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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 January - 4 April, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report date:
1991

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Qualifier:
according to guideline
Guideline:
EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Constituent 1
Chemical structure
Reference substance name:
α-trimethylsilanyl-ω-trimethylsiloxypoly[oxy(methyl-3-(2-(2-methoxypropoxy)propoxy)propylsilanediyl]-co-oxy(dimethylsilane))
EC Number:
406-420-4
EC Name:
α-trimethylsilanyl-ω-trimethylsiloxypoly[oxy(methyl-3-(2-(2-methoxypropoxy)propoxy)propylsilanediyl]-co-oxy(dimethylsilane))
Cas Number:
69430-40-6
Molecular formula:
Unspecified example: C18.3H46.8O5.8Si4.1
IUPAC Name:
α-trimethylsilanyl-ω-trimethylsiloxypoly[oxy(methyl-3-(2-(2-methoxypropoxy)propoxy)propylsilanediyl]-co-oxy(dimethylsilane))
Details on test material:
Identification: DC 5067
Description: Clear, light brown liquid
Lot Number: AB 090122
Purity: >99%
Storage conditions: In the original container at room temperature in the dark
Stability under storage conditions: Stab1e
Expiry date: December 1, 1991

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
Single dosis
Frequency of treatment:
once (single dosis)
Post exposure period:
Bone marrow was sampled at 24, 48 and 72 hours after dosing.
Doses / concentrations
Remarks:
Doses / Concentrations:
5000 mg/kg body weight (10 ml per kg body weight)
Basis:
actual ingested
oral intubation
No. of animals per sex per dose:
Pilot study: 3 males and 3 females per dose (5000 and 3000 mg/kg body weight)
Micronucleus test: 5 males and 5 females per dose
Control animals:
yes, concurrent vehicle

Examinations

Tissues and cell types examined:
Bone marrow cells of the mouse.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not examined
Vehicle controls validity:
valid
Negative controls validity:
other: Corresponding vehicle treated groups served as negative controls.
Positive controls validity:
valid

Any other information on results incl. tables

Pilot study/Dose selection

In a preliminary study 12 animals (3 males and 3 females per group) were dosed orally with 5000 and 3000 mg/kg body weight (groups A and B, respectively). 1 The animals of group A and B initially showed lethargy (one animal of group 8 :. also showed piloerection) but recovered all within one day. Based on the results of this pilot study 5000 mg/kg body weight was selected as an appropriate dose for the Micronucleus Test.

Micronucleus Test

The mean number of micronuclei scored in the test substance-treated groups was compared with the corresponding control groups. No increase in the frequency of micronuclei was observed. The incidence of micronuclei in the control animals was found to be in the range of historical data (0.59 +- 0.89; mean + standard deviation, N = 1120). The groups that were treated with Cyclophosphamide stiowed a decrease in the ratio of polychromatic to normochromatic erythrocytes, which reflects a toxic effect of this compound on the erythropoiesis. The positive control substance induced in both sexes a statistically significant increase in the number of micronuclei.

It is concluded that this test is valid and that DC 5067 can be considered as not mutagenic in the Micronucleus Test under the experimental conditions described in this report.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative DC 5067 is not mutagenic in the Mouse.
It is concluded that this test is valid and that DC 5067 can be considered as not mutagenic in the Micronucleus Test under the experimental
conditions described in this report.
Executive summary:

DC 5067 was tested in the Micronucleus Test in mice. Three groups (A to F), each comprising 5 males and 5 females, received a single oral dose of 5000 mglkg body weight. Bone marrow was sampled at 24, 48 and 72 hours after dosing. Corresponding vehicle treated groups (A to C) served as negative controls. Bone marrow from a positive control group (G), treated with a single oral dose of cyclophosphamide (CP) at 50 mg/kg body weight, was harvested at 48 hours after dosing only, The test substance was found to respond negatively in the Micronucleus Test, whereas the positive control substance (CP) produced a statistically significant increase in the incidence of micronuclei in polychromatic erythrocytes.

It is concluded that DC 5067 can be considered as not mutagenic in the Mouse Micronucleus Test under the experimental conditions described in this report.