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Toxicological information

Genetic toxicity: in vitro

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Administrative data

Endpoint:
in vitro gene mutation study in mammalian cells
Remarks:
Type of genotoxicity: gene mutation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline, with acceptable restrictions. The restrictions were that only 5 concentrations were used and there were no duplicates, although the experiment was repeated.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 476 (In Vitro Mammalian Cell Gene Mutation Test)
Version / remarks:
1984
GLP compliance:
yes
Type of assay:
mammalian cell gene mutation assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent

Method

Target gene:
HPRT
Species / strain
Species / strain / cell type:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Metabolic activation system:
Aroclor induced rat liver S9
Test concentrations with justification for top dose:
1, 10, 50, 75 and 100 µg/ml
Vehicle / solvent:
- Vehicle(s)/solvent(s) used: ethanol
- Justification for choice of solvent/vehicle: none given in report
Controlsopen allclose all
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
ethylmethanesulphonate
Remarks:
300 µg/ml, without activation
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
3-methylcholanthrene
Remarks:
10 µg/ml, with activation
Details on test system and experimental conditions:
METHOD OF APPLICATION: in medium

DURATION
- Preincubation period: none
- Exposure duration: 4 hours
- Expression time (cells in growth medium): none - not clear in report
- Selection time (if incubation with a selection agent): 7 days
- Fixation time (start of exposure up to fixation or harvest of cells):

SELECTION AGENT (mutation assays): selective media

NUMBER OF REPLICATIONS: duplicate cultures

NUMBER OF CELLS EVALUATED:

DETERMINATION OF CYTOTOXICITY
- Method: cloning efficiency;
Evaluation criteria:
Positive if induces statistically significant dose related increase in mutant frequency at dose levels resulting in greater than 50% cell survival, and significantly above the maximum spontaneous mutant frequency.
Statistics:
t-test

Results and discussion

Test results
Species / strain:
Chinese hamster Ovary (CHO)
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Remarks:
100 µg/ml
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.

Any other information on results incl. tables

Table 1 Results of Mammalian mutagenicity with CHO cells Test 1 with and without activation (mean of 5 replicates)

Concentration µg/ml

Activation

Cloning efficiency

Mutant frequency (x10-6)

0

-

71

6+/-3

0 (HO only)

-

72

6+/-3

1

-

73

0+/-0

10

-

76

1+/-3

50

-

71

1+/-3

75

-

76

0+/-0

100

-

95

1+/-2

Positive control

-

68

500+/-92***

0

+

74

3+/-4

0 (HO only)

+

71

7+/-9

1

+

67

1+/-3

10

+

64

0+/-0

50

+

78

0+/-0

75

+

79

0+/-0

100

+

79

4+/-3

Positive control

+

73

271+/-34***

* Solvent control

** Negative control with medium only

*** Statistically significant

Table 2 Results of Mammalian mutagenicity with CHO cells Test 2 with and without activation (mean of 5 replicates)

Concentration µg/ml

Activation

Cloning efficiency

Mutant frequency (x10-6)

0

-

92

0+/-0

0 (HO only)

-

89

6+/-7

1

-

84

11+/-8

10

-

93

0+/-0

50

-

91

0+/-0

75

-

89

2+/-5

100

-

96

0+/-0

Positive control

-

82

384+/-58***

0*

+

74

4+/-4

0**

+

81

15+/-3

1

+

80

0+/-0

10

+

83

0+/-0

50

+

75

1+/-3

75

+

92

13+/-3 ***

100

+

83

0+/-0

Positive control

+

83

382+/-54***

* Solvent control

** Negative control with medium only

*** Statistically significant

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information):
negative with and without metabolic activation

Triethoxy(isobutyl)silane has been tested in a valid study conducted according to OECD 476 and in compliance with GLP. No statistically and biologically significant increase in the mutant frequency was observed in Chinese hamster ovary cells tested with and without metabolic activation. Appropriate solvent and positive controls were included and gave expected results. It is concluded that the test substance is negative for mutagenicity to mammalian cells under the conditions of the test.