N-[3-(diethylamino)phenyl]acetamide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro gene mutation study in bacteria

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Data is from publication.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Salmonella mutagenicity tests. II. Results from the testing of 270 chemicals

Author:

Mortelmans, K., Haworth, S., Lawlor, T., Speck, W., Tainer, B., and Zeiger, E.

Year:

1986

Bibliographic source:

Environmental Mutagenesis; Volume 8, Issue Supplement S7, pages 1–55, 1986

Reference 2

Reference Type:

publication

Title:

Study ID: 840758

Author:

NTP

Year:

2012

Bibliographic source:

NTP (National Toxicological Program)by Agency for Toxic Substances and Disease Registry; Division of Toxicology/Toxicology Information Branch, 1600 Clifton Road NE, E-29, Atlanta, Georgia 30333

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: refer below principle

Principles of method if other than guideline:

The Salmonella Ames Test: Preincubation method was performed to determine the mutagenic nature of the test compound N,N-dimethylaniline

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Test material

Test material information

Constituent 1

Reference substance name:

N,N-dimethylaniline

EC Number:

204-493-5

EC Name:

N,N-dimethylaniline

Cas Number:

121-69-7

Molecular formula:

C8H11N

IUPAC Name:

N, N-dimethylaniline

Details on test material:

- Name of test material: N,N-dimethylaniline
- Molecular formula: C8H11N
- Molecular weight: 121.182 g/mol
- Substance type: Organic
- Physical state: liquid

Specific details on test material used for the study:

- Name of test material: N,N-dimethylaniline
- Molecular formula: C8H11N
- Molecular weight: 121.182 g/mol
- Substance type: Organic
- Physical state: liquid

Method

Target gene:

histidine

Species / strain

Species / strain / cell type:

S. typhimurium, other: TA1535, TA1537, TA98, and TA100

Details on mammalian cell type (if applicable):

Not applicable

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

Not specified

Metabolic activation:

with and without

Metabolic activation system:

10% RLI = induced male Sprague Dawley rat liver S9,10% HLI = induced male Syrian hamster liver S9

Test concentrations with justification for top dose:

0, 3, 10, 33, 100, 333, 1000 µg/Plate

Vehicle / solvent:

Dimethyl Sulfoxide

Controls

Controls 1

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Dimethyl Sulfoxide

True negative controls:

not specified

Positive controls:

yes

Remarks:

in the absence of S9 activation

Positive control substance:

2-nitrofluorene

Remarks:

For TA98

Controls 2

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Dimethyl Sulfoxide

True negative controls:

not specified

Positive controls:

yes

Remarks:

in the absence of S9 activation

Positive control substance:

sodium azide

Controls 3

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

Dimethyl Sulfoxide

True negative controls:

not specified

Positive controls:

yes

Remarks:

in the presence of S9 activation by 10% HLI/RLI

Positive control substance:

other: 2-aminoanthracene

Details on test system and experimental conditions:

METHOD OF APPLICATION: preincubation method
DURATION
- Exposure duration: 48 hour

Rationale for test conditions:

Not specified

Evaluation criteria:

An increase in the nuber of revertants/plate was noted.

Statistics:

Yes standard deviation was observed.

Results and discussion

Test results

Species / strain:

S. typhimurium, other: TA1535, TA1537, TA98, and TA100

Metabolic activation:

with and without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

not specified

Vehicle controls validity:

valid

Untreated negative controls validity:

not specified

Positive controls validity:

valid

Additional information on results:

RANGE-FINDING/SCREENING STUDIES: The test chemical was initially tested with strain TA100 in the presence and the absence of the metabolic activation systems, over a wide dose range with an upper limit of 10 mg/plate, or less when solubility problems were encountered.

Any other information on results incl. tables

 Strain: TA100

Dose	No Activation  (Negative)		No Activation  (Negative)		10% HLI  (Negative)		10% HLI  (Negative)		10% RLI  (Negative)		10% RLI  (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	85	2.7	93	3.7	123	10	87	3.1	97	2.2	94	9
3	107	3.2	107	8.5			104	4.7			108	11.7
10	89	5.6	102	8	112	8.7	89	6	110	7.9	108	4.8
33	104	11.3	97	10.3	113	1.8	104	3	110	6.2	101	6.2
100	109	12.5	95	9.9	102	9.3	87	3.3	113	4.5	105	2.6
333	102	3.5	81	3.7	122	12.7	93	2.7	119	11.1	102	8.1
1000					40s	9.3			78s	13.4
Positive Control	382	7.7	345	17.7	1336	56.6	1132	40.3	461	26.6	441	9.1

 

Strain: TA1535

Dose	No Activation  (Negative)		No Activation  (Negative)		10% HLI  (Negative)		10% HLI  (Negative)		10% RLI  (Negative)		10% RLI  (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	23	1.9	28	3.7	9	1.9	6	0.3	8	0.6	10	1.2
3	14	0.9	20	3.8			7	1			9	0.3
10	14	3.2	21	2.2	10	1.2	7	2.8	7	0.7	8	2.2
33	16	1.5	18	1.9	8	0.3	4	1.2	6	0	7	0.7
100	15	0.3	18	2.8	6	0.3	7	0.6	7	0.9	6	1
333	15	2.1	20	2.9	7	1.2	6	1	6	1	5	0.9
1000					2s	1			3s	1.2
Positive Control	519	6.8	324	21.2	438	43	452	9.8	158	11.5	187	9.9

s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

Strain: TA1537

Dose	No Activation  (Negative)		No Activation  (Negative)		10% HLI  (Negative)		10% HLI  (Negative)		10% RLI  (Negative)		10% RLI  (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	7	0.9	7	2.7	8	2.3	6	1.7	6	1.9	3	0.9
3	3	0.3	5	1.8			9	1.8			7	0.6
10	4	1.5	5	0	3	0.9	4	1.2	5	0.7	7	0
33	4	0.3	4	0.9	5	0.6	5	0.7	3	0.6	4	0.9
100	6	2.2	3	0	7	0.3	7	0.9	5	1.2	3	0.7
333	2	1.5	5	1.7	5	0.6	6	2.1	5	0.9	4	0
1000					2s	0.9			7s	1.2
Positive Control	556	5.2	154	23.7	298	10.1	339	18.3	128	3.9	105	6.2

Strain: TA98

Dose	No Activation  (Negative)		No Activation  (Negative)		10% HLI  (Negative)		10% HLI  (Negative)		10% RLI  (Negative)		10% RLI  (Negative)
Protocol	Preincubation		Preincubation		Preincubation		Preincubation		Preincubation		Preincubation
ug/Plate	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM	Mean	± SEM
0	14	0.3	15	1.9	27	1.5	30	1.2	17	1.8	25	3.8
3	18	0.7	15	4.5			27	6.6			25	0.6
10	14	0.7	12	2.2	23	5	29	2.1	19	3.5	24	2.6
33	11	2.7	8	0.3	25	0.9	23	4	22	2.8	22	3.9
100	10	1.5	8	0.9	25	2.4	24	3	22	2	22	2.8
333	9	1.8	12	2.5	26	3.4	22	2.5	22	1.9	20	0.7
1000					4s	0.3			8s	4.6
Positive Control	1034	21.2	354	30.5	1104	32.4	1444	62.5	402	17	404	29.7

s = Slight Toxicity; p = Precipitate; x = Slight Toxicity and Precipitate; T = Toxic; c = Contamination

RLI = induced male Sprague Dawley rat liver S9

HLI = induced male Syrian hamster liver S9

 

Applicant's summary and conclusion

Conclusions:

N,N-dimethylaniline indicated negative result for genetic toxicity in Ames test conducted on to S. typhimurium TA98, TA100,TA37 and TA1535 with and without metabolic activation by 10% HLI/RLI S9 system.

Executive summary:

Gene mutation toxicity study was performed to evaluate the mutagenic nature of the test compound N,N-diethylaniline. Salmonella Ames assay was performed by the preincubation method using the Salmonella typhimurium strains TA98, TA100,TA37 and TA1535 with and without S9 metabolic activation system. The test compound gave negative result for genetic toxicity in Ames test conducted on to S. typhimurium TA98, TA100,TA37 and TA153 with and without metabolic activation by 10% HLI/RLI S9 system. Hence, N,N-diethylaniline (RA CAS no 121 -69 -7) is not likely to classify as gene mutant in vitro.