N-methylformanilide

Genetic toxicity: in vitro

Administrative data

Endpoint:

in vitro cytogenicity / chromosome aberration study in mammalian cells

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data from handbook or collection of data

Data source

Reference

Reference Type:

publication

Title:

In vitro gene toxicity study for test chemical in Chinese hamster ovary cells by in vitro mammalian chromosome aberration test.

Author:

National Toxicology Program

Year:

2018

Bibliographic source:

NTP, Chemical effects in biological system, 2018

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)

Principles of method if other than guideline:

To evaluate the mutagenic potential of test chemical in Chinese hamster ovary cells by in vitro mammalian chromosome aberration test.

GLP compliance:

not specified

Type of assay:

other: In vitro mammalian chromosome aberration test

Test material

Test material information

Constituent 1

Reference substance name:

(2E)-3-phenylprop-2-enal

Cas Number:

14371-10-9

Molecular formula:

C9H8O

IUPAC Name:

(2E)-3-phenylprop-2-enal

Method

Target gene:

Not specified

Species / strain

Species / strain / cell type:

Chinese hamster Ovary (CHO)

Details on mammalian cell type (if applicable):

not specified

Additional strain / cell type characteristics:

not specified

Cytokinesis block (if used):

not specified

Metabolic activation:

with and without

Metabolic activation system:

induced male Sprague Dawley rat liver S9

Test concentrations with justification for top dose:

-S9;0,6.4,12.8 and 18.3 µg/mL (Long duration)
0,6.02,7.96 and 10.21 µg/mL (short duration)
+S9; 0,50.2,174.8and 100.3 µg/mL

Vehicle / solvent:

Vehicle
- Vehicle(s)/solvent(s) used: Dimethyl Sulfoxide
- Justification for choice of solvent/vehicle: The test substance is soluble in DMSO.

Controls

Untreated negative controls:

not specified

Negative solvent / vehicle controls:

yes

Remarks:

DMSO

True negative controls:

not specified

Positive controls:

yes

Positive control substance:

other: -S9 mix; Triethylenemelamine +S9 mix; Cyclophosphamide

Details on test system and experimental conditions:

Details on test system and conditions
METHOD OF APPLICATION: In medium
DURATION
- Fixation time (start of exposure up to fixation or harvest of cells):
-S9; 11 hours (Long duration)
10.5 hours(short duration)
+S9; 10.5 hours

Evaluation criteria:

The mammalian cells were observed for chromosome aberration, Chromosome gaps and breaks.

Statistics:

Yes, SD ± Mean was observed.

Results and discussion

Test results

Key result

Species / strain:

Chinese hamster Ovary (CHO)

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

Remarks on result:

other: Nomutagenic effects were observed

Any other information on results incl. tables

Trial #:1   Activation: No Activation    Date: 10/08/1981    Harvest Time: 11 hour(s)   Trial Call: Negative
		Dose µg/mL	Total Cells Examined	Total Aberrations			Complex Aberrations			Simple Aberrations			Other Abs
				No.of Abs	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs
Vehicle Control:	Negative (Not Specified)	0	100	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0
	Dimethyl Sulfoxide	0	100	3	0.030	1.0	0	0.000	0.0	2	0.020	1.0	1	0.010	1.0
Test Chemical:	trans-Cinnamaldehyde	6.4	100	3	0.030	3.0	2	0.020	2.0	1	0.010	1.0	0	0.000	0.0
		12.8	100	2	0.020	2.0	2	0.020	2.0	0	0.000	0.0	0	0.000	0.0
		18.3	100	3	0.030	3.0	1	0.010	1.0	2	0.020	2.0	0	0.000	0.0
Positive Control:	Triethylenemelamine	0.75	100	31	0.310	23.0	12	0.120	12.0	19	0.190	14.0	0	0.000	0.0
Trend:				0.703			0.674			0.294
Probability:				0.241			0.250			0.384

Trial #:1_S9   Activation: Induced Rat Liver S9    Date: 09/24/1981    Harvest Time: 10.5 hour(s)   Trial Call: Negative
		Dose µg/mL	Total Cells Examined	Total Aberrations			Complex Aberrations			Simple Aberrations			Other Abs
				No.of Abs	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs
Vehicle Control:	Negative (Not Specified)	0	100	3	0.030	3.0	3	0.030	3.0	0	0.000	0.0	0	0.000	0.0
	Dimethyl Sulfoxide	0	100	2	0.020	2.0	1	0.010	1.0	1	0.010	1.0	0	0.000	0.0
Test Chemical:	trans-Cinnamaldehyde	50.2	100	2	0.020	2.0	1	0.010	1.0	1	0.010	1.0	0	0.000	0.0
		74.8	100	2	0.020	2.0	2	0.020	2.0	0	0.000	0.0	0	0.000	0.0
		100.3	32	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0
Positive Control:	Cyclophosphamide	25	100	44	0.440	27.0	12	0.120	11.0	22	0.220	18.0	10	0.100	1.0
Trend:				-0.458			0.174			-1.033
Probability:				0.676			0.431			0.849

Trial #:2   Activation: No Activation    Date: 09/24/1981    Harvest Time: 10.5 hour(s)   Trial Call: Weakly Positive
		Dose µg/mL	Total Cells Examined	Total Aberrations			Complex Aberrations			Simple Aberrations			Other Abs
				No.of Abs	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs	No.of Abs.	Abs Per Cell	% Cells With Abs
Vehicle Control:	Negative (Not Specified)	0	100	3	0.030	3.0	1	0.010	1.0	2	0.020	2.0	0	0.000	0.0
	Dimethyl Sulfoxide	0	100	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0	0	0.000	0.0
Test Chemical:	trans-Cinnamaldehyde	6.02	100	1	0.010	1.0	0	0.000	0.0	1	0.010	1.0	0	0.000	0.0
		7.96	100	4	0.040	4.0	2	0.020	2.0	2	0.020	2.0	0	0.000	0.0
		10.21	18	1	0.056	5.0	1	0.056	5.0	0	0.000	0.0	0	0.000	0.0
Positive Control:	Triethylenemelamine	0.75	100	24	0.240	19.0	11	0.110	11.0	12	0.120	10.0	1	0.010	1.0
Trend:				2.334			2.228			1.067
Probability:				0.010			0.013			0.143

Applicant's summary and conclusion

Conclusions:

Test chemical was evaluated for its mutagenic potential in Chinese hamster ovary cells by in vitro mammalian chromosome aberration test. The test result was considered to be non- mutagenic both in the presence and absence of metabolic activation.

Executive summary:

Genetic toxicity in vitro study was assessed for test chemical. For this purpose in vitro mammalian chromosome aberration test was performed .The test material was exposed toChinese hamster ovary cells inthe presence and absence of metabolic activation S9. The concentration of test material used in the presence and absence of metabolic activation were mention below

 

S9;0,6.4,12.8 and 18.3 µg/mL (Long duration)

      0,6.02,7.96 and 10.21 µg/mL (short duration)

+S9; 0,50.2,174.8and 100.3 µg/mL

No chromosome aberration, Chromosome gaps and breaks were observed in the presence or absence of metabolic activation. Therefore test chemical was considered to be non-mutagenic inChinese hamster ovary cells byin vitro mammalian chromosome aberration test. Hence the substance cannot be classified as non -mutagenic in vitro.