		2	3,9	7,8
II	18 hrs	18 hrs		1	2	3,9
II	28 hrs	28 hrs			1	2
				with S9 mix
I	18 hrs	4 hrs		3,9	7,8^P	15,6^P
II	28 hrs	4 hrs	3,9	7,8^P	15,6^P	31,3^P

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.

Applicant's summary and conclusion

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.