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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report date:
1998

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane
EC Number:
240-212-2
EC Name:
4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane
Cas Number:
16068-37-4
Molecular formula:
C14H34O6Si2
IUPAC Name:
4,4,7,7-tetraethoxy-3,8-dioxa-4,7-disiladecane
Test material form:
other: liquid

Test animals

Species:
mouse
Strain:
ICR
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 6-8 weeks
- Weight at study initiation: males 25.3-33.0 g, females 21.6-28.8 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Fasting period before study:
- Housing: mice of the same sex were house 1 per cage in polycarbonate solid bottom cages which were maintained on stainless steel racks equipped with automatic watering manifolds and were covered with filter material. Heat-treated hardwood chips were used for bedding
- Diet (e.g. ad libitum): ad libitum - certified laboratory rodent chow (certified Rodent 7012C)
- Water (e.g. ad libitum): ad libitum - tap water
- Acclimation period: no less than 7 days after receipt

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72±3
- Humidity (%): 50±20
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
sesame oil
Details on exposure:
Male and female mice were dose by a single oral gavage of 75, 150 or 300 mg/kg bw which was administered in a total volume of 10 ml test article-vehicle mixture/kg bw.
Duration of treatment / exposure:
24 or 48 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
75, 150, 300 mg/kg bw
Basis:

No. of animals per sex per dose:
10 - vehicle control, low test dose (75 mg/kg), mid test dose (150 mg/kg)
15 - high test dose (300 mg/kg)
5 - CP (60 mg/kg), MMC (2 mg/kg)
Control animals:
no
Positive control(s):
cyclophosphamide
- Justification for choice of positive control(s): none given
- Route of administration: oral (gavage)
- Doses / concentrations: 10 ml/kg bw

mitomycin
- Justification for choice of positive control(s): none given
- Route of administration: intraperitoneal injection
- Doses / concentrations: 10 ml/kg

Examinations

Tissues and cell types examined:
At 24 and 48 hours post-exposure, bone marrow was collected from the femur of 5 animals in all groups for micronucleus assay.
Details of tissue and slide preparation:
The bone marrow cells were pelleted by centrifugation at approximately 100 x g for 5 minutes and the supernatant was drawn off.
The cells were resuspended by aspiration with a capillary pipette and a small drop of bone marrow suspension was spread onto a clean glass slide.
2-4 slides were prepared from each mouse. The slides were fixed in methanol, stained with May-Gruenwald-Giemsa and mounted.
Evaluation criteria:
The test article was considered to induce a positive response if a dose-response increase in micronucleated polychromatic erythrocytes was observed and one or more doses were statistically elevated relative to the vehicle control.
If a single treatment group was significantly elevated at one sacrifice time with no evidence of a dose-response, the assay was considered equivocal and a repeat assay recommended.
The test article was considered negative if no statistically significant increase in micronucleated polychromatic erythrocytes above the concurrent vehicle control was observed at any sampling time.
Statistics:
Kastenbaum-Bowman Tables

Results and discussion

Test results
Key result
Sex:
male/female
Genotoxicity:
negative
Toxicity:
no effects
Remarks:
on bone marrow cells
Vehicle controls validity:
valid
Negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: No mutagenic potential
Additional information on results:
Lethargy observed at 300 mg/kg

Any other information on results incl. tables

Treatment (mg/kg)

Sex

Time

Number of mice

PCE/total erythrocytes (mean)

Change from control (%)

Micronucleated polychromatic erythrocytes

Number per 1000 PCEs (mean)

Number per PCEs scored (/10 000)

Sesame oil

M

24

5

0.46

-

0.6

6

 

F

24

5

0.46

-

0.5

5

75

M

24

5

0.37

-20

0.3

3

 

F

24

5

0.41

-11

0.5

5

150

M

24

5

0.42

-9

0.3

3

 

F

24

5

0.40

-13

0.4

4

300

M

24

5

0.35

-24

0.6

6

 

F

24

5

0.31

-33

0.4

4

CP (60)

M

24

5

0.38

-17

31.2

312*

 

F

24

5

0.27

-41

24.99

249*

MMC (2)

M

24

5

0.51

11

18.3

183*

 

F

24

5

0.49

7

18.4

184*

Sesame oil

M

48

5

0.48

-

0.5

5

 

F

48

5

0.44

-

0.5

5

75

M

48

5

0.59

23

0.5

5

 

F

48

5

0.46

5

0.4

4

150

M

48

5

0.46

-4

0..2

2

 

F

48

5

0.56

27

0.6

6

300

M

48

5

0.49

2

0.6

6

 

F

48

5

0.55

25

0.4

4

*p ≤0.05

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
4,4,7,7-Tetraethoxy-3,8-dioxa-4,7-disiladecane did not induce a significant increase in the incidence of micronucleated polychromatic erythrocytes in bone marrow of male and female ICR mice. It is concluded that the test substance is negative in the in vivo micronucleus test under the conditions of the test.