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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:
comparable to guideline study with acceptable restrictions
Remarks:
The restrictions were that the number of cells evaluated does not comply with the current guideline. It was conducted in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 473 (In Vitro Mammalian Chromosome Aberration Test)
Deviations:
yes
Remarks:
The number of cells analysed does not comply with the current guideline
GLP compliance:
yes
Type of assay:
in vitro mammalian chromosome aberration test

Test material

Constituent 1
Chemical structure
Reference substance name:
3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate
EC Number:
241-165-0
EC Name:
3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate
Cas Number:
17096-07-0
Molecular formula:
C16H38O5Si4
IUPAC Name:
3-[3,3,3-trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate
Test material form:
other: liquid

Method

Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Details on mammalian cell type (if applicable):
- Type and identity of media: Ham's F12 medium
- Properly maintained: yes
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254 induced S9 mix in rat liver
Test concentrations with justification for top dose:
5000, 2500, 1250, 625, 312.5, 156.3, 78.1, 39.1, 19.5, and 9.8 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: DMSO
- Justification for choice of solvent/vehicle: none given in the study report
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
mitomycin C
Remarks:
without metabolic activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
Remarks:
DMSO
True negative controls:
no
Positive controls:
yes
Positive control substance:
other: Dimethylnitrosamine
Remarks:
with metabolic activation
Details on test system and experimental conditions:
ACTIVATION: 1ml of S9 mix consisted of the following co-factors: S9 0.4 ml, MgCl2 33 µmol, KCL 8 µmol, Glucose-6-phosphate 5 µmol, NADH 4 µmol, NADPH 4 µmol, buffer pH 7.4 100 µmol. The final concentration of S9 was 4%.
METHOD OF APPLICATION: suspensions of test substance in medium

DURATION

- Exposure duration:
without metabolic activation: 12 or 24 hours
with metabolic activation: 3 hours
- Expression time (cells in growth medium):
with metabolic activation: 9 or 21 hours (3-hour treatment)
- Fixation time (start of exposure up to fixation or harvest of cells): 24 hours

SPINDLE INHIBITOR (cytogenetic assays): Colcemid solution (0.1 µh/ml) added 2 hours before the end of the incubation period
STAIN (for cytogenetic assays): 2% solution of Giemsa

NUMBER OF REPLICATIONS: duplicate cultures

NUMBER OF CELLS EVALUATED: 100 cells per culture

DETERMINATION OF CYTOTOXICITY
- Method: mitotic index

OTHER EXAMINATIONS:
- Determination of polyploidy: yes
Evaluation criteria:
The main criterion to designate a positive result is a statistically significant, dose-related increase in the number of structural chromosome aberrations.
Statistics:
t-test

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:
no cytotoxicity
Vehicle controls validity:
valid
Positive controls validity:
valid
Additional information on results:
ADDITIONAL INFORMATION ON CYTOTOXICITY: No test substance induced polyploidy was observed.

Any other information on results incl. tables

Table 1. Results on chromosome aberration test, without and with metabolic activation

Treatment

Treatment time

Treatment concentration µg/ml

Number of cells observed

Excluding gaps

Including gaps

 

Number of cells with aberrations

 

Without metabolic activation

DMSO

12 hours

-

100

4

8

 

100

2

6

 

200

6 (3.0 %)

14 (7.0 %)

 

24 hours

-

100

2

3

 

100

6

7

 

200

8 (4.0 %)

10 (5.0 %)

 

Test substance SK 5001P

12 hours

625.0

100

3

9

 

100

11

15

 

200

14 (7.0 %)

24 (12.0 %)

 

1250.0

100

1

4

 

100

1

3

 

200

2 (1.0 %)

7 (3.5 %)

 

2500.0

100

2

4

 

100

1

4

 

200

3 (1.5 %)

8 (4.0 %)

 

5000.0

100

2

4

 

100

1

4

 

200

3 (1.5 %)

8 (4.0 %)

 

24 hours

625.0

100

0

3

 

100

0

3

 

200

0 (0.0 %)

6 (3.0 %)

 

1250.0

100

3

5

 

100

3

7

 

200

6 (3.0 %)

12 (6.0 %)

 

2500.0

100

1

3

 

100

4

8

 

200

5 (2.5 %)

11 (5.5 %)

 

5000.0

100

3

3

 

100

2

11

 

200

5 (2.5 %)

14 (7.0 %)

 

Positive control

(MMC)

12 hours

0.05

100

40

51

 

100

45

50

 

200

85 (42.5 %)

101 (50.5 %)

 

24 hours

0.05

100

81

86

 

100

86

86

 

200

167 (83.5 %)

172 (86.0 %)

 

With metabolic activation

DMSO

3 hour treatment, 9 hours recovery time

-

100

2

7

 

100

3

7

 

200

5 (2.5 %)

14 (7.0 %)

 

Treatment Substance

SK 5001P

625.0

100

4

8

 

100

3

8

 

200

7 (3.5 %)

16 (8.0 %)

 

1250.0

100

4

9

 

100

0

2

 

200

4 (2.0 %)

11 (5.5 %)

 

2500.0

100

1

5

 

100

5

9

 

200

6 (3.0 %)

14 (7.0 %)

 

5000.0

100

0

6

 

100

4

11

 

200

4 (2.0 %)

17 (8.5 %)

 

Positive control

(DMN)

 

2000.0

100

26

30

 

100

24

28

 

200

50 (25.0 %)

58 (24.0 %)

 

DMSO

3 hours treatment, 21 hours recovery time

-

100

2

4

 

100

6

15

 

200

8 (4.0 %)

19 (9.5 %)

 

Treatment Substance

SK 5001P

625.0

100

2

5

 

100

2

7

 

200

4 (2.0 %)

12 (6.0 %)

 

1250.0

100

2

5

 

100

0

3

 

200

2 (1.0 %)

8 (4.0 %)

 

2500.0

100

0

6

 

100

1

7

 

200

1 (0.5 %)

13 (6.5 %)

 

5000.0

100

2

4

 

100

6

9

 

200

8 (4.0 %)

13 (6.5 %)

 

Positive control

(DMN)

2000.0

100

31

36

 

100

36

39

 

200

67 (33.5 %)

75 (37.5 %)

 

Table 2. Mitotic index in Chinese hamster ovary cells treated with SK 5001P

Treatment

Concentration µg/ ml

 

Mitotic index (%)

12 h

24 h

Without metabolic activation

Control (DMSO)

2.5

2.1

625.0

0.7

2.0

1250.0

0.6

0.9

2500.0

0.6

1.4

5000.0

1.3

1.0

With metabolic activation

Control (DMSO)

13.6

6.2

625.0

11.4

3.3

1250.0

14.2

6.3

2500.0

11.4

4.7

5000.0

13.7

5.4

MMC - mitomycin C

DMN - Dimethylnitrosamine

Applicant's summary and conclusion

Conclusions:
3-[3,3,3-Trimethyl-1,1-bis[(trimethylsilyl)oxy]disiloxanyl]propyl methacrylate has been tested in a valid study according to a protocol similar to OECD 473 and under GLP, up to limit concentrations. No increase in the number of cells with aberrations was observed either with or without metabolic activation in Chinese hamster Ovary cells. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for the induction of chromosome aberrations under the conditions of this study.