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Toxicological information

Genetic toxicity: in vitro

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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:
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

Reference
Name:
Unnamed
Type:
Constituent

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.